Difference between revisions of "Follicular lymphoma"

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m (→‎Obinutuzumab (GA101): updated reference)
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''Note: Dose here is that recommended by the publication as having "encouraging activity with an acceptable safety profile"''
 
''Note: Dose here is that recommended by the publication as having "encouraging activity with an acceptable safety profile"''
  
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*[[Obinutuzumab (GA101)]] 1600 mg IV once on days 1 & 7 of cycle 1; then 800 mg IV once on day 1 of subsequent cycles
+
*[[Obinutuzumab (GA101)]] 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 7 of cycle 1; then, during cycles 2 to 8, [[Obinutuzumab (GA101)]] 800 mg IV once on day 1
 +
**Initial infusion rate is 50 mg/hour.  In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.
  
 
'''21-day cycles x 8 cycles'''
 
'''21-day cycles x 8 cycles'''
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===References===
 
===References===
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# Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study. J Clin Oncol. 2013 Jul 8. [Epub ahead of print] [http://jco.ascopubs.org/content/31/23/2920.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835715 PubMed]
+
# Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. doi: 10.1200/JCO.2012.46.9718. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2920.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835715 PubMed]
  
 
==Ofatumumab (Arzerra)==
 
==Ofatumumab (Arzerra)==

Revision as of 23:26, 14 September 2013

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Untreated

BR

BR: Bendamustine, Rituximab

Regimen, Mathias et al. 2012 (StiL NHL1)

Level of Evidence: Phase III

28-day cycles x up to 6 cycles

Supportive medications:

  • "Standard antiemetic prophylaxis"
  • No prophylactic antibiotics
  • Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

References

  1. Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL). Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting abstract 3. link to abstract ASCO Post article ASCO plenary session video
  2. Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. link to abstract
  3. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; on behalf of the Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Feb 19. pii: S0140-6736(12)61763-2. doi: 10.1016/S0140-6736(12)61763-2. [Epub ahead of print] link to original article contains verified protocol PubMed

Cyclophosphamide (Cytoxan)

Regimen

Level of Evidence: Phase III

  • Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day, with dose modifications according to WBC and platelet count as listed in table 1 of Peterson, et al. 2003

References

  1. Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. link to original article contains verified protocol PubMed

CF

CF: Cyclophosphamide, Fludarabine

Regimen

Level of Evidence: Phase III

28-day cycles, number not specified (regimen was notable for excess mortality)

References

  1. Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. doi: 10.1200/JCO.2008.17.1561. Epub 2009 Mar 2. link to original article contains verified protocol PubMed

CHOP

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen #1, Hiddemann et al. 2005

Level of Evidence: Phase III

21-day cycles x 6 to 8 cycles

Regimen #2, Zinzani et al. 2004

Level of Evidence: Phase III

21-day cycles x 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:

References

  1. Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. link to original article contains verified protocol PubMed
  2. Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. link to original article contains verified protocol PubMed
  3. Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. link to original article contains verified protocol PubMed

CHOP-B

CHOP-B: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone, Bleomycin

Regimen

Level of Evidence: Phase III

References

  1. Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. link to original article contains verified protocol PubMed

CHOP -> 131Iodine-Tositumomab (Bexxar)

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
CHOP-RIT: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone RadioImmunoTherapy

Regimen, Press, et al. 2003 (SWOG S9911) & Press, et al. 2013 (SWOG S0016)

Level of Evidence: Phase III

CHOP

21-day cycles x 6 cycles

Supportive medications:

  • Allopurinol (Aloprim) 300 mg PO once per day for patients with bulky disease

Tositumomab & I-131 (Bexxar) dosimetric step

  • On Day 1, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
  • Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
  • Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

Tositumomab & I-131 (Bexxar) therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
  • Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
  • Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

