Classical Hodgkin lymphoma

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81 regimens on this page
128 variants on this page


Guidelines

ESMO

NCCN

Untreated, early-stage favorable

Definitions of favorable/unfavorable risk factors vary somewhat across sites; see original sources for details.

ABVD

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Example orders

Regimen

Study Evidence Comparator Efficacy
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) Phase III ABVD x 3 -> INRT Inconclusive whether non-inferior
Radford et al. 2015 (UK NCRI RAPID) Phase III ABVD x 3 -> IFRT Inconclusive whether non-inferior

Chemotherapy

4-week cycles, response adapted as follows:

  • Patients in EORTC/LYSA/FIL H10 received 2 cycles of ABVD followed by interim PET-CT:
    • Negative interim PET-CT (1 or 2 points on the 5-point Deauville scale): randomized to receive 2 more cycles of ABVD (4 cycles total) versus 1 more cycle of ABVD followed by INRT 30 Gy (+ 6 Gy boost)
    • Positive PET-CT: proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost)
  • Patients in UK NCRI RAPID received 3 cycles of ABVD followed by interim PET-CT:
    • Negative interim PET-CT (1 or 2 points on the 5-point Deauville scale): randomized to receive IFRT versus no further treatment (3 cycles total)
    • Positive interim PET-CT: proceeded to receive a fourth cycle of ABVD followed by IFRT.

References

  1. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article PubMed
  2. Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
  3. Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed

ABVD -> RT

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
RT: Radiation Therapy

Example orders

Regimen #1, ABVD x 2 -> IFRT

Study Evidence Comparator Efficacy
Engert et al. 2010 (GHSG HD10) Phase III ABVD x 4 -> IFRT Seems not superior
Behringer et al. 2014 (GHSG HD13) Phase III ABV -> IFRT Superior FFTF
AV -> IFRT Superior FFTF
AVD -> IFRT Might have superior FFTF

Chemotherapy

4-week cycle for 2 cycles, followed by IFRT (see individual protocols for details)

Regimen #2, ABVD x 3 -> IFRT

Study Evidence Comparator Efficacy
Radford et al. 2015 (UK NCRI RAPID) Phase III ABVD x 3 Inconclusive whether non-inferior

Chemotherapy

4-week cycle for 3 cycles, followed by IFRT (see note)

Note: Patients in UK NCRI RAPID received 3 cycles of ABVD followed by interim PET-CT; those with a negative PET-CT after the 3rd cycle (1 or 2 points on the 5-point Deauville scale) were randomized to receive IFRT versus no further treatment; those with a positive PET-CT proceeded to receive one more cycle of ABVD followed by IFRT.

Regimen #3, ABVD x 3 -> INRT

Study Evidence Comparator Efficacy
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) Phase III ABVD x 4 Inconclusive whether non-inferior

Chemotherapy

4-week cycle for 3 cycles, followed by INRT (see note)

Note: Patients in EORTC/LYSA/FIL H10 received 2 cycles of ABVD followed by interim PET-CT; those with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 2 more cycles of ABVD versus 1 more cycle of ABVD followed by INRT 30 Gy (+ 6 Gy boost); those with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost).

Regimen #4, ABVD x 4 -> IFRT

Study Evidence Comparator Efficacy
Bonadonna et al. 2004 Phase III ABVD x 4 -> STNI Seems not superior
Engert et al. 2010 (GHSG HD10) Phase III ABVD x 2 -> IFRT Seems not superior
Radford et al. 2015 (UK NCRI RAPID) Non-randomized portion of RCT

Note: Patients in UK NCRI RAPID received 3 cycles of ABVD followed by interim PET-CT; those with a positive PET-CT proceeded to receive a fourth cycle of ABVD followed by IFRT.

Chemotherapy

4-week cycle for 4 cycles, followed by IFRT (see individual protocols for details)

Regimen #5, ABVD x 2 -> EFRT

Study Evidence Comparator Efficacy
Engert et al. 2007 (GHSG HD7) Phase III EFRT Superior FFTF

Chemotherapy

4-week cycle for 2 cycles, followed by EFRT (30 Gy + 10 Gy to the involved field)

Regimen #6, ABVD x 4 -> STNI

Study Evidence Comparator Efficacy
Bonadonna et al. 2004 Phase III ABVD x 4 -> IFRT Seems not superior

Chemotherapy

4-week cycle for 4 cycles, followed by STNI

References

  1. Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004 Jul 15;22(14):2835-41. link to original article contains protocol PubMed
  2. Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10;25(23):3495-502. link to original article contains protocol PubMed
    1. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
  3. Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, Berger B, Greil R, Willborn KC, Wilhelm M, Debus J, Eble MJ, Sökler M, Ho A, Rank A, Ganser A, Trümper L, Bokemeyer C, Kirchner H, Schubert J, Král Z, Fuchs M, Müller-Hermelink HK, Müller RP, Diehl V. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12;363(7):640-52. link to original article PubMed
    1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.link to original article PubMed
    2. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
  4. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article PubMed
  5. Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
  6. Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Böll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015 Apr 11;385(9976):1418-27. Epub 2014 Dec 22. Erratum in: Lancet. 2015 Apr 11;385(9976):1396. link to original article PubMed
    1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.link to original article PubMed
  7. Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed

AVD -> IFRT

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AVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
IFRT: Involved Field Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Behringer et al. 2014 (GHSG HD13) Phase III ABV -> IFRT Not reported
ABVD -> IFRT Might have inferior FFTF
AV -> IFRT Not reported

Chemotherapy

4-week cycles

Chemotherapy is followed by IFRT.

References

  1. Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Böll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015 Apr 11;385(9976):1418-27. Epub 2014 Dec 22. Erratum in: Lancet. 2015 Apr 11;385(9976):1396. link to original article PubMed
    1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.link to original article PubMed

MOPP-ABV -> IFRT

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MOPP: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
ABV: Adriamycin (Doxorubicin), Bleomycin, Vinblastine
IFRT: Involved Field Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Fermé et al. 2007 (EORTC-GELA H8-F) Phase III Subtotal nodal radiotherapy Superior OS

Chemotherapy

4-week cycle for 3 cycles

Chemotherapy is followed in 3 to 4 weeks by IFRT; see text for details.

References

  1. Noordijk EM, Carde P, Dupouy N, Hagenbeek A, Krol AD, Kluin-Nelemans JC, Tirelli U, Monconduit M, Thomas J, Eghbali H, Aleman BM, Bosq J, Vovk M, Verschueren TA, Pény AM, Girinsky T, Raemaekers JM, Henry-Amar M. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. J Clin Oncol. 2006 Jul 1;24(19):3128-35. Epub 2006 Jun 5. link to original article PubMed
  2. Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains verified protocol in supplement PubMed

Stanford V -> RT

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RT: Radiation Therapy

Regimen

Study Evidence
Advani et al. 2013 (G4) Non-randomized

Chemotherapy

8-week course

Treatment followed in 1 to 3 weeks by modified IFRT.

References

  1. Advani RH, Hoppe RT, Baer D, Mason J, Warnke R, Allen J, Daadi S, Rosenberg SA, Horning SJ. Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial. Ann Oncol. 2013 Apr;24(4):1044-8. Epub 2012 Nov 7. contains limited protocol link to PMC article PubMed

Untreated, early-stage unfavorable

Definitions of favorable/unfavorable risk factors vary somewhat across sites; see original sources for details.

ABVD

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Example orders

Regimen

Study Evidence Comparator Efficacy
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) Phase III ABVD x 4 -> INRT Inconclusive whether non-inferior

Chemotherapy

4-week cycle for 2 cycles, then:

Patients with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 4 more cycles of ABVD versus 2 more cycles of ABVD followed by INRT 30 Gy (+ 6 Gy boost). Patients with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost).

References

  1. Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed

ABVD -> RT

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
RT: Radiation Therapy

Example orders

Regimen

Study Evidence Comparator Efficacy
Eich et al. 2010 (GHSG HD11) Phase III BEACOPP -> IFRT Seems not superior
von Tresckow et al. 2012 (GHSG HD14) Phase III BEACOPPesc x 2 -> ABVD x 2 -> IFRT Inferior FFTF
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10) Phase III ABVD x 6 Inconclusive whether noninferior
Advani et al. 2015 (ECOG E2496) Phase III Stanford V -> RT Seems not superior

Chemotherapy

4-week cycles, see note

Note: Patients in GHSG HD11 received 4 cycles of ABVD followed by randomization to 20 Gy versus 30 Gy of IFRT. Patients in GHSG HD14 received 4 cycles of ABVD followed by IFRT. Patients in EORTC/LYSA/FIL H10 received 2 cycles of ABVD followed by interim PET-CT; those with a negative interim PET-CT (1 or 2 points on the 5-point Deauville scale) were randomized to receive 4 more cycles of ABVD versus 2 more cycles of ABVD followed by INRT 30 Gy (+ 6 Gy boost); those with a positive PET-CT proceeded to receive escalated BEACOPP followed by INRT 30 Gy (+ 6 Gy boost). Patients in E2496 received 6 to 8 cycles of ABVD; all patients received 36 Gy IFRT to the mediastinum, hila, and supraclavicular regions two to three weeks after completion of chemotherapy.

References

  1. Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27):4199-206. Epub 2010 Aug 16. link to original article contains verified protocol PubMed
    1. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
  2. von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. link to original article contains verified protocol PubMed
  3. Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
  4. Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H Jr, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. J Clin Oncol. 2015 Jun 10;33(17):1936-42. Epub 2015 Apr 20. link to original article contains limited protocol link to PMC article PubMed

BEACOPP -> IFRT

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
IFRT: Involved Field Radiation Therapy

Example orders

Regimen

Study Evidence Comparator Efficacy
Eich et al. 2010 (GHSG HD11) Phase III ABVD -> IFRT Seems not superior

Chemotherapy

3-week cycle for 4 cycles

Patients were then randomized to receive 20 Gy versus 30 Gy of IFRT.

