Primary mediastinal B-cell lymphoma

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Tarsheen Sethi, MD, MSCI
Yale University
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11 regimens on this page
11 variants on this page


Note: these regimens have been studied specifically in primary mediastinal B-cell lymphoma. Other large B-cell lymphoma regimens, such as those used in diffuse large B-cell lymphoma are also often used.

Guidelines

BSH

ESMO

Older

NCCN

Untreated

DA-R-EPOCH

DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study Years of enrollment Evidence
Dunleavy et al. 2013 (NCI 93-C-0133) 1999-2012 Phase 2
Purroy et al. 2014 2002-2008 Phase 2, <20 pts in this subgroup

Targeted therapy

Chemotherapy

  • Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
  • Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2; dose was not capped)
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 2 hours once on day 5
  • Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)

Glucocorticoid therapy

Supportive medications

  • Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5,000/uL past nadir
  • Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
    • Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
  • Omeprazole (Prilosec) 20 mg (or equivalent) PO once per day
  • Docusate (Colace) (dose not specified) and Sennosides (Senna) 2 tablets PO twice per day as needed for constipation
  • Lactulose 20 g PO every 6 hours as needed for constipation
  • Hepatitis B surface antigen positive patients received daily antiviral therapy until 8 weeks after completion of chemotherapy

21-day cycle for 6 to 8 cycles

Dose adjustments

  • Start cycle 1 as described above.
  • Obtain CBCs twice per week for nadir measurements.
  • If nadir ANC greater than 500, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
  • If nadir ANC less than 500, use same doses as last cycle.
  • If nadir platelet count less than 25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.

References

  1. NCI 93-C-0133: Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. link to original article link to supplementary appendix link to PMC article contains dosing details in manuscript PubMed NCT00001337
  2. Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. link to original article PubMed EudraCT 2004-001684-22

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21
CHOP-R

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) 2000-2003 Phase 3 (E-esc) 1. CHOP
2. CHOEP
3. MACOP-B
4. PMitCEBO
Seems to have superior EFS

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive medications

21-day cycle for 6 cycles

Subsequent treatment

References

  1. NCIC-CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed
    1. Subgroup analysis: Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. link to original article PubMed

R-CHOP (Prednisolone)

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21) 2005-2008 Phase 3 (C) R-CHOP-14 Might have inferior OS1

1Reported efficacy is based on a post-hoc subgroup analysis.

Targeted therapy

Chemotherapy

Glucocorticoid therapy

CNS prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

  • Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive medications

21-day cycle for 8 cycles

References

  1. UK NCRI R-CHOP14v21: Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains dosing details in manuscript PubMed ISRCTN16017947
    1. Subgroup analysis: Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. link to original article PubMed

R-CHOP-14 (Prednisolone)

R-CHOP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone every 14 days

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21) 2005-2008 Phase 3 (E-esc) R-CHOP-21 Might have superior OS1

1Reported efficacy is based on the 2016 subgroup analysis.

Targeted therapy

Chemotherapy

Glucocorticoid therapy

CNS prophylaxis

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

  • Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.

Supportive medications

14-day cycle for 6 cycles (8 cycles of rituximab)

References

  1. UK NCRI R-CHOP14v21: Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains dosing details in manuscript PubMed ISRCTN16017947
    1. Subgroup analysis: Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. link to original article PubMed

Consolidation after upfront therapy

Radiation therapy

Regimen

Study Evidence
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) Non-randomized portion of RCT

Preceding treatment

Radiotherapy

  • External beam radiotherapy: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion

References

  1. NCIC-CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains dosing details in manuscript PubMed NCT00064116
    1. Subgroup analysis: Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. link to original article PubMed

Relapsed or refractory, salvage therapy

R-DHAP

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

Regimen

Study Evidence Comparator
Crump et al. 2014 (NCIC-CTG LY.12) Phase 3, <20 pts in subgroup (C) R-GDP

Targeted therapy

Glucocorticoid therapy

Chemotherapy

  • Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1

21-day cycle for up to 3 cycles

References

  1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949

R-GDP

R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Evidence Comparator
Crump et al. 2014 (NCIC-CTG LY.12) Phase 3, <20 pts in subgroup (E-switch-ic) R-DHAP

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for up to 3 cycles

References

  1. NCIC-CTG LY.12: Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains dosing details in manuscript PubMed NCT00078949

Consolidation after salvage therapy

FluBuCy, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen

Study Evidence
Glass et al. 2014 (DSHNHL R3) Phase 2

Chemotherapy

Immunosuppressive therapy

GVHD prophylaxis

Immunotherapy

Stem cells transfused on day 0

References

  1. DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330

Relapsed or refractory, further lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Efficacy
Locke et al. 2017 (ZUMA-1) 2015-2016 Phase 1/2, <20 pts in subgroup (RT) ORR: 82%

Preceding treatment

  • Lymphodepletion with FC

Immunotherapy

Supportive medications

One course; patients with initial response and disease progression at least 3 months later could be retreated

References

  1. ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article PubMed NCT02348216
    1. Update: Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
    2. Update: Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed

Lisocabtagene maraleucel monotherapy

Regimen

Study Years of enrollment Evidence
Abramson et al. 2020 (TRANSCEND NHL-001) 2016-2019 Phase 1 (RT)

Immunotherapy

References

  1. TRANSCEND NHL-001: Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. link to original article PubMed NCT02631044

Pembrolizumab monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence
Armand et al. 2016 (KEYNOTE-013) 2014-2016 Phase 1b
Armand et al. 2016 (KEYNOTE-170) 2016-2017 Phase 2 (RT)

Immunotherapy

21-day cycle for up to 35 cycles (2 years)

References

  1. KEYNOTE-013: Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01953692
  2. KEYNOTE-170: Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02576990