References

  1. Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, Gaynor ER, Rivkin SE, Fisher RI. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003 Sep 1;102(5):1606-12. Epub 2003 May 8. link to original article contains verified protocol PubMed
  2. Update: Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; Southwest Oncology Group. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. link to original article PubMed
  3. Press OW, Unger JM, Rimsza LM, Friedberg JW, Leblanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III Randomized Intergroup Trial of CHOP Plus Rituximab Compared With CHOP Chemotherapy Plus 131Iodine-Tositumomab for Previously Untreated Follicular Non-Hodgkin Lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. doi: 10.1200/JCO.2012.42.4101. Epub 2012 Dec 10. link to original article contains partial protocol PubMed

CVP

CVP: Cyclophosphamide, Vincristine, Prednisone

Synonyms: COP, COP protocol 2, VCP

Structured Concept: C9573 (NCI-T), C0056633 (NCI-MT/UMLS)

Regimen #1, Marcus, et al. 2005

Level of Evidence: Phase III

21-day cycles x up to 8 cycles

Regimen #2, Hochster, et al. 2009 (ECOG1496)

Level of Evidence: Phase III

21-day cycles x 6 to 8 cycles

Patients were then randomized to maintenance rituximab or observation.

References

  1. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article contains protocol PubMed
  2. Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. doi: 10.1200/JCO.2008.17.1561. Epub 2009 Mar 2. link to original article contains verified protocol PubMed

CVP -> 131Iodine-Tositumomab (Bexxar)

CVP: Cyclophosphamide, Vincristine, Prednisone

Regimen

Level of Evidence: Phase II

CVP

21-day cycles x 6 cycles, followed within 56 days by:

Tositumomab & I-131 (Bexxar) dosimetric step

  • On Day 1, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
  • Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
  • Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

Tositumomab & I-131 (Bexxar) therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
  • Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
  • Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO once per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion

References

  1. Link BK, Martin P, Kaminski MS, Goldsmith SJ, Coleman M, Leonard JP. Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study. J Clin Oncol. 2010 Jun 20;28(18):3035-41. doi: 10.1200/JCO.2009.27.8325. Epub 2010 May 10. link to original article PubMed .

Fludarabine -> 131Iodine-Tositumomab (Bexxar)

Regimen

Level of Evidence: Phase II

5-week cycles x 3 cycles, followed by:

Dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

  1. Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005 Aug 20;23(24):5696-704. link to original article contains verified protocol PubMed

Fludarabine & Rituximab

Regimen

Level of Evidence: Phase II

Cycle 1 begins 72 hours after the second dose of rituximab

28-day cycles x 7 cycles

References

  1. Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. link to original article contains protocol PubMed

FLUMIZ

FLUMIZ: FLUdarabine, MItoxantrone, Zevalin

Level of Evidence: Phase II

Regimen

28-day cycles x 6 cycles

Supportive medications:

  • Allopurinol (Aloprim) 300 mg PO once per day for patients with bulky disease
  • No prophylactic use of G-CSF, but patients with grade 3 or 4 neutropenia or delayed neutropenic fever could be given growth factors for later cycles at physician discretion

Patients were restaged 4-6 weeks after finishing cycle 6. People with at least a partial response (PR), neutrophil count >1.5 x 109/L, platelet count >100 x 109/L, and less than 25% bone marrow involvement were eligible for consolidation therapy with Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 6 to 10 weeks after the end of cycle 6.

Consolidation therapy

References

  1. Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. doi: 10.1016/S1470-2045(08)70039-1. Epub 2008 Mar 14. link to original article contains verified protocol PubMed

FM

FM: Fludarabine, Mitoxantrone

Regimen

Level of Evidence: Phase III

21-day cycles x 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:

References

  1. Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. link to original article contains verified protocol PubMed

FMR

FMR: Fludarabine, Mitoxantrone, Rituximab

Regimen

Level of Evidence: Phase III

21-day cycles x 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:

References

  1. Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. link to original article contains verified protocol PubMed

FMR-Z

FMR-Z: Fludarabine, Mitoxantrone, Rituximab, Zevalin

Regimen

Level of Evidence: Phase II

28-day cycles x 4 cycles

Supportive medications:

  • No prophylactic use of G-CSF, but patients with grade 3 or 4 neutropenia or delayed neutropenic fever could be given growth factors for later cycles at physician discretion

Patients were restaged 2 to 3 weeks after finishing cycle 4. People with at least a partial response (PR), neutrophil count >1.5 x 109/L, platelet count >100 x 109/L, and less than 25% bone marrow involvement were eligible for consolidation therapy with Ibritumomab tiuxetan & Yttrium-90 (Zevalin) given within 12 weeks (paper does not specify "within 12 weeks" of what).

Consolidation therapy

References

  1. Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by ⁹⁰Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. doi: 10.1093/annonc/mdr145. Epub 2011 May 2. link to original article contains verified protocol PubMed

131Iodine-Tositumomab (Bexxar)

Regimen

Level of Evidence: Phase II

Dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

  1. Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9. link to original article contains verified protocol PubMed

MCP

MCP: Mitoxantrone, Chlorambucil, Prednisolone

Regimen

Level of Evidence: Phase III

28-day cycles x up to 8 cycles

References

  1. Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. link to original article contains verified protocol PubMed

O-CHOP

O-CHOP: Ofatumumab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Level of Evidence: Phase II

Regimen, Czuczman, et al. 2012 (409 Study)

21-day cycles x 6 cycles

Supportive medications:

  • Acetaminophen (Tylenol) 1000 mg (no route specified) before each dose of ofatumumab
  • Cetirizine (Zyrtec) 10 mg (or equivalent) PO before each dose of ofatumumab
  • Prednisolone (Millipred) (or equivalent) 100 mg before dose 1 and 2 of ofatumumab

References

  1. Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Strange C, Windfeld K, Viardot A; 409 Study Investigators. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012 May;157(4):438-45. doi: 10.1111/j.1365-2141.2012.09086.x. Epub 2012 Mar 13. link to original article contains verified protocol PubMed

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen #1, Hiddemann, et al. 2005

Level of Evidence: Phase III Improved OS Increased toxicity

21-day cycles x 6 to 8 cycles

Regimen #2, Czuczman, et al. 1999 & Press, et al. 2013 (SWOG S0016)

Level of Evidence: Phase III

21-day cycles x 6 cycles

Regimen #3, Watanabe, et al. 2011 (JCOG 0203)

Level of Evidence: Phase III

21-day cycles x 6 cycles

Supportive medications:

Regimen #4, Federico, et al. 2013 (FOLL05)

Level of Evidence: Phase III

21-day cycles x 6 cycles, with two additional cycles of rituximab alone

Regimen #5, Zinzani et al. 2004

Level of Evidence: Phase III

21-day cycles x 6 cycles; patients with PR or CR with detectable bcl-2/IgH fusion by PCR received:

References

  1. Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. link to original article contains protocol PubMed
  2. Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. link to original article contains verified protocol PubMed
  3. Update: Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. link to original article PubMed
  4. Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. link to original article contains protocol PubMed
  5. Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Takeuchi K, Nawano S, Terauchi T, Hotta T. Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol. 2011 Oct 20;29(30):3990-8. doi:10.1200/JCO.2011.34.8508. Epub 2011 Sep 19. link to original article contains verified protocol PubMed
  6. Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. link to abstract
  7. Press OW, Unger JM, Rimsza LM, Friedberg JW, Leblanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III Randomized Intergroup Trial of CHOP Plus Rituximab Compared With CHOP Chemotherapy Plus 131Iodine-Tositumomab for Previously Untreated Follicular Non-Hodgkin Lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. doi: 10.1200/JCO.2012.42.4101. Epub 2012 Dec 10. link to original article PubMed
  8. Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Follicular Lymphoma: Results of the FOLL05 Trial Conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Mar 25. [Epub ahead of print] link to original article contains verified protocol PubMed

R-CHOP -> 90Yttrium-Ibritumomab-Tiuxetan (Zevalin)

Regimen #1, Hainsworth et al. 2009

Level of Evidence: Phase II

Four week course, followed by:

21-day cycles x 3 cycles, followed in 4 weeks by:

See text for further information about Zevalin eligbility criteria. If patient did not meet criteria within 7 weeks after final R-CHOP, Zevalin was omitted.