References

  1. Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27)99-206. Epub 2010 Aug 16. link to original article contains verified protocol PubMed
    1. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed

BEACOPP, escalated -> ABVD -> RT

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
von Tresckow et al. 2012 (GHSG HD14) Phase III ABVD x 4 -> IFRT Superior FFTF

Chemotherapy, escalated BEACOPP portion

Supportive medications

  • Filgrastim (Neupogen) (dose not specified) SC once per day starting on day 8, continues until ANC greater than 1000/uL for 3 consecutive days

3-week cycle for 2 cycles, followed by:

Chemotherapy, ABVD portion

4-week cycle for 2 cycles

Treatment was followed by radiation therapy to the involved fields.

References

  1. von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. link to original article contains verified protocol PubMed

BV + AVD -> ISRT

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BV + AVD: Brentuximab Vedotin, Adriamycin (Doxorubicin), Vinblastine, Dacarbazine
ISRT: Involved Site Radiation Therapy

Regimen

Study Evidence
Kumar et al. 2016 Phase II

Chemotherapy

4-week cycle for 4 cycles

Chemotherapy is followed by repeat PET-CT; patients with a negative PET-CT proceeded to receive 30 Gy of ISRT.

References

  1. Kumar A, Casulo C, Yahalom J, Schöder H, Barr PM, Caron P, Chiu A, Constine LS, Drullinsky P, Friedberg JW, Gerecitano JF, Hamilton A, Hamlin PA, Horwitz SM, Jacob AG, Matasar MJ, McArthur GN, McCall SJ, Moskowitz AJ, Noy A, Palomba ML, Portlock CS, Straus DJ, VanderEls N, Verwys SL, Yang J, Younes A, Zelenetz AD, Zhang Z, Moskowitz CH. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood. 2016 Sep 15;128(11):1458-64. Epub 2016 Jul 25. link to original article contains verified protocol link to PMC article PubMed

MOPP-ABV -> IFRT

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MOPP: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
ABV: Adriamycin (Doxorubicin), Bleomycin, Vinblastine
IFRT: Involved Field Radiation Therapy

Regimen #1

Study Evidence Comparator Efficacy
Fermé et al. 2007 (EORTC-GELA H8-U) Phase III MOPP-ABV x 6 -> IFRT Seems not superior
MOPP-ABV x 4 -> STNI Seems not superior

Chemotherapy

4-week cycle for 4 cycles

Chemotherapy is followed in 3 to 4 weeks by IFRT; see text for details.

Regimen #2

Study Evidence Comparator Efficacy
Fermé et al. 2007 (EORTC-GELA H8-U) Phase III MOPP-ABV x 4 -> IFRT Seems not superior
MOPP-ABV x 4 -> STNI Seems not superior

Chemotherapy

4-week cycle for 6 cycles

Chemotherapy is followed in 3 to 4 weeks by IFRT; see text for details.

References

  1. Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains verified protocol in supplement PubMed

Stanford V -> RT

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Advani et al. 2015 (E2496) Phase III ABVD -> RT Seems not superior

In Advani et al. 2015 the Stanford V regimen is described as "once per week for 12 weeks." However, the regimen has previously been described as being 4-week cycles for 3 cycles (same duration, but schedule is different). Until this discrepancy is resolved, we replicate the 4-week cycle version here:

Chemotherapy

4-week cycle for 3 cycles

All patients received 36 Gy IFRT to the mediastinum, hila, and supraclavicular regions two to three weeks after completion of chemotherapy, with additional IFRT to additional sites greater than or equal to 5 cm (details not described).

References

  1. Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H Jr, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. J Clin Oncol. 2015 Jun 10;33(17):1936-42. Epub 2015 Apr 20. link to original article contains limited protocol link to PMC article PubMed

Untreated, advanced stage

Generally defined as stage III/IV or stage II with bulky disease. Definitions for bulky disease vary across sites; see original sources for details,

ABVD

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Example orders

Regimen #1, PET-adapted

Study Evidence
Zinzani et al. 2016 (HD0801) Non-randomized
Press et al. 2016 (SWOG S0816) Phase II
Johnson et al. 2016 (RATHL) Non-randomized portion of RCT

Chemotherapy

4-week cycle for 2 cycles, followed by:

  • HD0801: Patients underwent interim PET-CT after 2 cycles; those with a negative PET-CT by Juweid's criteria received 4 more cycles of ABVD (6 total) and those with initial bulky disease were then randomized to RT versus no further treatment. Those with a positive PET-CT by Juweid's criteria proceeded to salvage IGEV.
  • SWOG S0816: Patients underwent interim PET-CT after 2 cycles; those with a negative PET-CT by Deauville score (1 to 3) received 4 more cycles of ABVD (6 total); those with a positive PET-CT by Deauville score (4 or 5) proceeded to salvage escalated BEACOPP.
  • RATHL: Patients underwent interim PET-CT after 2 cycles; those with a negative PET-CT by Deauville score (1 to 3) were randomized to 4 more cycles of ABVD (6 total) versus 4 cycles of AVD; those with a positive PET-CT by Deauville score (4 or 5) proceeded to salvage escalated BEACOPP or salvage BEACOPP-14, specified in advance.

Regimen #2, 8 cycles (ABVD8)

Study Evidence Comparator Efficacy
Bonadonna et al. 1975 Phase III MOPP Seems not superior
Santoro et al. 1987 Phase III MOPP Seems to have superior OS
Canellos et al. 1992 Phase III MOPP Superior FFS
MOPP/ABVD Not reported
Hoskin et al. 2009 (UK NCRI ISRCTN 64141244) Phase III Stanford V Seems not superior
Viviani et al. 2011 Phase III BEACOPP4+4 Seems to have inferior FFFP
Gordon et al. 2013 (E2496) Phase III Stanford V Seems not superior
Mounier et al. 2014 (LYSA H34) Phase III BEACOPP4+4 Might have inferior EFS
Carde et al. 2016 (EORTC 20012) Phase III BEACOPP4+4 Seems not superior

Chemotherapy

4-week cycle for 8 cycles

References

  1. Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975 Jul;36(1):252-9. PubMed
  2. Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F, et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
  3. Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. link to original article PubMed
  4. Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM, Canellos GP, Peterson BA. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003 Feb 15;21(4):607-14. link to original article PubMed
  5. Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, MacLennan KA, Stenning SP, Clawson S, Smith P, Ryder D, Hancock BW; United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20;23(36):9208-18. Epub 2005 Nov 28. link to original article PubMed
  6. Hoskin PJ, Lowry L, Horwich A, Jack A, Mead B, Hancock BW, Smith P, Qian W, Patrick P, Popova B, Pettitt A, Cunningham D, Pettengell R, Sweetenham J, Linch D, Johnson PW. Randomized comparison of the stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009 Nov 10;27(32):5390-6. Epub 2009 Sep 8. link to original article PubMed
  7. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
  8. Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article link to PMC article PubMed
    1. Subgroup analysis: Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Gospodarowicz M, Cheson BD, Stiff PJ, Advani R, Miller TP, Hoppe RT, Kahl BS, Horning SJ. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013 Apr;161(1):76-86. Epub 2013 Jan 29. link to PMC article PubMed
  9. Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles =4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
  10. Zinzani PL, Broccoli A, Gioia DM, Castagnoli A, Ciccone G, Evangelista A, Santoro A, Ricardi U, Bonfichi M, Brusamolino E, Rossi G, Anastasia A, Zaja F, Vitolo U, Pavone V, Pulsoni A, Rigacci L, Gaidano G, Stelitano C, Salvi F, Rusconi C, Tani M, Freilone R, Pregno P, Borsatti E, Sacchetti GM, Argnani L, Levis A. Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study. J Clin Oncol. 2016 Apr 20;34(12):1376-85. Epub 2016 Feb 16. link to original article contains verified protocol PubMed
  11. Press OW, Li H, Schöder H, Straus DJ, Moskowitz CH, LeBlanc M, Rimsza LM, Bartlett NL, Evens AM, Mittra ES, LaCasce AS, Sweetenham JW, Barr PM, Fanale MA, Knopp MV, Noy A, Hsi ED, Cook JR, Lechowicz MJ, Gascoyne RD, Leonard JP, Kahl BS, Cheson BD, Fisher RI, Friedberg JW. US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816. J Clin Oncol. 2016 Jun 10;34(17):2020-7. Epub 2016 Apr 11. link to original article contains verified protocol link to PMC article PubMed
  12. Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. link to original article contains verified protocol PubMed
  13. Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed

ABVD, DD-DI

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ABVD, DD-DI: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine, Dose-Dense and Dose-Intense

Regimen

Study Evidence
Russo et al. 2014 Phase II

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. Russo F, Corazzelli G, Frigeri F, Capobianco G, Aloj L, Volzone F, De Chiara A, Bonelli A, Gatani T, Marcacci G, Donnarumma D, Becchimanzi C, de Lutio E, Ionna F, De Filippi R, Lastoria S, Pinto A. A phase II study of dose-dense and dose-intense ABVD (ABVD(DD-DI) ) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma. Br J Haematol. 2014 Jul;166(1):118-29. Epub 2014 Mar 27. link to original article contains verified protocol PubMed

AVD

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AVD: Adriamycin (Doxorubicin), Vinblastine, Dacarbazine

Regimen

Study Evidence Comparator Efficacy
Johnson et al. 2016 (RATHL) Phase III ABVD Inconclusive whether non-inferior

Treatment preceded by ABVD x 2.

Chemotherapy

4-week cycle for 4 cycles

References

  1. Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed

BEACOPP

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Example orders

Regimen

Study Evidence Comparator Efficacy
Diehl et al. 1997 Non-randomized
Diehl et al. 1998 (GHSG HD9) Phase III Escalated dose BEACOPP Inferior FFTF
COPP-ABVD Seems to have superior OS
Ballova et al. 2005 (GHSG HD9elderly) Phase III COPP-ABVD Seems not superior

Note that this is technically "BEACOPP II." The original "BEACOPP I" is detailed in Diehl et al. 1997 but is of historical interest, only.

