Follicular lymphoma

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BR

BR: Bendamustine, Rituximab

Variant #1, Rummel, et al. 2005

• Rituximab (Rituxan) 375 mg/m2 IV on day 1

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

• Bendamustine (Treanda) 90 mg/m2 IV over 30 minutes on days 1 & 2 of cycles 1-4
• Rituximab (Rituxan) 375 mg/m2 IV on day 1 of cycles 1-5

28-day cycles x 5 cycles

Variant #2, Robinson, et al. 2008

• Rituximab (Rituxan) 375 mg/m2 IV once

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

• Bendamustine (Treanda) 90 mg/m2 IV on days 2 & 3
• Rituximab (Rituxan) 375 mg/m2 IV on day 1

28-day cycles x 4 cycles

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

• Rituximab (Rituxan) 375 mg/m2 IV once

Variant #3, Rummel, et al. 2012 - StiL NHL1

• Bendamustine (Treanda) 90 mg/m2 IV on days 1 & 2
• Rituximab (Rituxan) 375 mg/m2 IV on day 1

28-day cycles x up to 6 cycles

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 protocol PubMed
3. 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

BVR

BVR: Bendamustine, Velcade, Rituximab

Regimen #1, Friedberg, et al. 2011

• Bendamustine (Treanda) 90 mg/m2 IV over 30-60 minutes on days 1 & 4, given last
• Bortezomib (Velcade) 1.3 mg/m2 IV push on days 1, 4, 8, 11, given first
• Rituximab (Rituxan) 375 mg/m2 IV on day 1, given after bortezomib and before bendamustine

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

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

CVP

CVP: Cyclophosphamide, Vincristine, Prednisone

Synonyms: COP, COP protocol 2, VCP

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

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
• Prednisone (Sterapred) 40 mg/m2 PO on days 1-5

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

Cyclophosphamide (Cytoxan)

Regimen

• Cyclophosphamide (Cytoxan) 100 mg/m2 PO daily, 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 protocol PubMed

CHOP -> Tositumomab & I-131 (Bexxar)

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

CHOP

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
• Prednisone (Sterapred) 100 mg PO on days 1-5

21-day cycles x 6 cycles

Supportive medications:

• Allopurinol (Aloprim) 300 mg PO daily for patients with bulky disease

Tositumomab & I-131 (Bexxar) dosimetric step

• On Day 0, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution
• Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
• Day 6 or 7: Third scan of whole body dosimetry & redistribution

Tositumomab & I-131 (Bexxar) therapeutic step

• Any day from day 7-14, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3

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 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO daily 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 protocol PubMed
2. 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

FCMR

FCMR: Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab

Regimen

• Fludarabine (Fludara) 25 mg/m2 IV over 30 minutes on days 1-3
• Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 4 hours on days 1-3
• Mitoxantrone (Novantrone) 8 mg/m2 IV over 30 minutes on day 1
• Rituximab (Rituxan) 375 mg/m2 IV on day 0

28-day cycles x 4 cycles

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 protocol PubMed

Fludarabine (Fludara) & Rituximab (Rituxan)

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV on days 1 & 4

Cycle 1 begins 72 hours after the second dose of rituximab

• Fludarabine (Fludara) 25 mg/m2 IV on days 1-5 of cycles 1-6
• Rituximab (Rituxan) 375 mg/m2 IV given 72 hours before cycle 2 day 1, 72 hours before cycle 4 day 1, and 72 hours before cycle 6 day 1
• Rituximab (Rituxan) 375 mg/m2 IV on days 1 & 4 of cycle 7

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

Rituximab (Rituxan), Ibritumomab tiuxetan & Yttrium-90 (Zevalin)

Regimen #1, Morschhauser, et al. 2008

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

• Rituximab (Rituxan) 250 mg/m2 IV on days 1 & 8
• Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 14.8 MBq/kg (maximum dose of 1184 MBq) IV slow push over 10 minutes on day 8 immediately following rituximab

8-day course of therapy

Regimen #2, Witzig, et al. Aug 2002

For patients with rituximab-refractory disease

• Rituximab (Rituxan) 250 mg/m2 IV on days 1 & 8
• Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes on day 8 immediately following rituximab

8-day course of therapy

Regimen #3, Witzig, et al. May 2002

For patients with relapsed or refractory disease

• Rituximab (Rituxan) 250 mg/m2 IV on days 1 & 8
• Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi IV over 10 minutes on day 1
• Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes on day 8 immediately following rituximab