Regimen #2, Jacobs et al. 2008

Level of Evidence: Phase II

R-CHOP given as per standard ECOG dosing, except that rituximab is given on day 1 of each cycle:

Supportive medications:

21-day cycles x 3 cycles, followed by Zevalin:

Interval between R-CHOP and Zevalin is not specified in the paper

8-day course of therapy, followed in 1 to 2 weeks by:

Four week course

References

  1. Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. doi: 10.1158/1078-0432.CCR-08-0529. link to original article contains verified protocol PubMed
  2. Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by Yttrium-90 Ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. doi: 10.3816/CLM.2009.n.044. link to original article contains verified protocol PubMed

R-CHVP+I

R-CHVP+I: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, VP-16 (etoposide), Prednisolone, Interferon-α2a

Regimen

Level of Evidence: Phase III

28-day cycles x 6 cycles, then

Continuously for 18 months

References

  1. Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. doi: 10.1182/blood-2008-04-153189. Epub 2008 Sep 17. link to original article contains verified protocol PubMed

R-CVP

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Level of Evidence: Phase III Improved OS Similar toxicity

Regimen

21-day cycles x up to 8 cycles

References

  1. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article contains protocol PubMed
  2. Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. link to original article PubMed
  3. Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. link to abstract
  4. Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Follicular Lymphoma: Results of the FOLL05 Trial Conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Mar 25. [Epub ahead of print] link to original article contains verified protocol PubMed

R-FM

R-FM: Rituximab, Fludarabine, Mitoxantrone

Regimen, Federico et al. 2013 (FOLL05)

Level of Evidence: Phase III

21-day cycles x 6 cycles, with 2 additional cycles of rituximab alone

References

  1. Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Follicular Lymphoma: Results of the FOLL05 Trial Conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Mar 25. [Epub ahead of print] link to original article contains verified protocol PubMed

R-MCP

R-MCP: Rituximab, Mitoxantrone, Chlorambucil, Prednisolone

Regimen

Level of Evidence: Phase III

28-day cycles x up to 8 cycles

References

  1. Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. link to original article contains verified protocol PubMed

Rituximab monotherapy

Regimen

Level of Evidence: Phase II

  • Rituximab (Rituxan) 375 mg/m2 IV weekly x 4 weeks; initial infusion rate of 50 mg/H, then increased as tolerated by 50 mg/H every 30 minutes, to a maximum rate of 300 mg/H

4-week course

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose of rituximab
  • Diphenhydramine (Benadryl) 50 mg PO 30 minutes prior to each dose of rituximab

Patients with response or stable disease at 12 weeks in Ghielmini et al, 2004 were randomized to maintenance rituximab or no further treatment.

References

  1. Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haïoun C, Foussard C, Sebban C, Stamatoullas A, Milpied N, Boué F, Taillan B, Lederlin P, Najman A, Thièblemont C, Montestruc F, Mathieu-Boué A, Benzohra A, Solal-Céligny P. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1;97(1):101 to 6. link to original article contains protocol PubMed
  2. Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. link to original article contains protocol PubMed
  3. Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
  4. Meta-analysis: Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. PubMed

Rituximab & Lenalidomide

Regimen

Level of Evidence: Phase II

28-day cycles up to 6 cycles

References

  1. N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036. link to abstract

90Yttrium-Ibritumomab-Tiuxetan (Zevalin)

Regimen

Level of Evidence: Phase II

Recruitment was limited to patients at least 50 years old due to radiation safety concerns