Chemotherapy

3-week cycle for 8 cycles

References

  1. Diehl V, Sieber M, Rüffer U, Lathan B, Hasenclever D, Pfreundschuh M, Loeffler M, Lieberz D, Koch P, Adler M, Tesch H. BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin's disease. The German Hodgkin's Lymphoma Study Group. Ann Oncol. 1997 Feb;8(2):143-8. link to original article contains verified protocol PubMed
  2. Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains verified protocol PubMed
    1. Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains protocol PubMed
    2. Update: Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. link to original article PubMed
  3. Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. link to original articlecontains protocol PubMed

BEACOPP-14

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BEACOPP-14: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone, 14-day course

Regimen

Study Evidence Comparator Efficacy
Sieber et al. 2003 Phase II
Engert et al. 2012 (GHSG HD15) Phase III Escalated BEACOPP x 8 Not reported
Escalated BEACOPP x 6 Non-inferior FFTF

Chemotherapy

Supportive medications

  • Filgrastim (Neupogen) as follows:
    • <75 kg body weight: 300 mcg SC once per day on days 8 to 13
    • greater than or equal to 75 kg body weight: 480 mcg SC once per day on days 8 to 13

2-week cycle for 8 cycles

References

  1. Sieber M, Bredenfeld H, Josting A, Reineke T, Rueffer U, Koch T, Naumann R, Boissevain F, Koch P, Worst P, Soekler M, Eich H, Müller-Hermelink HK, Franklin J, Paulus U, Wolf J, Engert A, Diehl V; German Hodgkin's Lymphoma Study Group. 14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 May 1;21(9):1734-9. link to original article contains verified protocol PubMed
  2. Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, Zijlstra J, Král Z, Fuchs M, Hallek M, Kanz L, Döhner H, Dörken B, Engel N, Topp M, Klutmann S, Amthauer H, Bockisch A, Kluge R, Kratochwil C, Schober O, Greil R, Andreesen R, Kneba M, Pfreundschuh M, Stein H, Eich HT, Müller RP, Dietlein M, Borchmann P, Diehl V; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12;379(9828):1791-9. Epub 2012 Apr 4. Erratum in: Lancet. 2012 May 12;379(9828):1790. link to original article PubMed

BEACOPP, escalated -> BEACOPP

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study Evidence Comparator Efficacy
Viviani et al. 2011 Phase III ABVD Seems to have superior FFFP
Borchmann et al. 2011 (GHSG HD12) Phase III Escalated BEACOPP Inferior early progressive disease rate
Mounier et al. 2014 (LYSA H34) Phase III ABVD Might have superior EFS
Carde et al. 2016 (EORTC 20012) Phase III ABVD8 Seems not superior

Frequently referred to as BEACOPPescalated -> BEACOPPbaseline or BEACOPP4+4.

Escalated portion

Supportive medications

  • Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC greater than 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (Mounier et al. 2014)

3-week cycle for 4 cycles, followed by:

Standard portion

Supportive medications

  • Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC greater than 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (Mounier et al. 2014)

3-week cycle for 4 cycles

References

  1. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
  2. Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
  3. Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles =4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
  4. Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. link to original article contains verified protocol PubMed

BEACOPP, escalated dose

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Example orders

Regimen #1, 6 cycles

Study Evidence Comparator Efficacy
Engert et al. 2012 (GHSG HD15) Phase III BEACOPP-14 Non-inferior FFTF
Escalated BEACOPP x 8 Seems to have superior OS

Details are not available in the abstract; it is assumed that the regimen is identical to escalated BEACOPP x 8, with 2 fewer cycles.

Chemotherapy

3-week cycle for 6 cycles

Regimen #2, 8 cycles

Study Evidence Comparator Efficacy
Diehl et al. 1998 (GHSG HD9) Phase III BEACOPP Superior FFTF
COPP-ABVD Seems to have superior OS
Borchmann et al. 2011 (GHSG HD12) Phase III Escalated BEACOPP -> BEACOPP Superior early progressive disease rate
Engert et al. 2012 (GHSG HD15) Phase III BEACOPP-14 Not reported
Escalated BEACOPP x 6 Seems to have inferior OS
Borchmann et al. 2017 (GHSG HD18) Phase III R-BEACOPPescalated Seems not superior

Note: all patients in GHSG HD18 received 2 cycles of BEACOPPescalated and were PET-positive at time of randomization.

Chemotherapy

3-week cycle for 8 cycles

References

  1. Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains verified protocol PubMed
    1. Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains protocol PubMed
    2. Update: Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. link to original article PubMed
  2. Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
  3. Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, Zijlstra J, Král Z, Fuchs M, Hallek M, Kanz L, Döhner H, Dörken B, Engel N, Topp M, Klutmann S, Amthauer H, Bockisch A, Kluge R, Kratochwil C, Schober O, Greil R, Andreesen R, Kneba M, Pfreundschuh M, Stein H, Eich HT, Müller RP, Dietlein M, Borchmann P, Diehl V; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12;379(9828):1791-9. Epub 2012 Apr 4. Erratum in: Lancet. 2012 May 12;379(9828):1790. link to original article PubMed
  4. Borchmann P, Haverkamp H, Lohri A, Mey U, Kreissl S, Greil R, Markova J, Feuring-Buske M, Meissner J, Dührsen U, Ostermann H, Keller U, Maschmeyer G, Kuhnert G, Dietlein M, Kobe C, Eich H, Baues C, Stein H, Fuchs M, Diehl V, Engert A. Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPP(escalated) alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group. Lancet Oncol. 2017 Apr;18(4):454-463. Epub 2017 Feb 22. link to original article PubMed

B-AVD; AVD-A

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B-AVD: Brentuximab vedotin, Adriamycin (Doxorubicin), Vinblastine, Dacarbazine
AVD-A: Adriamycin (Doxorubicin), Vinblastine, Dacarbazine, Adcetris (Brentuximab vedotin),

Regimen

Study Evidence
Younes et al. 2013 Non-randomized

This was a phase I trial but had greater than 20 patients in the MTD expansion cohort; a phase III trial is underway.

Chemotherapy

4-week cycle for up to 6 cycles

"Consolidative radiotherapy was permitted at the investigator's discretion."

References

  1. Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. Epub 2013 Nov 15. link to original article contains verified protocol PubMed
    1. Update: Abstract: Joseph M Connors, MD, Stephen Ansell, Steven I. Park, MD, Michelle A. Fanale, M.D. and Anas Younes. Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes. ASH Annual Meeting 2014, Abstract 292 link to abstract

C-MOPP/ABV

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C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
ABV: Adriamycin (Doxorubicin), Bleomycin, Vinblastine

Regimen

Study Evidence
Montoto et al. 2000 Phase II

Chemotherapy

4-week cycle for 8 cycles

  • 25 to 40 Gy of radiation therapy given over extended fields (mantle or inverted "Y" type) to patients with bulky disease or ones with residual disease after completion of chemotherapy

References

  1. Montoto S, Camós M, López-Guillermo A, Bosch F, Cervantes F, Blandé J, Esteve J, Cobo F, Nomdedeu B, Campo E, Montserrat E. Hybrid chemotherapy consisting of cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) as first-line treatment for patients with advanced Hodgkin disease. Cancer. 2000 May 1;88(9):2142-8. link to original article contains protocol PubMed]

COPP-ABVD, C-MOPP/ABVD

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COPP: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

Study Evidence Comparator Efficacy
Diehl et al. 1998 (GHSG HD9) Phase III BEACOPP
Escalated dose BEACOPP 		Seems to have inferior OS
Takenaka et al. 2000 (JCOG 8905) Phase II
Ballova et al. 2005 (GHSG HD9elderly) Phase III BEACOPP Seems not superior

Chemotherapy, COPP portion

4-week cycle for 5 total cycles of C-MOPP, alternating with 5 total cycles of ABVD

Chemotherapy, ABVD portion

4-week cycle for 5 total cycles of ABVD, alternating with 5 total cycles of C-MOPP

  • 30 Gy of involved field radiation after completion of chemotherapy was given to patients with bulky (=10 cm maximum diameter) disease

Dose modifications

  • Treatment was postponed for at least 1 week or until recovery if:
    • Pretreatment ANC was less than 1500/uL
    • Platelet count was less than 100 x 109/L
    • AST/S-GOT was greater than 100 IU/L
    • Total bilirubin was greater than 2
  • Vincristine (Oncovin) and Vinblastine (Velban) were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)
  • Doxorubicin (Adriamycin) was discontinued if cardiac LV ejection fraction was less than 50%
  • Bleomycin (Blenoxane) was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement
  • Note: Dacarbazine (DTIC) 250 mg/m2 was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with Dacarbazine (DTIC) 375 mg/m2.

References

  1. Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains verified protocol PubMed
    1. Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains protocol PubMed
  2. Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group. Jpn J Clin Oncol. 2000 Mar;30(3):146-52. link to original article contains protocol PubMed
  3. Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V; German Hodgkin's Lymphoma Study Group. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 Oct 1;21(19):3601-8. Epub 2003 Aug 11. link to original article PubMed
    1. Update: Sasse S, Klimm B, Görgen H, Fuchs M, Heyden-Honerkamp A, Lohri A, Koch O, Wilhelm M, Trenn G, Finke J, Müller RP, Diehl V, Eich HT, Borchmann P, Engert A; German Hodgkin Study Group (GHSG). Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012 Nov;23(11):2953-9. Epub 2012 Jul 5. link to original article PubMed
    2. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
  4. Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. link to original articlecontains protocol PubMed

MOPP

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MOPP: Mechlorethamine, Oncovin (Vincristine), Procarbazine, Prednisone

Example orders

Regimen

Study Evidence Comparator Efficacy
Devita et al. 1970 Phase II
Bonadonna et al. 1975 Phase III ABVD Seems not superior
Cooper et al. 1980 Phase III COPP Seems not superior
CVPP Seems to have inferior CR rate
MVPP Seems not superior
Santoro et al. 1982 Phase III MOPP/ABVD Inferior PFS
Santoro et al. 1987 Phase III ABVD Seems to have inferior OS
Longo et al. 1991 Phase III MOPP/CABS Seems not superior
Canellos et al. 1992 Phase III ABVD Inferior FFS
MOPP/ABVD Seems to have inferior FFS
Somers et al. 1994 Phase III MOPP/ABVD Seems to have inferior FFS