8-day course of therapy

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 protocol PubMed
2. 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 protocol PubMed
3. 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

O-CHOP

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

Regimen, Czucman, et al. 2012 - 409 Study

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 3
• Doxorubicin (Adriamycin) 50 mg/m2 IV on day 3
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 3
• Prednisone (Sterapred) 100 mg/m2 PO on days 3-7
• Ofatumumab (Arzerra) 500 mg or 1000 mg IV on day 1

21-day cycles x 6 cycles

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 protocol PubMed

Ofatumumab monotherapy

Regimen, Czucman, et al. 2012 - 405 Study

• Ofatumumab (Arzerra) 300 mg IV on day 1, increased to 1000 mg in 9th week

Weekly until progression or intolerance

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 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

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
• Prednisone (Sterapred) 100 mg/m2 PO on days 1-5
• Rituximab (Rituxan) 375 mg/m2 IV on day 0

21-day cycles x 6-8 cycles

Regimen #2, Czuczman, et al. 1999 & 2004

Level of Evidence: Phase II

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
• Prednisone (Sterapred) 100 mg/m2 PO on days 1-5
• Rituximab (Rituxan) doses given by the following schedule:
  • Rituximab (Rituxan) 375 mg/m2 IV on days -6 & -1 of cycle 1 (7 and 2 days before cycle 1 day 1)
  • Rituximab (Rituxan) 375 mg/m2 IV 2 days before cycle 3 day 1; and 2 days before cycle 5 day 1
  • Rituximab (Rituxan) 375 mg/m2 IV 8 days and 15 days after completion of cycle 6 (i.e. what would be cycle 7 days 8 & 15)

21-day cycles x 6 cycles

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. 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):4711-6. Epub 2004 Oct 13. link to original article PubMed
3. 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

R-CVP

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Level of Evidence: Phase III Improved OS Similar toxicity

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
• Prednisone (Sterapred) 40 mg/m2 PO on days 1-5
• Rituximab (Rituxan) 375 mg/m2 IV on day 1

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

R-FND

R-FND: Rituximab, Fludarabine, Novantrone, Dexamethasone

Regimen

Primary reference was not able to be obtained to verify this regimen

• Fludarabine (Fludara) 25 mg/m2 IV on days 1-3
• Mitoxantrone (Novantrone) 10 mg/m2 IV on day 1
• Dexamethasone (Decadron) 20 mg PO/IV on days 1-5
• Rituximab (Rituxan) 375 mg/m2 IV on day 1

28-day cycles x up to 8 cycles

Supportive medications:

• Prophylactic trimethoprim/sulfamethoxazole, acyclovir (Zovirax), and fluconazole

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
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
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

Rituximab monotherapy

Regimen

• 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

Maintenance regimen #1 (van Oers, et al. 2006 - EORTC 20981)

• Rituximab (Rituxan) 375 mg/m2 IV on day 1

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

Maintenance regimen #2 (Salles, et al. 2011 - PRIMA)

Starts 8 weeks after the last induction treatment

• Rituximab (Rituxan) 375 mg/m2 IV on day 1

8-week cycles x 12 cycles

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):101-6. 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. 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 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
5. 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 PubMed
6. 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

Rituximab + Lenalidomide

Regimen

• Lenalidomide (Revlimid) 20 mg PO daily days 1-21
• Rituximab (Rituxan) 375 mg/m2 IV on day 1

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. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036) link to abstract

Tositumomab & I-131 (Bexxar)

Dosimetric step

• On Day 0, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
  • First scan of whole body dosimetry & redistribution
• 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

• Any day from day 7-14, infusions of:
  • Tositumomab 450 mg IV over 1 hour
  • Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
    • 65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3

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 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 protocol PubMed
2. 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 protocol PubMed
3. 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
4. Tositumomab and I-131 (Bexxar) package insert

VR

VR: Velcade, Rituximab

Regimen - LYM-3001

• Bortezomib (Velcade) 1.6 mg/m2 IV push on days 1, 8, 15, 22
• Rituximab (Rituxan) 375 mg/m2 IV on days 1, 8, 15, 22 (cycle 1); day 1 only (cycles 2-5)

35-day cycles x 5 cycles

Supportive medications:

• No routine antibiotic or antiviral prophylaxis was mandated

References

1. 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 protocol PubMed
2. 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 protocol PubMed