8 to 9-day course of therapy

References

  1. Scholz CW, Pinto A, Linkesch W, Lindén O, Viardot A, Keller U, Hess G, Lastoria S, Lerch K, Frigeri F, Arcamone M, Stroux A, Frericks B, Pott C, Pezzutto A. 90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial. J Clin Oncol. 2013 Jan 20;31(3):308-13. doi:10.1200/JCO.2011.41.1553. Epub 2012 Dec 10. link to original article contains verified protocol PubMed

Consolidation and/or maintenance

Observation

Regimen

Level of Evidence: Phase III

No treatment; used as a comparator arm and here for reference purposes only.

References

  1. Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. doi: 10.1200/JCO.2008.17.1561. Epub 2009 Mar 2. link to original article contains verified protocol PubMed

Rituximab monotherapy

Regimen #1, van Oers, et al. 2006 (EORTC 20981)

Level of Evidence: Phase III

3-month cycles until relapse or for a maximum of 2 years

Regimen #2, Salles, et al. 2011 (PRIMA)

Level of Evidence: Phase III

Starts 8 weeks after the last induction treatment

8-week cycles x 12 cycles

Regimen #3, Hainsworth et al. 2002

Level of Evidence: Phase II

  • Rituximab (Rituxan) 375 mg/m2 IV weekly x 4 weeks; initial infusion rate of 50 mg/H, then increased as tolerated by 50 mg/H every 30 minutes, to a maximum rate of 300 mg/H

4-week course

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose of rituximab
  • Diphenhydramine (Benadryl) 50 mg PO 30 minutes prior to each dose of rituximab

Regimen #4, Ghielmini, et al. 2004 (SAKK)

Level of Evidence: Phase III

  • Rituximab (Rituxan) 375 mg/m2 IV once at week 12, months 5, 7, 9 (8 total doses, including the initial treatment)

Total treatment course of 9 months

Regimen #5, Forstpointner, et al. 2004 (GLSG)

Level of Evidence: Phase III

Two courses at 3 and 9 months after completion of salvage therapy (8 total doses)

Regimen #6, Hochster, et al. 2009 (ECOG1496)

Level of Evidence: Phase III

Four courses, every 6 months (16 total doses)

References

  1. Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. link to original article contains protocol PubMed
  2. Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
  3. Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains verified protocol PubMed
  4. van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains verified protocol PubMed
  5. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains verified protocol PubMed
  6. Meta-analysis: Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. PubMed
  7. Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. doi: 10.1200/JCO.2008.17.1561. Epub 2009 Mar 2. link to original article contains verified protocol PubMed
  8. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains verified protocol PubMed
  9. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed

90Yttrium-Ibritumomab-Tiuxetan (Zevalin)

Regimen

Level of Evidence: Phase III

Consolidation therapy for patients in complete or partial remission after first-line therapy

8-day course of therapy

References

  1. Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. link to original article contains protocol PubMed
  2. Update: Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-Ibritumomab Tiuxetan Consolidation of First Remission in Advanced-Stage Follicular Non-Hodgkin Lymphoma: Updated Results After a Median Follow-Up of 7.3 Years From the International, Randomized, Phase III First-Line Indolent Trial. J Clin Oncol. 2013 Apr 1. [Epub ahead of print] link to original article contains protocol PubMed

Relapsed/refractory

BR

BR: Bendamustine, Rituximab

Regimen #1, Rummel, et al. 2005

Level of Evidence: Phase II

Cycle 1 is started 7 days after the first dose of rituximab

28-day cycles x 5 cycles

Regimen #2, Robinson, et al. 2008

Level of Evidence: Phase II

Cycle 1 is started 7 days after the first dose of rituximab:

28-day cycles x 4 cycles; however, the paper also said that people "could receive up to six cycles if disease regression was evident between the second and fourth cycles"

One more dose of rituximab 28 days after the fourth cycle:

References

  1. Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains protocol PubMed
  2. Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B, Cheson BD. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. link to original article contains verified protocol PubMed

BVR

BVR: Bendamustine, Velcade, Rituximab

Regimen #1, Friedberg, et al. 2011

Level of Evidence: Phase II

28-day cycles x 6 cycles

Supportive medications:

  • Premedications, antiemetic therapy, and growth factor support per institutional guidelines
  • No routine antibiotic or antiviral prophylaxis was given

Regimen #2, Fowler, et al. 2011 (VERTICAL)

Level of Evidence: Phase II

  • Bendamustine (Treanda) 50-90 mg/m2 IV over 60 minutes once on days 1 & 2, given after bortezomib and before rituximab
  • Bortezomib (Velcade) 1.6 mg/m2 IV once on days 1, 8, 15, 22, given first
  • Rituximab (Rituxan) 375 mg/m2 IV once on days 1, 8, 15, 22 of cycle 1, then 375 mg/m2 IV once on day 1 of cycles 2 to 5; given last

35-day cycles x 5 cycles

Supportive medications:

  • Antiviral prophylaxis at physician discretion

References

  1. Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. Epub 2011 Jan 14. link to original article contains protocol PubMed
  2. Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011 Sep 1;29(25):3389-95. Epub 2011 Aug 1. link to original article contains protocol PubMed

CHOP

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen, Van Oers, et al. 2006 (EORTC 20981)

Level of Evidence: Phase III

21-day cycles x 6 cycles

Responders (PR or CR) were randomized to maintenance rituximab or no further treatment.

References

  1. van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains verified protocol PubMed
  2. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains verified protocol PubMed

FCM

FCM: Fludarabine, Cyclophosphamide, Mitoxantrone

Regimen

Level of Evidence: Phase III

28-day cycles x 4 cycles

Responders (PR or CR) were randomized to maintenance rituximab or no further treatment.

References

  1. Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains verified protocol PubMed
  2. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains verified protocol PubMed

Fludarabine & Rituximab

Regimen

Level of Evidence: Phase II

Cycle 1 begins 72 hours after the second dose of rituximab

28-day cycles x 7 cycles

References

  1. Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. link to original article contains protocol PubMed

131Iodine-Tositumomab (Bexxar)

Regimen

Level of Evidence: Phase II

Dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
  • Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
  • Potassium iodide (SSKI, saturated solution of potassium iodide) 2 drops PO TID starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion; may also use Lugol’s solution or potassium iodide tablets

References

  1. Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. link to original article contains verified protocol PubMed
  2. Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. link to original article PubMed

Obinutuzumab (GA101)

Regimen, Salles, et al. 2013 (GAUGUIN)

Level of Evidence: Phase II

Note: Dose here is that recommended by the publication as having "encouraging activity with an acceptable safety profile"

  • Obinutuzumab (GA101) 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 7 of cycle 1; then, during cycles 2 to 8, Obinutuzumab (GA101) 800 mg IV once on day 1
    • Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.

21-day cycles x 8 cycles

Supportive medications:

  • Acetaminophen (no dose specified) PO 30 minutes before first infusion
  • Antihistamine (no drug or dose specified) PO 30 minutes before first infusion
  • Corticosteroids before first infusion for patients at "high risk" of infusion reaction

References

  1. Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. doi: 10.1200/JCO.2012.46.9718. Epub 2013 Jul 8. link to original article contains verified protocol PubMed

Ofatumumab (Arzerra)

Regimen, Czucman, et al. 2012 (405 Study)

Level of Evidence: Phase II

  • Ofatumumab (Arzerra) 300 mg IV once on week 1 (dose 1); then 1000 mg IV once per week thereafter (doses 2 to 8)

8-week total course

Supportive medications:

  • Acetaminophen (Tylenol) 1000 mg (no route specified) before each dose of ofatumumab
  • Cetirizine (Zyrtec) 10 mg (or equivalent) PO before each dose of ofatumumab
  • Prednisolone (Millipred) (or equivalent) 100 mg before dose 1 and 2 of ofatumumab