Chemotherapy

4-week cycle for 6 cycles

References

  1. Devita VT Jr, Serpick AA, Carbone PP. Combination chemotherapy in the treatment of advanced Hodgkin's disease. Ann Intern Med. 1970 Dec;73(6):881-95. link to original article contains protocol PubMed content property of HemOnc.org
  2. Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975 Jul;36(1):252-9. link to original article PubMed
  3. Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. link to original article PubMed
  4. Santoro A, Bonadonna G, Bonfante V, Valagussa P. Alternating drug combinations in the treatment of advanced Hodgkin's disease. N Engl J Med. 1982 Apr 1;306(13):770-5. link to original article PubMed
    1. Update: Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease. A report of 8-year results. Ann Intern Med. 1986 Jun;104(6):739-46. link to original article PubMed
  5. Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F, et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
  6. Longo DL, Duffey PL, DeVita VT Jr, Wiernik PH, Hubbard SM, Phares JC, Bastian AW, Jaffe ES, Young RC. Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP. J Clin Oncol. 1991 Aug;9(8):1409-20. link to original article PubMed
  7. Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. link to original article PubMed
  8. Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, et al. A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol. 1994 Feb;12(2):279-87. link to original article PubMed

MOPP/ABV

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MOPP: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
ABV: Adriamycin (Doxorubicin), Bleomycin, Vinblastine

Regimen

Study Evidence Comparator Efficacy
Klimo et al. 1985 Phase II
Glick et al. 1998 Phase III MOPP -> ABVD Seems to have superior OS
Duggan et al. 2003 Phase III ABVD Seems not superior

Chemotherapy

4-week cycle for 6 to 8 cycles

References

  1. Klimo P, Connors JM. MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin's disease. J Clin Oncol. 1985 Sep;3(9):1174-82. link to original article contains verified protocol PubMed
  2. Glick JH, Young ML, Harrington D, Schilsky RL, Beck T, Neiman R, Fisher RI, Peterson BA, Oken MM. MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial. J Clin Oncol. 1998 Jan;16(1):19-26. link to original article PubMed
  3. Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM, Canellos GP, Peterson BA. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003 Feb 15;21(4):607-14. link to original article PubMed

MOPP/ABVD

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MOPP/ABVD: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone alternating with Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

Study Evidence Comparator Efficacy
Santoro et al. 1982 Phase III MOPP Superior PFS
Canellos et al. 1992 Phase III ABVD Not reported
MOPP Seems to have superior FFS
Somers et al. 1994 Phase III MOPP Seems to have superior FFS

To be completed

References

  1. Santoro A, Bonadonna G, Bonfante V, Valagussa P. Alternating drug combinations in the treatment of advanced Hodgkin's disease. N Engl J Med. 1982 Apr 1;306(13):770-5. link to original article PubMed
    1. Update: Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease. A report of 8-year results. Ann Intern Med. 1986 Jun;104(6):739-46. link to original article PubMed
  2. Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. link to original article PubMed
  3. Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, et al. A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol. 1994 Feb;12(2):279-87. link to original article PubMed
  4. Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L, Soncini F, Valagussa P. Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results. J Clin Oncol. 1996 May;14(5):1421-30. link to original article PubMed
  5. Connors JM, Klimo P, Adams G, Burns BF, Cooper I, Meyer RM, O'Reilly SE, Pater J, Quirt I, Sadura A, Shustik C, Skillings J, Sutcliffe S, Verma S, Yoshida S, Zee B. Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 1997 Apr;15(4):1638-45. Erratum in: J Clin Oncol 1997 Jul;15(7):2762. link to original article PubMed

MOPP/ABVD -> RT

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MOPP: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
RT: Radiation Therapy

Regimen

Study Evidence
Salvagno et al. 1995 Phase II

To be completed

References

  1. Salvagno L, Sorarù M, Sotti G, Aversa S, Chiarion Sileni V, Mazzarotto R, Scarzello G, Bianco A, Pappagallo GL, Fiorentino MV. Hybrid MOPP/ABVD and radiotherapy in advanced Hodgkin's disease. Ann Oncol. 1995 Feb;6(2):173-9. link to original article PubMed
  2. Longo DL, Glatstein E, Duffey PL, Young RC, Ihde DC, Bastian AW, Wilson WH, Wittes RE, Jaffe ES, Hubbard SM, DeVita VT Jr. Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease. J Clin Oncol. 1997 Nov;15(11):3338-46. link to original article PubMed

PVAG

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PVAG: Prednisone, Vinblastine, Adriamycin (Doxorubicin), Gemcitabine

Regimen

Study Evidence
Böll et al. 2011 Phase II

This regimen is intended for elderly patients and was also open to patients with early unfavorable disease, but 93% of patients on study had advanced disease.

Chemotherapy

3-week cycle for 6 to 8 cycles

Patients with PR at the end of treatment underwent 30 Gy of radiotherapy.

References

  1. Böll B, Bredenfeld H, Görgen H, Halbsguth T, Eich HT, Soekler M, Markova J, Keller U, Graeven U, Kremers S, Geissler M, Trenn G, Fuchs M, von Tresckow B, Eichenauer DA, Borchmann P, Engert A. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011 Dec 8;118(24):6292-8. Epub 2011 Sep 13. link to original article contains verified protocol PubMed

Stanford V

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Regimen

Study Evidence Comparator Efficacy
Hoskin et al. 2009 (UK NCRI ISRCTN 64141244) Phase III ABVD Seems not superior
Gordon et al. 2013 (ECOG E2496) Phase III ABVD Seems not superior

Chemotherapy

Supportive medications

  • If dose reduction or delay occurred at any time during chemotherapy, Filgrastim (Neupogen) 5 mcg/kg SC once per day x 5 days (starting 48 hours after myelosuppressive chemotherapy) should be given after all subsequent day 1 and 15 doses of chemotherapy. It was not precisely specified when to discontinue Filgrastim (Neupogen).
  • Ranitidine (Zantac) 150 mg PO BID throughout the course of treatment
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID throughout the course of treatment
  • Acyclovir (Zovirax) 200 mg PO TID throughout the course of treatment
  • Ketoconazole (Nizoral) 200 mg PO once per day throughout the course of treatment; note: this may be optional--Horning SJ et al. J Clin Oncol (2000) listed this as a prophylactic medication, but Horning SJ et al. J Clin Oncol (2002) did not list this when prophylactic medications were specifically listed.

4-week cycle for 3 cycles

  • 36 Gy of consolidative radiation (1.8 Gy in 20 fractions) is started 2 to 4 weeks after chemotherapy is complete and is given to sites of disease greater than or equal to 5 cm and/or to macroscopic nodules in the spleen.

Dose reductions and delayed treatment:

References

  1. Bartlett NL, Rosenberg SA, Hoppe RT, Hancock SL, Horning SJ. Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report. J Clin Oncol. 1995 May;13(5):1080-8. link to original article PubMed
    1. Update: Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002 Feb 1;20(3):630-7. link to original article PubMed
  2. Horning SJ, Williams J, Bartlett NL, Bennett JM, Hoppe RT, Neuberg D, Cassileth P. Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492. J Clin Oncol. 2000 Mar;18(5):972-80. link to original article PubMed
  3. Hoskin PJ, Lowry L, Horwich A, Jack A, Mead B, Hancock BW, Smith P, Qian W, Patrick P, Popova B, Pettitt A, Cunningham D, Pettengell R, Sweetenham J, Linch D, Johnson PW. Randomized comparison of the stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009 Nov 10;27(32):5390-6. Epub 2009 Sep 8. link to original article PubMed
  4. Edwards-Bennett SM, Jacks LM, Moskowitz CH, Wu EJ, Zhang Z, Noy A, Portlock CS, Straus DJ, Zelenetz AD, Yahalom J. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010 Mar;21(3):574-81. link to original article PubMed
  5. Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article link to PMC article PubMed
    1. Subgroup analysis: Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Gospodarowicz M, Cheson BD, Stiff PJ, Advani R, Miller TP, Hoppe RT, Kahl BS, Horning SJ. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013 Apr;161(1):76-86. Epub 2013 Jan 29. link to PMC article PubMed

VEBEP

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VEBEP: Vepesid (Etoposide), Epirubicin, Bleomycin, Endoxan (Cyclophosphamide), Prednisolone

Regimen

Study Evidence
Viviani et al. 1999 Phase II

To be completed

References

  1. Viviani S, Bonfante V, Santoro A, Zanini M, Devizzi L, Di Russo AD, Soncini F, Villani F, Ragni G, Valagussa P, Bonadonna G. Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease. Cancer J Sci Am. 1999 Sep-Oct;5(5):275-82. PubMed
  2. Picardi M, De Renzo A, Pane F, Nicolai E, Pacelli R, Salvatore M, Rotoli B. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans. Leuk Lymphoma. 2007 Sep;48(9):1721-7. link to original article PubMed

Untreated

These regimens are not targeted to a particular subgroup of untreated Hodgkin lymphoma.

ABVD

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ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

To be moved to the appropriate indication, see above

4-week cycle for 4 to 6 cycles based on stage, response, and whether radiation therapy is used.

References

  1. Bonadonna G, Santoro A. ABVD chemotherapy in the treatment of Hodgkin's disease. Cancer Treat Rev. 1982 Mar;9(1):21-35. (no link to original article available) PubMed
  2. Bonadonna G. Chemotherapy strategies to improve the control of Hodgkin's disease: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1982 Nov;42(11):4309-20. link to original article contains protocol PubMed
  3. Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
  4. Carde P, Hagenbeek A, Hayat M, Monconduit M, Thomas J, Burgers MJ, Noordijk EM, Tanguy A, Meerwaldt JH, Le Fur R et al. Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol. 1993 Nov;11(11):2258-72. link to original article PubMed
  5. Retrospective: Stamatoullas A, Brice P, Bouabdallah R, Mareschal S, Camus V, Rahal I, Franchi P, Lanic H, Tilly H. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol. 2015 Jul;170(2):179-84. Epub 2015 Apr 19. link to original article PubMed

ABVE-PC

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ABVE-PC: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide

Regimen

Study Evidence
Schwartz et al. 2009 (COG P9425) Phase II
Friedman et al. 2014 (AHOD0031) Non-randomized portion of RCT

This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin is referred to as being given at a dose of 5 IU/m2 after amendment in P9425 but unclear if this is for cycle 1 only.

