Indolent lymphoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? Please go to the main iNHL regimen page to find other regimens.
Last updated on 2024-12-02:16 regimens on this page
19 variants on this page
=First-line therapy=
==COPA==
COPA: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Adriamycin (Doxorubicin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
O'Connell et al. 1987 	1978-1983 	Phase 3 (C)	1. COPA-B2. CAP-BOP	Did not meet efficacy endpoints
Smalley et al. 1992 (ECOG E6484)	1985-1988 	Phase 3 (C)	I-COPA 	Shorter TTTF
Note: this regimen is very similar but distinct from CHOP. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.2 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
28-day cycle for 8 cycles
===References===
# O'Connell MJ, Harrington DP, Earle JD, Johnson GJ, Glick JH, Carbone PP, Creech RH, Neiman RS, Mann RB, Silverstein MN; ECOG. Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma. J Clin Oncol. 1987 Sep;5(9):1329-39. link to original article EuroPMC
# ECOG E6484: Smalley RV, Andersen JW, Hawkins MJ, Bhide V, O'Connell MJ, Oken MM, Borden EC. Interferon alfa combined with cytotoxic chemotherapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1336-41. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==CVP==
CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
VCP: Vincristine, Cyclophosphamide, Prednisone
===Regimen variant #1, 750/1.4/40===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy 	Comparative Toxicity
Hagenbeek et al. 2006 	1993-1997 	Phase 3 (C)	Fludarabine	Did not meet primary endpoint of PFS48	Less toxic
Marcus et al. 2004 (M39021)	2000-2002 	Phase 3 (C)	R-CVP 	Shorter TTP 	Similar toxicity
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for up to 8 cycles
===Regimen variant #2, 1000/1.4/100===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hochster et al. 2009 (ECOG E1496)	Not reported 	Phase 3 (C)	FC 	Not reported
Note: the FC arm was closed prematurely and comparisons between CVP and FC were not conducted.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
====Subsequent treatment====
*Rituximab maintenance versus observation
===Regimen variant #3, 2000/1.4/100===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Unterhalt et al. 1996	1989-04 to 1996-01 	Phase 3 (C)	PmM 	Seems to have shorter EFS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 400 mg/m2 (route not specified) once per day on days 1 to 5
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 (route not specified) once per day on days 1 to 5
21-day cycle for 6 cycles
====Subsequent treatment====
*Unterhalt et al. 1996, responders: COP continuation x 2 (8 total), then interferon alfa maintenance versus observation
===References===
# Unterhalt M, Herrmann R, Tiemann M, Parwaresch R, Stein H, Trümper L, Nahler M, Reuss-Borst M, Tirier C, Neubauer A, Freund M, Kreuser ED, Dietzfelbinger H, Bodenstein H, Engert A, Stauder R, Eimermacher H, Landys K, Hiddemann W; German Low-Grade Lymphoma Study Group. Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. Leukemia. 1996 May;10(5):836-43. EuroPMC
## Update: Hiddemann W, Unterhalt M, Herrmann R, Wöltjen HH, Kreuser ED, Trümper L, Reuss-Borst M, Terhardt-Kasten E, Busch M, Neubauer A, Kaiser U, Hanrath RD, Middeke H, Helm G, Freund M, Stein H, Tiemann M, Parwaresch R. Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol. 1998 May;16(5):1922-30. link to original article EuroPMC
# M39021: 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. Epub 2004 Oct 19. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## Update: 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 EuroPMC
# Hagenbeek A, Eghbali H, Monfardini S, Vitolo U, Hoskin PJ, de Wolf-Peeters C, MacLennan K, Staab-Renner E, Kalmus J, Schott A, Teodorovic I, Negrouk A, van Glabbeke M, Marcus R. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol. 2006 Apr 1;24(10):1590-6. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# ECOG E1496: 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. Epub 2009 Mar 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00003204
## Update: Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. link to original article link to PMC article EuroPMC
==Fludarabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Zinzani et al. 2000	1995-1998 	Phase 3 (C)	Fludarabine & Idarubicin	Higher CR rate1
1The superiority of this arm was only observed in the FL subgroup; overall, there was no statistically significant difference between arms.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV over 30 minutes once per day on days 1 to 5
28-day cycle for 6 cycles
===References===
# Zinzani PL, Magagnoli M, Moretti L, De Renzo A, Battista R, Zaccaria A, Guardigni L, Mazza P, Marra R, Ronconi F, Lauta VM, Bendandi M, Gherlinzoni F, Gentilini P, Ciccone F, Cellini C, Stefoni V, Ricciuti F, Gobbi M, Tura S. Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma. J Clin Oncol. 2000 Feb;18(4):773-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cyclophosphamide & Fludarabine (FC)==
FC: Fludarabine & Cyclophosphamide
CF: Cyclophosphamide & Fludarabine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hochster et al. 2009 (ECOG E1496)	Not reported 	Phase 3 (E-switch-ic)	CVP 	Not reported
Note: investigation into this regimen was halted due to excess mortality.