References

  1. Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. link to original article contains verified protocol PubMed

PEP-C

PEP-C: Prednisone, Etoposide, Procarbazine, Cyclophosphamide

Regimen

Level of Evidence: Phase II

Induction phase

Supportive medication:

  • Ondansetron (dose not specified) with each procarbazine dose

Continue until WBC <3 x 109/L, hold until WBC recovery, then titrate in maintenance phase per paper (see publication for details)

Maintenance phase

  • Same medications and doses given per day as used in the induction phase, but the number of days per week they are used is titrated to maintain a WBC of at least 3; for example, 5 out of 7 days, every other day, once per week, etc.

References

  1. Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Kaufman TP, Leonard JP. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer. 2008 May 15;112(10):2228-32. doi:10.1002/cncr.23422. link to original article contains verified protocol PubMed
  2. Coleman M, Ruan G, Elstrom RL, Martin P, Leonard JP. Metronomic therapy for refractory/relapsed lymphoma: the PEP-C low-dose oral combination chemotherapy regimen. Hematology. 2012 Apr;17 Suppl 1:S90-2. doi:10.1179/102453312X13336169155970. PubMed

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen #1, Czuczman, et al. 1999

Level of Evidence: Phase II

21-day cycles x 6 cycles

Regimen #2, Van Oers, et al. 2006 (EORTC 20981)

Level of Evidence: Phase III

21-day cycles x 6 cycles

Responders (PR or CR) were randomized to maintenance rituximab or no further treatment.

References

  1. Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. link to original article contains protocol PubMed
  2. Update: Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. link to original article PubMed
  3. van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. link to original article contains verified protocol PubMed
  4. Update: van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. link to original article contains verified protocol PubMed

R-FCM

R-FCM: Rituximab, Fludarabine, Cyclophosphamide, Mitoxantrone

Regimen

Level of Evidence: Phase III

28-day cycles x 4 cycles

Responders (PR or CR) were randomized to maintenance rituximab or no further treatment.

References

  1. Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains verified protocol PubMed
  2. Update: Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. link to original article contains verified protocol PubMed

R-FND

R-FND: Rituximab, Fludarabine, Novantrone, Dexamethasone

Regimen

28-day cycles x up to 8 cycles

References

  1. McLaughlin P, Hagemeister FB, Rodriguez MA, Sarris AH, Pate O, Younes A, Lee MS, Dang NH, Romaguera JE, Preti AH, McAda N, Cabanillas F. Safety of fludarabine, mitoxantrone, and dexamethasone combined with rituximab in the treatment of stage IV indolent lymphoma. Semin Oncol. 2000 Dec;27(6 Suppl 12):37-41. PubMed
  2. P. McLaughlin, M. A. Rodriguez, F. B. Hagemeister, J. Romaguera, A. H. Sarris, A. Younes, N. H. Dang, A. Goy, F. Samaniego, M. Hess, et al. Stage IV indolent lymphoma: A randomized study of concurrent vs. sequential use of FND chemotherapy (fludarabine, mitoxantrone, dexamethasone) and rituximab (R) monoclonal antibody therapy, with interferon maintenance. 2003 ASCO Annual Meeting Abstract 2269. link to abstract contains verified dosages
  3. Hagemeister F, Cabanillas F, Coleman M, Gregory SA, Zinzani PL. The role of mitoxantrone in the treatment of indolent lymphomas. Oncologist. 2005 Feb;10(2):150-9. link to original article PubMed content property of HemOnc.org
  4. Liu Q, Fayad L, Cabanillas F, Hagemeister FB, Ayers GD, Hess M, Romaguera J, Rodriguez MA, Tsimberidou AM, Verstovsek S, Younes A, Pro B, Lee MS, Ayala A, McLaughlin P. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006 Apr 1;24(10):1582-9. link to original article PubMed
  5. G. E. Manoukian, F. B. Hagemeister, P. McLaughlin, L. Fayad, F. Samaniego, A. Goy, J. E. Romaguera, B. Pro, F. Cabanillas, M. A. Rodriguez. Rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) for patients with relapsed indolent B-cell lymphoma (RIL). 2010 ASCO Annual Meeting Abstract 8078. link to abstract contains verified dosages