Chemotherapy

21-day cycles

References

  1. Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 link to original article contains verified protocol link to PMC article PubMed
  2. Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. link to original article contains protocol link to PMC article PubMed

Brentuximab vedotin (Adcetris)

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Regimen

Study Evidence
Forero-Torres et al. 2015 Phase II

Chemotherapy

  • Brentuximab vedotin (Adcetris) as follows:
    • eGFR greater than or equal to 30: 1.8 mg/kg IV once on day 1
      • Dose reduction to 1.2 mg/kg and treatment delay up to 3 weeks allowed for toxicities
    • eGFR less than 30: 1.2 mg/kg IV once on day 1

Supportive medications

  • "according to institutional standards"

21-day cycle for up to 16 cycles, with continuing treatment allowed for those deriving clinical benefit

References

  1. Forero-Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV, Bordoni RE, Friedberg JW, Sharman JP, Palanca-Wessels MC, Wang Y, Yasenchak CA. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015 Dec 24;126(26):2798-804. Epub 2015 Sep 16. link to original article contains verified protocol link to PMC article PubMed

BV-ABVD

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BV-ABVD: Brentuximab Vedotin, Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

Study Evidence
Federico et al. 2014 Phase II, <20 patients reported

Brentuximab vedotin portion

3-week cycle for 2 cycles, followed by:

ABVD portion

4-week cycle for 3 to 6 cycles based on stage, +/- radiation therapy

References

  1. Abstract: Massimo Federico, Emanuela Anna Pesce, Francesco Merli, Stefano Luminari, Stephane Chauvie, Cinzia Pellegrini, Luigi Marcheselli, Isabella Capodanno, Fiorella Ilariucci, Massimiliano Salati, Lisa Argnani, Pier Luigi Zinzani. A pilot phase II study with brentuximab vedotin followed by ABVD in patients with previously untreated Hodgkin lymphoma: A preliminary report. J Clin Oncol 32:5s, 2014 (suppl; abstr 8507) link to original abstract

ChlVPP

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ChlVPP: Chllorambucil, Vinblastine, Procarbazine, Prednisone

Regimen

Study Evidence
International ChIVPP Treatment Group 1995 Phase II

Chemotherapy

4-week cycle to complete remission plus 2 cycles; minimum of 6 cycles and maximum of 8 cycles

References

  1. Retrospective: Druker BJ, Rosenthal DS, Canellos GP. Chlorambucil, vinblastine, procarbazine, and prednisone. An effective but less toxic regimen than MOPP for advanced-stage Hodgkin's disease. Cancer. 1989 Mar 15;63(6):1060-4. link to original article PubMed
  2. Selby P, Patel P, Milan S, Meldrum M, Mansi J, Mbidde E, Brada M, Perren T, Forgeson G, Gore M, et al. ChlVPP combination chemotherapy for Hodgkin's disease: long-term results. Br J Cancer. 1990 Aug;62(2):279-85. link to PMC article PubMed
  3. The International ChlVPP Treatment Group. ChlVPP therapy for Hodgkin's disease: experience of 960 patients. Ann Oncol. 1995 Feb;6(2):167-72. link to original article contains protocol PubMed

OEPA -> COPDAC

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OEPA -> COPDAC: Oncovin (Vincristine), Bleomycin, Prednisone, Adriamycin (Doxorubicin) followed by Cyclophosphamide, Oncovin (Vincristine), Prednisone, DACarbazine

Regimen

Study Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) Phase II

This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.

OEPA portion

28-day cycle for 2 cycles, followed by:

COPDAC portion

28-day cycle for 2 to 4 cycles, depending on treatment group

References

  1. Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. link to original article contains verified protocol PubMed

OPPA -> COPP

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OPPA: Oncovin (Vincristine), Procarbazine, Prednisone, Adriamycin (Doxorubicin)
COPP: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Procarbazine

Regimen

Study Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) Phase II

This regimen is meant for girls. Patients with early-stage disease only received the OEPA portion, see text for details.

OPPA portion

28-day cycle for 2 cycles, followed by:

COPP portion

28-day cycle for 2 to 4 cycles, depending on treatment group

References

  1. Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. link to original article contains verified protocol PubMed

RABVD

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RABVD: Rituximab, Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen #1

Study Evidence
Younes et al. 2012 Phase II

Chemotherapy

28-day cycle for 6 cycles (except rituximab, which is given for a total of 6 doses)

Regimen #2

Study Evidence
Kasamon et al. 2012 Phase II

Chemotherapy

28-day cycle for 6 to 8 cycles

References

  1. Younes A, Oki Y, McLaughlin P, Copeland AR, Goy A, Pro B, Feng L, Yuan Y, Chuang HH, Macapinlac HA, Hagemeister F, Romaguera J, Samaniego F, Fanale MA, Dabaja BS, Rodriguez MA, Dang N, Kwak LW, Neelapu SS, Fayad LE. Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4123-8. Epub 2012 Feb 27. link to original article contains protocol link to PMC article PubMed
  2. Kasamon YL, Jacene HA, Gocke CD, Swinnen LJ, Gladstone DE, Perkins B, Link BK, Popplewell LL, Habermann TM, Herman JM, Matsui WH, Jones RJ, Ambinder RF. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4129-32. Epub 2012 Feb 16. link to original article contains partial protocol link to PMC article PubMed

VEPEMB

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VEPEMB: Vinblastine, Endoxan (Cyclophosphamide), Procarbazine, Etoposide, Mitoxantrone, Bleomycin

Regimen

Study Evidence Comparator Efficacy
Levis et al. 2004 Phase II
Zallio et al. 2016 Phase III ABVD Might have inferior PFS

This regimen is intended for elderly patients.

To be completed (?)

References

  1. Levis A, Anselmo AP, Ambrosetti A, Adamo F, Bertini M, Cavalieri E, Gavarotti P, Genua A, Liberati M, Pavone V, Pietrasanta D, Ricetti MM, Scalabrini DR, Salvi F, Vitolo U, Angelucci E, Boccadoro M, Gallo E, Mandelli F; Intergruppo Italiano Linfomi (IIL). VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study. Ann Oncol. 2004 Jan;15(1):123-8. link to original article PubMed
    1. Update: Proctor SJ, Wilkinson J, Jones G, Watson GC, Lucraft HH, Mainou-Fowler T, Culligan D, Galloway MJ, Wood KM, McNally RJ, James PW, Goodlad JR. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood. 2012 Jun 21;119(25):6005-15. Epub 2012 May 10. link to original article PubMed
  2. Zallio F, Tamiazzo S, Monagheddu C, Merli F, Ilariucci F, Stelitano C, Liberati AM, Mannina D, Vitolo U, Angelucci E, Rota Scalabrini D, Vallisa D, Bellei M, Bari A, Ciccone G, Salvi F, Levis A. Reduced intensity VEPEMB regimen compared with standard ABVD in elderly Hodgkin lymphoma patients: results from a randomized trial on behalf of the Fondazione Italiana Linfomi (FIL). Br J Haematol. 2016 Mar;172(6):879-88. Epub 2016 Jan 13. link to original article PubMed

Relapsed/refractory

BEACOPP, escalated dose

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen #1

Study Evidence
Johnson et al. 2016 (RATHL) Non-randomized

Treatment preceded by ABVD x 2, with interim PET-CT showing Deauville score 4 or 5 refractory disease.

Chemotherapy

Supportive medications

3-week cycle for 3 to 4 cycles

Regimen #2

Study Evidence
Press et al. 2016 (SWOG S0816) Phase II

Treatment preceded by ABVD x 2, with interim PET-CT showing Deauville score 4 or 5 refractory disease.

Chemotherapy

3-week cycle for 6 cycles

References

  1. Press OW, Li H, Schöder H, Straus DJ, Moskowitz CH, LeBlanc M, Rimsza LM, Bartlett NL, Evens AM, Mittra ES, LaCasce AS, Sweetenham JW, Barr PM, Fanale MA, Knopp MV, Noy A, Hsi ED, Cook JR, Lechowicz MJ, Gascoyne RD, Leonard JP, Kahl BS, Cheson BD, Fisher RI, Friedberg JW. US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816. J Clin Oncol. 2016 Jun 10;34(17):2020-7. Epub 2016 Apr 11. link to original article refers to original protocol link to PMC article PubMed
  2. Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed

BEACOPP-14

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BEACOPP-14: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone, 14-day course

Regimen

Study Evidence
Johnson et al. 2016 (RATHL) Non-randomized

Treatment preceded by ABVD x 2, with interim PET-CT showing Deauville score 4 or 5 refractory disease.

Chemotherapy

Supportive medications

2-week cycle for 4 to 6 cycles

References

  1. Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed

BeGEV

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BeGEV: Bendamustine, GEmcitabine, Vinorelbine

Regimen

Study Evidence
Santoro et al. 2016 Phase II

Chemotherapy

Supportive medications

  • Growth factor support
  • PJP prophylaxis and antiemetics in accordance with institutional guidelines

21-day cycle for 4 cycles

Patients in who achieved a CR or PR proceeded to BEAM -> autologous hematopoietic cell transplant or FEAM -> autologous hematopoietic cell transplant.