====Chemotherapy====
*Fludarabine (Fludara) 20 mg/m2 IV once per day on days 1 to 5
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
28-day cycle for up to 8 cycles
====Subsequent treatment====
*Rituximab maintenance versus observation
===References===
# ECOG E1496: 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. Epub 2009 Mar 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00003204
==FND==
FND: Fludarabine, Novantrone (Mitoxantrone), Dexamethasone
===Regimen===
Study 	Dates of enrollment	Evidence
McLaughlin et al. 1996	1992-01 to 1993-12 	Phase 2
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 3
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg/day IV or PO on days 1 to 5
28-day cycle for up to 8 cycles
===References===
# McLaughlin P, Hagemeister FB, Romaguera JE, Sarris AH, Pate O, Younes A, Swan F, Keating M, Cabanillas F. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol. 1996 Apr;14(4):1262-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==ProMACE-MOPP==
ProMACE-MOPP: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone
===Regimen===
Study 	Evidence 	Comparator
Young et al. 1988	Phase 3 (E-esc)	Watchful waiting
Note: Treatment details are not available for online review.
====Chemotherapy====
*Methotrexate (MTX)
*Doxorubicin (Adriamycin)
*Cyclophosphamide (Cytoxan)
*Etoposide (Vepesid)
*Mechlorethamine (Mustargen)
*Vincristine (Oncovin)
*Procarbazine (Matulane)
====Glucocorticoid therapy====
*Prednisone (Prolix)
*Prednisone (Sterapred)
===References===
# Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. does not contain dosing details in abstract EuroPMC
=Relapsed or refractory=
==Copanlisib monotherapy==
===Regimen variant #1, flat dose===
Study 	Dates of enrollment 	Evidence 	Efficacy
Dreyling et al. 2017 (CHRONOS-1)	2012 to not reported	Phase 2 (RT)	ORR: 59% (95% CI, 49-68)
Note: this was the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the 2017 publication only detailed the weight-based dosing (see below). The 2021 subgroup analysis did describe this dosing.
====Targeted therapy====
*Copanlisib (Aliqopa) 60 mg IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
===Regimen variant #2, weight-based===
Study 	Dates of enrollment 	Evidence 	Efficacy
Dreyling et al. 2017 (CHRONOS-1)	2012 to not reported	Phase 2 (RT)	ORR: 59% (95% CI, 49-68)
====Targeted therapy====
*Copanlisib (Aliqopa) 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
===References===
#CHRONOS-1: Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01660451
##Subgroup analysis: Panayiotidis P, Follows GA, Mollica L, Nagler A, Özcan M, Santoro A, Stevens D, Trevarthen D, Hiemeyer F, Garcia-Vargas J, Childs BH, Zinzani PL, Dreyling M. Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma. Blood Adv. 2021 Feb 9;5(3):823-828. link to original article link to PMC article EuroPMC
==Copanlisib & Rituximab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Matasar et al. 2021 (CHRONOS-3)	2015-2019 	Phase 3 (E-esc)	Rituximab 	Longer PFS (primary endpoint)Median PFS: 21.5 vs 13.8 mo(HR 0.52, 95% CI 0.39-0.69)
====Targeted therapy====
*Copanlisib (Aliqopa) 60 mg IV over 60 minutes once per day on days 1, 8, 15, given first
*Rituximab (Rituxan) given second as follows:
**Cycle 1: 375 mg/m2 IV once per day on days 1, 8, 15, 22
**Cycles 3, 5, 7, 9: 375 mg/m2 IV once on day 1
28-day cycles
===References===
#CHRONOS-3: Matasar MJ, Capra M, Özcan M, Lv F, Li W, Yañez E, Sapunarova K, Lin T, Jin J, Jurczak W, Hamed A, Wang MC, Baker R, Bondarenko I, Zhang Q, Feng J, Geissler K, Lazaroiu M, Saydam G, Szomor Á, Bouabdallah K, Galiulin R, Uchida T, Mongay Soler L, Cao A, Hiemeyer F, Mehra A, Childs BH, Shi Y, Zinzani PL. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):678-689. Epub 2021 Apr 10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02367040
==Fludarabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Klasa et al. 2002	1993-1996 	Phase 3 (E-switch-ic)	CVP 	Seems to have longer PFS
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 5
28-day cycles
===References===
# Klasa RJ, Meyer RM, Shustik C, Sawka CA, Smith A, Guévin R, Maksymiuk A, Rubinger M, Samosh M, Laplante S, Grenier JF. Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen. J Clin Oncol. 2002 Dec 15;20(24):4649-54. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Fludarabine & Rituximab (FR)==
FR: Fludarabine & Rituximab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Rummel et al. 2015 (StiL NHL 2-2003)	2003-2010 	Phase 3 (C)	BR 	Shorter PFS
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 (route not specified) once per day on days 1 to 3
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
28-day cycle for up to 6 cycles
===References===
# StiL NHL 2-2003: Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT01456351
==FMP==
FMP: Fludarabine, Mitoxantrone, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Zinzani et al. 1995a	1993-11 to 1994-06 	Phase 2
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV once per day on days 1 to 3