Rituximab monotherapy

Regimen #1, Witzig et al. 2002; Ghielmini et al. 2004

Level of Evidence: Phase III

4-week course

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose of rituximab
  • Diphenhydramine (Benadryl) 50 mg PO 30 minutes prior to each dose of rituximab

Patients with response or stable disease at 12 weeks in Ghielmini et al. 2004 were randomized to maintenance rituximab or no further treatment.

Regimen #2, Coiffier et al. 2011 (LYM-3001)

Level of Evidence: Phase III

  • Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22 on cycle 1; once on day 1 of subsequent cycles

5-week cycles x 6 cycles

Supportive medications:

  • Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose of rituximab
  • Diphenhydramine (Benadryl) 50 mg PO 30 minutes prior to each dose of rituximab

References

  1. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. link to original article contains verified protocol PubMed
  2. Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. link to original article contains protocol PubMed
  3. Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
  4. Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. doi: 10.1186/1756-8722-5-67. link to original article PubMed

Temsirolimus (Torisel)

Regimen

Level of Evidence: Phase II

28-day cycles x minimum of 2 cycles

References

  1. Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. doi: 10.1200/JCO.2010.29.2813. Epub 2010 Sep 13. link to original article contains verified protocol PubMed

VR

VR: Velcade, Rituximab

Regimen #1, Coiffier, et al. 2011 (LYM-3001)

Level of Evidence: Phase III

  • Bortezomib (Velcade) 1.6 mg/m2 IV push over 3 to 5 seconds once on days 1, 8, 15, 22
  • Rituximab (Rituxan) 375 mg/m2 IV once on days 1, 8, 15, 22 of cycle 1 only; then 375 mg/m2 IV once on day 1 of cycles 2 to 5

35-day cycles x 5 cycles

Supportive medications:

  • No routine antiviral prophylaxis was mandated

Regimen #2, de Vos, et al. 2009

Level of Evidence: Phase II

35-day cycles x 3 cycles

Regimen #3, Agathocleous, et al. 2010

Level of Evidence: Phase II

35-day cycles x up to 6 cycles

References

  1. de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, Flowers CR, Knapp M, Hart L, Patel-Donnelly D, Glenn M, Gregory SA, Holladay C, Zhang T, Boral AL. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023-30. doi:10.1200/JCO.2008.17.7980. Epub 2009 Sep 21. link to original article contains verified protocol PubMed
  2. Agathocleous A, Rohatiner A, Rule S, Hunter H, Kerr JP, Neeson SM, Matthews J, Strauss S, Montoto S, Johnson P, Radford J, Lister A. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol. 2010 Nov;151(4):346-53. doi: 10.1111/j.1365-2141.2010.08340.x. Epub 2010 Sep 29. link to original article contains verified protocol PubMed
  3. Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
  4. Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. doi: 10.1186/1756-8722-5-67. link to original article PubMed

90Yttrium-Ibritumomab-Tiuxetan (Zevalin)

Regimen #1, Witzig, et al. May 2002 - Yttrium-90 and Indium-111

Level of Evidence: Phase III

For patients with relapsed or refractory disease

8-day course of therapy

Regimen #2, Witzig, et al. Aug 2002 - Yttrium-90 only

Level of Evidence: Phase II

For patients with rituximab-refractory disease

8-day course of therapy

References

  1. Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3793-803. link to original article contains verified protocol PubMed
  2. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. link to original article contains verified protocol PubMed
  3. Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-9. link to original article contains verified protocol PubMed
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