References

  1. Santoro A, Mazza R, Pulsoni A, Re A, Bonfichi M, Zilioli VR, Salvi F, Merli F, Anastasia A, Luminari S, Annechini G, Gotti M, Peli A, Liberati AM, Di Renzo N, Castagna L, Giordano L, Carlo-Stella C. Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. J Clin Oncol. 2016 Sep 20;34(27):3293-9. Epub 2016 Jul 5. link to original article contains verified protocol PubMed

Bendamustine

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Regimen

Study Evidence
Moskowitz et al. 2013 Phase II

Chemotherapy

Note: these infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

  • Bendamustine 120 mg/m2 IV over 30 minutes once per day on days 1 & 2

Supportive medications

28-day cycle for up to 6 cycles

References

  1. Moskowitz AJ, Hamlin PA Jr, Perales MA, Gerecitano J, Horwitz SM, Matasar MJ, Noy A, Palomba ML, Portlock CS, Straus DJ, Graustein T, Zelenetz AD, Moskowitz CH. Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2013 Feb 1;31(4):456-60. Epub 2012 Dec 17. link to original article contains verified protocol link to PMC article PubMed
  2. Retrospective: Anastasia A, Carlo-Stella C, Corradini P, Salvi F, Rusconi C, Pulsoni A, Hohaus S, Pregno P, Viviani S, Brusamolino E, Luminari S, Giordano L, Santoro A. Bendamustine for Hodgkin lymphoma patients failing autologous or autologous and allogeneic stem cell transplantation: a retrospective study of the Fondazione Italiana Linfomi. Br J Haematol. 2014 Jul;166(1):140-2. Epub 2014 Mar 7. link to original article PubMed

Bendamustine & Brentuximab vedotin

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Regimen

Study Evidence
LaCasce et al. 2014 Phase II

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. Abstract: LaCasce A, Bociek RG, Matous J, et al. Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy. Presented at: 2014 ASH Annual Meeting; December 6-9, 2014; San Francisco, CA. Abstract 293 link to abstract.

Brentuximab vedotin (Adcetris)

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Regimen #1

Study Evidence
Younes et al. 2012 (SG035-0003) Phase II
Gopal et al. 2012 Non-randomized
Bartlett et al. 2014 Phase II

Note: Bartlett et al. 2014 is a re-treatment trial; all patients were previously exposed to brentuximab vedotin. Patients who had received the 1.2 mg/kg dose on a prior trial also received that dose at re-treatment.

Chemotherapy

Supportive medications

  • Rothe et al. 2012: "no premedications were administered"

21-day cycles, given until progression or up to 16 infusions (SG035-0003)

Regimen #2

Study Evidence
Moskowitz et al. 2015 Phase II

Chemotherapy

28-day cycle for 2 cycles

PET-negative patients (a Deauville score of 1 or 2) proceeded to autologous hematopoietic cell transplant with BEAM, CBV, or high dose chemoradiotherapy. All others proceeded to receive two cycles of augmented ICE prior to transplant.

References

  1. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. Epub 2012 Mar 26. link to original article contains verified protocol link to PMC article PubMed
    1. Update: Gopal AK, Chen R, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Chi X, Sievers EL, Younes A. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015 Feb 19;125(8):1236-43. Epub 2014 Dec 22. link to original article link to PMC article PubMed
    2. Update: Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, Fong A, Younes A. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016 Sep 22;128(12):1562-6. Epub 2016 Jul 18. link to original article link to PMC article PubMed
  2. Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. link to original article contains verified protocol link to PMC article PubMed
  3. Retrospective: Rothe A, Sasse S, Goergen H, Eichenauer DA, Lohri A, Jäger U, Bangard C, Böll B, von Bergwelt Baildon M, Theurich S, Borchmann P, Engert A. Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012 Aug 16;120(7):1470-2. Epub 2012 Jul 11. link to original article contains verified protocol PubMed
  4. Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. link to original article contains verified protocol link to PMC article PubMed
  5. Retrospective: Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. Epub 2014 Feb 24. link to original article PubMed
  6. Bartlett NL, Chen R, Fanale MA, Brice P, Gopal A, Smith SE, Advani R, Matous JV, Ramchandren R, Rosenblatt JD, Huebner D, Levine P, Grove L, Forero-Torres A. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol. 2014 Mar 19;7:24. link to original article contains verified protocol link to PMC article PubMed
  7. Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J, Grewal R, Hamlin PA, Horwitz S, Kobos R, Kumar A, Matasar M, Noy A, Palomba ML, Perales MA, Portlock CS, Sauter C, Shukla N, Steinherz P, Straus D, Trippett T, Younes A, Zelenetz A, Moskowitz CH. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol. 2015 Mar;16(3):284-92. Epub 2015 Feb 13. link to original article contains protocol PubMed
  8. Chen R, Palmer JM, Martin P, Tsai N, Kim Y, Chen BT, Popplewell L, Siddiqi T, Thomas SH, Mott M, Sahebi F, Armenian S, Leonard J, Nademanee A, Forman SJ. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2015 Dec;21(12):2136-40. Epub 2015 Jul 26. link to original article link to PMC article PubMed

DHAP

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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Valesquez et al. 1988 Phase II
Sureda et al. 2011 Phase II

Chemotherapy

  • Dexamethasone 40 mg PO/IV over 15 minutes once per day on days 1 to 4
  • Cytarabine (Cytosar) as follows:
    • 70 and younger: 2000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
    • >70 years old: 1000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1

Supportive medications

  • Normal saline with mannitol 50 g/L given at 250 mL/H x 36 hours, starting 6 hours before Cisplatin (Platinol) infusion was started

21 to 28-day cycles (depending on degree of myelosuppression)

Velasquez et al. 1988 gave 6 to 10 cycles, with therapy given 4 cycles beyond the maximum antitumor effect. Sureda et al. 2011 gave 2 cycles, with responders proceeding to RIC allogeneic hematopoietic cell transplant.

  • Aside from the table below (from Velasquez et al. 1988), there were no specific cutoff criteria about dose modifications or delays of treatment.
Dose modifications
Event Cytarabine (Cytosar) Cisplatin (Platinol)
ANC less than 200/uL 1000 mg/m2 x 2 doses 100 mg/m2
Platelets less than 20 x 109/L 1000 mg/m2 x 2 doses 100 mg/m2
Sepsis associated with neutropenia 500 mg/m2 x 1 dose 100 mg/m2
Cr 1.5 to 2.0 - 75 mg/m2
Cr 2.1-3.0 - 50 mg/m2

References

  1. Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains protocol PubMed
  2. Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains protocol link to PMC article PubMed

DHAP - time intensified

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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Josting et al. 2002 Phase II

This was used as a salvage regimen for relapsed/refractory Hodgkin Lymphoma in patients who were planned for high-dose chemotherapy (HDCT) and autologous hematopoietic cell transplantation.

Chemotherapy

Supportive medications

Variable number of days between cycles depending on count recovery x 2 cycles Median time between cycle 1 and 2 was 16 days. The paper did not definitively specify what criteria needed to be fulfilled before cycle 2 was given. Baseline eligibility criteria for the study included WBC count greater than 3.5 x 109/L, Hb greater than or equal to 8 g/dL, platelets greater than or equal to 100 x 109/L.

References

  1. Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH, Dörken B, Hossfeld DK, Diehl V, Engert A; Participating Centers. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol. 2002 Oct;13(10):1628-35. link to original article contains protocol PubMed

ESHAP

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ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Aparicio et al. 1999 Phase II

Note that the authors state that they used the protocol defined by Velasquez et al. 1994. However, there are some differences in the text describing methylprednisolone dosing from that in the original article. Below are the doses reported in the original article, with the addition of G-CSF as specified in Aparicio et al. 1999.

Chemotherapy

Supportive medications

21- to 28-day cycle for 3 cycles; see below

Transplant eligible patients with "responsive disease" after 3 cycles proceeded to receive CBV followed by autologous transplant. Transplant ineligible patients with "responsive disease" received 3 more cycles of ESHAP (6 total).

References

  1. Aparicio J, Segura A, Garcerá S, Oltra A, Santaballa A, Yuste A, Pastor M. ESHAP is an active regimen for relapsing Hodgkin's disease. Ann Oncol. 1999 May;10(5):593-5. link to original article contains verified protocol PubMed

Everolimus (Afinitor)

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Regimen

Study Evidence
Johnston et al. 2010 Phase II

Chemotherapy

Supportive medications

  • "Patients could receive white blood cell growth factors if neutropenia developed. Erythropoietin treatment for anemia was permitted."

28-day cycles, given until progression or unacceptable toxicity

References

  1. Johnston PB, Inwards DJ, Colgan JP, Laplant BR, Kabat BF, Habermann TM, Micallef IN, Porrata LF, Ansell SM, Reeder CB, Roy V, Witzig TE. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010 May;85(5):320-4. link to original article contains verified protocol link to PMC article PubMed

GCD +/- R

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GCD +/- R: Gemcitabine, Carboplatin, Dexamethasone, Rituximab

Regimen

Study Evidence
Gopal et al. 2010 Phase II

Chemotherapy

Supportive medications

  • Growth factor support and antibiotic prophylaxis used is at the discretion of the treating physician.

3-week cycle for up to 4 cycles

Dose modifications

  • Gemcitabine (Gemzar):
    • If on day 8, platelets are 50 to 100 x 109/L or ANC 500 to 1000/uL: reduce dose by 25% for that dose only.
    • If on day 8, platelets are less than 50 x 109/L or ANC less than 500/uL: No day 8 dose given.
    • Subsequent cycles would be given at full dose if patients had platelets greater than or equal to 50 x 109/L or ANC greater than or equal to 1000/uL.
    • If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.

References

  1. Gopal AK, Press OW, Shustov AR, Petersdorf SH, Gooley TA, Daniels JT, Garrison MA, Gjerset GF, Lonergan M, Murphy AE, Smith JC, Pagel JM. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010 Aug;51(8):1523-9. contains protocol link to PMC article PubMed

Gemcitabine (Gemzar)

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Regimen

Study Evidence
Santoro et al. 2000 Phase II

Chemotherapy

  • Gemcitabine (Gemzar) as follows:
    • Cycle 1: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
    • Subsequent cycles (if no hematologic or nonhematologic toxicities): 1500 mg/m2 IV over 30 minutes once per day on days 1, 8, 15

4-week cycles until progression or intolerance

References

  1. Santoro A, Bredenfeld H, Devizzi L, Tesch H, Bonfante V, Viviani S, Fiedler F, Parra HS, Benoehr C, Pacini M, Bonadonna G, Diehl V. Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. J Clin Oncol. 2000 Jul;18(13):2615-9. link to original article contains verified protocol PubMed

Gemcitabine & Rituximab

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Regimen

Study Evidence
Oki et al. 2007 Phase II

Patients had received at least 2 prior chemotherapy regimens.