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg IV once per day on days 1 to 5
21-day cycle for up to 6 cycles
===References===
# Zinzani PL, Bendandi M, Tura S. FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):262-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Idelalisib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Gopal et al. 2014 (DELTA)	2011-2012 	Phase 2 (RT)
====Targeted therapy====
*Idelalisib (Zydelig) 150 mg PO twice per day
Continued indefinitely
===References===
#DELTA: Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01282424
##Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. link to abstract
==Interferon alfa monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Foon et al. 1984	Not reported 	Phase 2
====Immunotherapy====
*Interferon alfa
===References===
# Foon KA, Sherwin SA, Abrams PG, Longo DL, Fer MF, Stevenson HC, Ochs JJ, Bottino GC, Schoenberger CS, Zeffren J, Jaffe ES, Oldham RK. Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A interferon. N Engl J Med. 1984 Nov 1;311(18):1148-52. link to original article EuroPMC
==131Iodine-Tositumomab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Kaminski et al. 1993 	Not reported 	Non-randomized, fewer than 20 pts
Press et al. 1995 	Not reported 	Phase 2
Kaminski et al. 2001 (RIT-II-004)	1996-1998 	Phase 2 (RT)
Horning et al. 2004 (CP-97-012) 	1998-1999 	Phase 2 (RT)
Olney et al. 2014 (SB-393229/032)	2004-2007 	Phase 2
Note: Kiminski et al. 1993 and Press et al. 1995 are included here for historic context but had different treatment details.
====Radioconjugate therapy, 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
====Radioconjugate therapy, therapeutic step====
*Any day from day 7 to 15, 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 to 150,000/mm3
Calculated dose of I-131 is based on information from serial total-body gamma-camera counts
====Supportive therapy, therapeutic step====
*Acetaminophen (Tylenol) 650 mg PO as premedication for Tositumomab and I-131 (Bexxar)
*Diphenhydramine (Benadryl) 50 mg PO as premedication for Tositumomab and I-131 (Bexxar)
*Potassium iodide (SSKI, saturated solution of potassium iodide) 2 drops PO three times per day 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===
# Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD, Crawford SM, Burgess JM, Petry NA, Butchko GM, Glenn SD, Wahl RL. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993 Aug 12;329(7):459-65. link to original article EuroPMC
# Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S, Fisher DR, Porter B, Matthews DC, Gooley T, Bernstein ID. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet. 1995 Aug 5;346(8971):336-40. link to original article EuroPMC
# RIT-II-004: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# CP-97-012: Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005 Feb 1;23(4):712-9. Epub 2004 Dec 21. link to original article EuroPMC
# Meta-analysis: 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 EuroPMC
# SB-393229/032: Olney HJ, Freeman MA, Stewart DA, Mangel JE, White DJ, Elia-Pacitti JO. Prolonged progression-free survival and preserved quality of life in the Canadian prospective study of tositumomab and iodine(131)-tositumomab for previously treated, rituximab-exposed, indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2014 Dec;55(12):2754-60. Epub 2014 Apr 3. link to original article EuroPMC NCT00240565
==Ofatumumab monotherapy==
===Regimen=== 
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Maloney et al. 2020 (HOMER)	2010-2016 	Phase 3 (E-switch-ic)	Rituximab 	Did not meet primary endpoint of PFS
Note: there was no MTD determined in Hx-CD20-001.
====Targeted therapy====
*Ofatumumab (Arzerra) as follows:
**Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
**Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22
====Supportive therapy====
*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
28-day cycle for 2 cycles
===References===
#HOMER: Maloney DG, Ogura M, Fukuhara N, Davis J, Lasher J, Izquierdo M, Banerjee H, Tobinai K. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 2020 Aug 25;4(16):3886-3893. link to original article link to PMC article EuroPMC NCT01200589
==Umbralisib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Fowler et al. 2021 (UNITY-NHL)	2017-2018 	Phase 2b (RT)
====Targeted therapy====
*Umbralisib (Ukoniq) 800 mg PO once per day on days 1 to 28, taken with food
28-day cycles
===References===
#UNITY-NHL: Fowler NH, Samaniego F, Jurczak W, Ghosh N, Derenzini E, Reeves JA, Knopińska-Posłuszny W, Cheah CY, Phillips T, Lech-Maranda E, Cheson BD, Caimi PF, Grosicki S, Leslie LA, Chavez JC, Fonseca G, Babu S, Hodson DJ, Shao SH, Burke JM, Sharman JP, Law JY, Pagel JM, Miskin HP, Sportelli P, O'Connor OA, Weiss MS, Zinzani PL. Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2021 May 20;39(15):1609-1618. Epub 2021 Mar 8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02793583
Category:Indolent lymphoma regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Indolent lymphomas
Category:B-cell lymphomas