Chemotherapy

21-day cycle for up to 6 cycles

Dose modifications

  • Gemcitabine (Gemzar):
    • Dose level 0: 1250 mg/m2
    • Dose level -1: 1000 mg/m2
    • Dose level -2: 750 mg/m2
    • If ANC less than or equal to 1000/uL on day 1 of the following cycle, delay until count recovery
    • If ANC remains less than or equal to 1000/uL for one week or longer, reduce dose by one level
    • If platelets less than or equal to 50 x 109/L on day 1 of the following cycle, delay until count recovery AND reduce dose by one level

References

  1. Oki Y, Pro B, Fayad LE, Romaguera J, Samaniego F, Hagemeister F, Neelapu S, McLaughlin P, Goy A, Younes A. Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma. Cancer. 2008 Feb 15;112(4):831-6. link to original article contains verified protocol PubMed

GVD

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GVD: Gemcitabine, Vinorelbine, Doxil (Liposomal doxorubicin)

Regimen

Study Evidence
Bartlett et al. 2007 (CALGB 59804) Phase II

Transplant-naive patients

3-week cycle for 2 to 6 cycles

Post-transplant patients

3-week cycle for 2 to 6 cycles

Dose levels: Note: These dose levels are listed primarily for historical purposes and were used in the trial while dose levels and dose limiting toxicities (DLT) and maximum tolerated dose (MTD) were being determined. The MTD dosages used above correspond to dose level 1 for transplant-naive patients and dose level -1 for post-transplant patients.

Dose modifications

  • Gemcitabine (Gemzar):
    • If on day 8, platelets are 50 to 100 x 109/L or ANC 500 to 1000/uL: reduce dose by 25% for that dose only.
    • If on day 8, platelets are less than 50 x 109/L or ANC less than 500/uL: No day 8 dose given.
    • Subsequent cycles would be given at full dose if patients had platelets greater than or equal to 50 x 109/L or ANC greater than or equal to 1000/uL.
    • If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.

References

  1. Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K, Zelenetz AD, Cheson BD, Canellos GP; Cancer Leukemia Group B. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007 Jun;18(6):1071-9. link to original article contains protocol PubMed

GVP

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GVP: Gemcitabine, Vinorelbine, Prednisolone

Regimen

Study Evidence
Naqi et al. 2013 Phase II

Chemotherapy

28-day cycle for 4 cycles

References

  1. Naqi N, Ahmad S, Shah I, Khattak J. A multicentre phase-II feasibility study evaluating gemcitabine/vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma. J Coll Physicians Surg Pak. 2013 Jun;23(6):397-400. PubMed

ICE

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ICE: Ifosfamide, Carboplatin, Etoposide

Regimen #1

Study Evidence
Moskowitz et al. 2001 Phase II

Chemotherapy

Supportive medications

  • Mesna (Mesnex) 5000 mg/m2 IV continuous infusion over 24 hours on day 2; mixed in same solution as Ifosfamide (Ifex)
  • Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12
  • No dose reductions--treatment is delayed until ANC is greater than 1000/uL and platelets greater than 50 x 109/L

2-week cycle for 2 cycles

Regimen #2, "Augmented ICE"

Study Evidence
Moskowitz et al. 2015 Phase II

Treatment preceded by brentuximab vedotin.

Chemotherapy

Supportive medications

2 cycles

Autologous hematopoietic cell transplant was "considered" after 2 cycles; criteria not listed in the abstract.

References

  1. Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O'Brien JP, Straus D, Portlock CS, Yahalom J. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001 Feb 1;97(3):616-23. link to original article contains protocol PubMed
  2. Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J, Grewal R, Hamlin PA, Horwitz S, Kobos R, Kumar A, Matasar M, Noy A, Palomba ML, Perales MA, Portlock CS, Sauter C, Shukla N, Steinherz P, Straus D, Trippett T, Younes A, Zelenetz A, Moskowitz CH. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol. 2015 Mar;16(3):284-92. Epub 2015 Feb 13. link to original article contains protocol PubMed

Ifosfamide & Vinorelbine

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Regimen

Study Evidence
Bonfante et al. 1998 Phase II

Chemotherapy

Supportive medications

3-week cycles

References

  1. Bonfante V, Viviani S, Santoro A, Devizzi L, Di Russo A, Zanini M, Soncini F, Soto Parra H, Valagussa P, Bonadonna G. Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease. Br J Haematol. 1998 Nov;103(2):533-5. link to original article contains verified protocol PubMed
  2. Bonfante V, Viviani S, Devizzi L, Di Russo A, Di Nicola M, Magni M, Matteucci P, Grisanti S, Valagussa P, Bonadonna G, Gianni AM. High-dose ifosfamide and vinorelbine as salvage therapy for relapsed or refractory Hodgkin's disease. Eur J Haematol Suppl. 2001 Jul;64:51-5. contains protocol PubMed

IGEV

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IGEV: Ifosfamide, GEmcitabine, Vinorelbine

Regimen

Study Evidence
Santoro et al. 2007 Phase II
Zinzani et al. 2016 (HD0801) Non-randomized

Treatment in HD0801 was preceded by ABVD x 2.

Chemotherapy

Supportive medications

  • 2L saline solution hyperhydration days 1 to 4
  • Mesna (Mesnex) 2600 mg/m2 IV once per day on days 1 to 4
  • Filgrastim (Neupogen) (dose not specified, but could assume 5 mcg/kg) SC once per day on days 7 to 12, or up to apheresis in the course of hematopoietic cell mobilization

21-day cycle for 4 cycles

Patients in HD0801 who achieved a CR proceeded to BEAM -> autologous hematopoietic cell transplant.

References

  1. Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M, Nozza A, Sarina B, Morenghi E, Castagna L, Tirelli U, Balzarotti M. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica. 2007 Jan;92(1):35-41. link to original article contains verified protocol PubMed
  2. Zinzani PL, Broccoli A, Gioia DM, Castagnoli A, Ciccone G, Evangelista A, Santoro A, Ricardi U, Bonfichi M, Brusamolino E, Rossi G, Anastasia A, Zaja F, Vitolo U, Pavone V, Pulsoni A, Rigacci L, Gaidano G, Stelitano C, Salvi F, Rusconi C, Tani M, Freilone R, Pregno P, Borsatti E, Sacchetti GM, Argnani L, Levis A. Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study. J Clin Oncol. 2016 Apr 20;34(12):1376-85. Epub 2016 Feb 16. link to original article refers to Santoro et al. 2007 PubMed

Lenalidomide (Revlimid)

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Regimen

Study Evidence
Fehniger et al. 2011 Phase II

Chemotherapy

Supportive medications

28-day cycles

References

  1. Fehniger TA, Larson S, Trinkaus K, Siegel MJ, Cashen AF, Blum KA, Fenske TS, Hurd DD, Goy A, Schneider SE, Keppel CR, Wagner-Johnston ND, Carson KR, Bartlett NL. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood. 2011 Nov 10;118(19):5119-25. Epub 2011 Sep 21. link to original article contains verified protocol link to PMC article PubMed

MINE

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MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide

Regimen

Study Evidence
Rodriguez et al. 1995 Phase II

Chemotherapy

3 to 4-week cycle for up to 6 cycles in responding patients

References

  1. Rodriguez MA, Cabanillas FC, Hagemeister FB, McLaughlin P, Romaguera JE, Swan F, Velasquez W. A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas. Ann Oncol. 1995 Jul;6(6):609-11. link to original article contains protocol PubMed

Mini-BEAM

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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen #1

Study Evidence
Fernández-Jiménez et al. 1999 Phase II

Chemotherapy

4-week cycle for 2 to 3 cycles

Regimen #2

Study Evidence
Colwill et al. 1995 Phase II

Chemotherapy

Supportive medications

  • If febrile neutropenia occurred during previous cycle: Ciprofloxacin (Cipro) 500 mg PO once per day
  • Patients were transfused to keep Hb greater than or equal to 8 g/dL, platelets greater than or equal to 20 x 109/L
  • There was no routine use of G-CSF or GM-CSF

4 to 6 week cycles, depending on hematologic recovery

Patients eligible for autologous hematopoietic cell transplant received no more than 2 cycles; otherwise total # of cycles not reported

References

  1. Colwill R, Crump M, Couture F, Danish R, Stewart AK, Sutton DM, Scott JG, Sutcliffe SB, Brandwein JM, Keating A. Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol. 1995 Feb;13(2):396-402. link to original article contains protocol PubMed
  2. Fernández-Jiménez MC, Canales MA, Ojeda E, de Bustos JG, Aguado MJ, Hernández-Navarro F. Salvage chemotherapy with mini-BEAM for relapsed or refractory Hodgkin's disease prior to autologous peripheral blood stem cell transplantation. Haematologica. 1999 Nov;84(11):1007-11. link to original article contains verified protocol PubMed
    1. Update: Martín A, Fernández-Jiménez MC, Caballero MD, Canales MA, Pérez-Simón JA, García de Bustos J, Vázquez L, Hernández-Navarro F, San Miguel JF. Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease. Br J Haematol. 2001 Apr;113(1):161-71. link to original article contains protocol PubMed

Nivolumab (Opdivo)

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Regimen #1, every 2 weeks

Study Evidence
Younes et al. 2016 Phase II

Immunotherapy

Continued until disease progression or treatment intolerance

Regimen #2, with lead-in

Study Evidence
Ansell et al. 2014 Non-randomized

Immunotherapy

Continued until disease progression, or complete response, or up to 2 years

References

  1. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma. N Engl J Med. 2015 Jan 22;372(4):311-9. Epub 2014 Dec 6. link to original article contains verified protocol link to PMC article PubMed
  2. Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MG, Ligon AH, Engert A. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1283-94. Epub 2016 Jul 20. link to original article contains protocol PubMed

O-ESHAP

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O-ESHAP: Ofatumumab, Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Martínez et al. 2016 (GELTAMO) Phase II

Note that the ofatumumab dosing is described in the abstract but the ESHAP is not. The ESHAP doses here are from the protocol defined by Velasquez et al. 1994.

Chemotherapy

Number of cycles not specified

References

  1. Martínez C, Díaz-López A, Rodriguez-Calvillo M, García-Sanz R, Terol MJ, Pérez-Ceballos E, Jiménez MJ, Cantalapiedra A, Domingo-Domenech E, Rodriguez MJ, Sampol A, Espeso M, López FJ, Briones J, García JF, Sureda A; Hodgkin Lymphoma Subcommittee of Spanish Group of Lymphoma Bone Marrow Transplantation(GELTAMO). Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy. Br J Haematol. 2016 Sep;174(6):859-67. 2016 May 17. link to original article contains protocol PubMed

Panobinostat (Farydak)

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Regimen

Study Evidence ORR Pt Population
Younes et al. 2012 Phase II Investigator assessment: 27%
Central review: 22% 		Progressed after autoHCT and had a median of 4 prior systemic regimens (range 2 to 7)

Chemotherapy

21-day cycles until progression or intolerance

References

  1. Younes A, Sureda A, Ben-Yehuda D, Zinzani PL, Ong TC, Prince HM, Harrison SJ, Kirschbaum M, Johnston P, Gallagher J, Le Corre C, Shen A, Engert A. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2197-203. Epub 2012 Apr 30. link to original article contains verified protocol PubMed

Pembrolizumab (Keytruda)

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Regimen

Study Evidence ORR
Moskowitz al. 2016 (KEYNOTE-087) Phase II 65-68%

Immunotherapy

21-day cycles

References

  1. Abstract: Moskowitz, C. H., Zinzani, P. L., Fanale, M. A., Armand, P., Johnson, N. A., Radford, J. A., Ribrag, V., Molin, D., Vassilakopoulos, T. P., Tomita, A., von Tresckow, B., Shipp, M. A., Gustafson, E., Zhang, Y., Ricart, A. D., Balakumaran, A., & Chen, R. W. (2016). Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase 2 Keynote-087 Study. Blood, 128(22), 1107. link to abstract

Rituximab monotherapy

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Regimen

Study Evidence
Younes et al. 2003 Pilot, >20 pts

Patients had received a minimum of 2 prior systemic regimens. All reported patients had nodular sclerosis histology.

Chemotherapy

6-week course (6 doses total)

References

  1. Younes A, Romaguera J, Hagemeister F, McLaughlin P, Rodriguez MA, Fiumara P, Goy A, Jeha S, Manning JT Jr, Jones D, Abruzzo LV, Medeiros LJ. A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer. 2003 Jul 15;98(2):310-4. link to original article contains verified protocol PubMed

Sirolimus & Vorinostat

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Regimen

Study Evidence
Janku et al. 2014 Non-randomized

This is a very heavily pre-treated cohort, median of 6 prior therapies; doses here are one level below MTD and are proposed as the ongoing doses to be studied.

Chemotherapy

28-day cycles

References

  1. Abstract: Filip Janku, Yasuhiro Oki, Gerald Steven Falchook, Vivek Subbiah, Aung Naing, Vivianne Marie Velez Bravo, David S. Hong, Jason R. Westin, Cesar Nunez, Luis Fayad, Sattva Swarup Neelapu, Larry W. Kwak, Elizabeth J. Shpall, Jennifer J. Wheler, Tamara Barnes, Winnie S. Liang, Bodour Salhia, Funda Meric-Bernstam, Razelle Kurzrock, Michelle A. Fanale. Activity of the mTOR inhibitor sirolimus and HDAC inhibitor vorinostat in heavily pretreated refractory Hodgkin lymphoma patients. J Clin Oncol 32:5s, 2014 (suppl; abstr 8508) link to original abstract

Vinblastine (Velban)

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Regimen

Study Evidence
Little et al. 1998 Retrospective

This is a retrospective study; we are not aware of a prospective trial of vinblastine monotherapy in this setting.

Chemotherapy

1 to 2-week cycles

References

  1. Retrospective: Little R, Wittes RE, Longo DL, Wilson WH. Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. J Clin Oncol. 1998 Feb;16(2):584-8. link to original article PubMed

Vinorelbine (Navelbine)

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Regimen

Study Evidence
Devizzi et al. 1994 Phase II

Chemotherapy

Complete responders received 6 additional doses past CR; others continued until progression or a maximum of 24 doses

References

  1. Devizzi L, Santoro A, Bonfante V, Viviani S, Balzarini L, Valagussa P,vBonadonna G. Vinorelbine: an active drug for the management of patients withvheavily pretreated Hodgkin's disease. Ann Oncol. 1994 Nov;5(9):817-20. link to original article contains verified protocol PubMed

Consolidation and/or maintenance after salvage therapy

Allogeneic hematopoietic cell transplant

Usually reserved for patients relapsing after autologous hematopoietic cell transplant, and then for younger and very fit individuals. The regimens below have been specifically studied in the setting of relapsed/refractory Hodgkin lymphoma; for other regimens please go to the transplant conditioning regimens page.

Regimen #1

To be completed. Treatment preceded by salvage brentuximab vedotin.

Regimen #2

Study Evidence
Sureda et al. 2011 Phase II

Treatment preceded by DHAP x 2.

Preparative regimen

Recipients of hematopoietic cells from matched unrelated donors also received:

Graft-versus-host disease prophylaxis

  • Cyclosporine A (not specified whether modified or non-modified) starting on day -2 at 1.5 mg/kg IV BID
  • Methotrexate (MTX) 10 mg/m2 IV once per day on days +1, +3, +6, +11

If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +180.

Regimen #3

Study Evidence
Anderlini et al. 2008 Phase II

Patients had "chemosensitive or stable disease after salvage treatment." The regimen as reported here is what the authors were using towards the end of the study period; see paper for details.

Preparative regimen

Recipients of hematopoietic cells from matched unrelated donors also received:

Graft-versus-host disease prophylaxis

  • Tacrolimus (Prograf) IV starting on day -2, dosed to achieve serum levels 4–12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given).
  • Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients)

Regimen #4

Study Evidence
Sobol et al. 2013 Phase II

BEAM is the preparative regimen; further details not available in the abstract.

References

  1. Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. link to original article contains protocol PubMed
  2. Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, Hosing C, Khouri IF, Couriel D, de Lima M, Qazilbash MH, Pro B, Romaguera J, Fayad L, Hagemeister F, Younes A, Munsell MF, Champlin RE. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. link to original article contains verified protocol link to PMC article PubMed
  3. Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains verified protocol link to PMC article PubMed
  4. Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. link to original article PubMed
  5. Illidge T, Bouabdallah R, Chen R, Gopal AK, Moskowitz CH, Ramchandren R, Shustov AR, Tilly H, Trippett TM, Gibb A, Grove LE, Advani R. Allogeneic transplant following brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Leuk Lymphoma. 2015 Mar;56(3):703-10. Epub 2015 Jan 21 link to original article PubMed

Autologous hematopoietic cell transplant

To be completed. Usually preceded by a high-intensity salvage chemotherapy. See details about preparative regimens.

Patients in AETHERA were randomized to brentuximab vedotin maintenance versus observation.

References

  1. Morschhauser F, Brice P, Fermé C, Diviné M, Salles G, Bouabdallah R, Sebban C, Voillat L, Casasnovas O, Stamatoullas A, Bouabdallah K, André M, Jais JP, Cazals-Hatem D, Gisselbrecht C; GELA/SFGM Study Group. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol. 2008 Dec 20;26(36):5980-7. Epub 2008 Nov 17. link to original article PubMed
    1. Update: Sibon D, Morschhauser F, Resche-Rigon M, Ghez D, Dupuis J, Marçais A, Deau-Fischer B, Bouabdallah R, Sebban C, Salles G, Brice P. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group. Haematologica. 2016 Apr;101(4):474-81. Epub 2015 Dec 31. link to original article link to PMC article PubMed
  2. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article contains verified protocol PubMed

Brentuximab vedotin (Adcetris)

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Regimen

Study Evidence Comparator Efficacy
Moskowitz et al. 2015 (AETHERA) Phase III Placebo Superior PFS

Treatment begins 30 to 45 days after autologous hematopoietic cell transplant.

Chemotherapy

3-week cycle for 16 cycles

References

  1. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article contains verified protocol PubMed

Observation

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Regimen

Study Evidence Comparator Efficacy
Moskowitz et al. 2015 (AETHERA) Phase III Brentuximab vedotin Inferior PFS

No further treatment after autologous hematopoietic cell transplant.

References

  1. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article contains verified protocol PubMed

Response criteria

NCI Sponsored International Working Group Criteria (1999)

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Intended for non-Hodgkin lymphoma (NHL) but often referred to in the Hodgkin lymphoma literature.

  1. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

Juweid's criteria (2007)

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  1. Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, Wiseman GA, Kostakoglu L, Scheidhauer K, Buck A, Naumann R, Spaepen K, Hicks RJ, Weber WA, Reske SN, Schwaiger M, Schwartz LH, Zijlstra JM, Siegel BA, Cheson BD; Imaging Subcommittee of International Harmonization Project in Lymphoma. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22. link to original article PubMed

Deauville criteria (2009)

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Note: the definition of "positive" versus "negative" varies and should be confirmed within individual protocols. This is a 5-point scale.

  • 1: no residual FDG uptake above the background level
  • 2: residual FDG uptake less than or equal to the mediastinum
  • 3: residual FDG uptake greater than the mediastinum but not greater than the liver
  • 4: residual FDG uptake moderately increased compared with the liver
  • 5: residual FDG uptake markedly increased compared with the liver or new sites of disease.

References

  1. Meignan M, Gallamini A, Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma. 2009 Aug;50(8):1257-60. link to original article PubMed
  2. Barrington SF, Qian W, Somer EJ, Franceschetto A, Bagni B, Brun E, Almquist H, Loft A, Højgaard L, Federico M, Gallamini A, Smith P, Johnson P, Radford J, O'Doherty MJ. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2010 Oct;37(10):1824-33. Epub 2010 May 27. link to original article PubMed
  3. Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, Meignan M, Malkowski B, Hofman MS, Barrington SF. International validation study for interim PET in ABVD-treated, advanced-stage hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013 May;54(5):683-90. Epub 2013 Mar 20. link to original article PubMed

Investigational agents

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