Mantle cell 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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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? See the main MCL page for current regimens.
Last updated on 2024-07-23:9 regimens on this page
10 variants on this page
 
=First-line therapy=
==CHOP==
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Nickenig et al. 2006 (GLSG '96)	1996-1998 	Phase 3 (C)	MCP 	Might have higher ORR
Lenz et al. 2005 	2000-2002 	Phase 3 (C)	R-CHOP 	Lower ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 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
===References===
# Lenz G, Dreyling M, Hoster E, Wörmann B, Dührsen U, Metzner B, Eimermacher H, Neubauer A, Wandt H, Steinhauer H, Martin S, Heidemann E, Aldaoud A, Parwaresch R, Hasford J, Unterhalt M, Hiddemann W; German Low Grade Lymphoma Study Group. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005 Mar 20;23(9):1984-92. Epub 2005 Jan 24. link to original article EuroPMC
# GLSG '96: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Cyclophosphamide & Fludarabine (FC)==
FC: Fludarabine, Cyclophosphamide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Rule et al. 2015 (CRUK-UCL-MCLIII)	2002-2010 	Phase 3 (C)	FCR 	Shorter OS
====Chemotherapy====
*Fludarabine (Fludara) by the following criteria:
**Standard patients: 40 mg/m2 PO once per day on days 1 to 3
**Patients intolerant of the oral route: 25 mg/m2 IV once per day on days 1 to 3
*Cyclophosphamide (Cytoxan) by the following criteria:
**Standard patients: 250 mg/m2 PO once per day on days 1 to 3
**Patients intolerant of the oral route: 250 mg/m2 IV once per day on days 1 to 3
====Supportive therapy====
*PJP prophylaxis was mandatory
28-day cycle for up to 8 cycles
===References===
# CRUK-UCL-MCLIII: Rule S, Smith P, Johnson PW, Bolam S, Follows G, Gambell J, Hillmen P, Jack A, Johnson S, Kirkwood AA, Kruger A, Pocock C, Seymour JF, Toncheva M, Walewski J, Linch D. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. Haematologica. 2016 Feb;101(2):235-40. Epub 2015 Nov 26. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00641095
==FCR==
FCR: Fludarabine, Cyclophosphamide, Rituximab
 R-FC: Rituximab, Fludarabine, Cyclophosphamide
===Regimen variant #1, 30/250/375===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Kluin-Nelemans et al. 2012 (MCLelderly)	2004-2010 	Phase 3 (E-switch-ic)	R-CHOP 	Shorter OS (secondary endpoint)
====Chemotherapy====
*Fludarabine (Fludara) 30 mg/m2 IV once per day on days 1 to 3
*Cyclophosphamide (Cytoxan) 250 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 (maximum dose of 750 mg) IV once on day 1
28-day cycle for 6 cycles
====Subsequent treatment====
*MCLelderly, responders: Rituximab versus interferon alfa maintenance
===Regimen variant #2, 40/25/375===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Rule et al. 2015 (CRUK-UCL-MCLIII)	2002-2010 	Phase 3 (E-esc)	FC 	Longer OS (primary endpoint)
====Chemotherapy====
*Fludarabine (Fludara) by the following criteria:
**Standard patients: 40 mg/m2 PO once per day on days 1 to 3
**Patients intolerant of the oral route: 25 mg/m2 IV once per day on days 1 to 3
*Cyclophosphamide (Cytoxan) by the following criteria:
**Standard patients: 250 mg/m2 PO once per day on days 1 to 3
**Patients intolerant of the oral route: 250 mg/m2 IV once per day on days 1 to 3
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Supportive therapy====
*PJP prophylaxis was mandatory
28-day cycle for up to 8 cycles
===References===
# MCLelderly: Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, Stilgenbauer S, Thieblemont C, Vehling-Kaiser U, Doorduijn JK, Coiffier B, Forstpointner R, Tilly H, Kanz L, Feugier P, Szymczyk M, Hallek M, Kremers S, Lepeu G, Sanhes L, Zijlstra JM, Bouabdallah R, Lugtenburg PJ, Macro M, Pfreundschuh M, Procházka V, Di Raimondo F, Ribrag V, Uppenkamp M, André M, Klapper W, Hiddemann W, Unterhalt M, Dreyling MH. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012 Aug 9;367(6):520-31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00209209
## Update: Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Geisler CH, Trneny M, Stilgenbauer S, Kaiser F, Doorduijn JK, Salles G, Szymczyk M, Tilly H, Kanz L, Schmidt C, Feugier P, Thieblemont C, Zijlstra JM, Ribrag V, Klapper W, Pott C, Unterhalt M, Dreyling MH. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020 Jan 20;38(3):248-256. Epub 2019 Dec 5. link to original article EuroPMC
# CRUK-UCL-MCLIII: Rule S, Smith P, Johnson PW, Bolam S, Follows G, Gambell J, Hillmen P, Jack A, Johnson S, Kirkwood AA, Kruger A, Pocock C, Seymour JF, Toncheva M, Walewski J, Linch D. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. Haematologica. 2016 Feb;101(2):235-40. Epub 2015 Nov 26. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00641095
==MCP==
MCP: Mitoxantrone, Chlorambucil, Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Nickenig et al. 2006 (GLSG '96)	1996-1998 	Phase 3 (E-switch-ic)	CHOP 	Might have lower ORR
Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2.
====Chemotherapy====
*Mitoxantrone (Novantrone) 8 mg/m2 IV once per day on days 1 & 2
*Chlorambucil (Leukeran) 3 mg/m2 PO three times per day on days 1 to 5
====Glucocorticoid therapy====
*Prednisone (Sterapred) 25 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 to 8 cycles
===References===
# GLSG '96: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==VAD+C==
VAD+C: Vincristine, Adriamycin (Doxorubicin), Dexamethasone, Chlorambucil
===Regimen===
Study 	Evidence
Gressin et al. 2010 (GOELAMS LM1996)	Phase 2
====Chemotherapy====
*Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
*Doxorubicin (Adriamycin) 9 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m2)
*Chlorambucil (Leukeran) 12 mg PO once per day on days 20 to 29
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg IV or PO twice per day on days 1 to 4
35-day cycle for 4 to 8 cycles
====Subsequent treatment====
*GOELAMS LM1996, transplant-eligible patients with more than partial response after 4 cycles: High-dose melphalan & TBI, then autologous HSCT consolidation, 4 weeks after the 6th cycle
===References===
# GOELAMS LM1996: Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
=Maintenance after first-line therapy=
==Interferon alfa monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Dreyling et al. 2004 	1996-2004 	Phase 3 (C)	Cy/TBI, then auto HSCT	Seems to have shorter PFS
Kluin-Nelemans et al. 2012 (MCLelderly)	2004-2010 	Phase 3 (C)	Rituximab 	Shorter combined OS1
1Inferiority was only demonstrated in the group of patients who got R-CHOP first; overall, there was no statistically significant survival difference between the two maintenance groups.
Note: Neither of these trials specified the type of interferon alfa used.
====Preceding treatment====
*R-CHOP induction x 8 versus R-FC induction x 6
====Immunotherapy====
*Interferon alfa
Continued indefinitely
===References===
# Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. link to original article EuroPMC
# MCLelderly: Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, Stilgenbauer S, Thieblemont C, Vehling-Kaiser U, Doorduijn JK, Coiffier B, Forstpointner R, Tilly H, Kanz L, Feugier P, Szymczyk M, Hallek M, Kremers S, Lepeu G, Sanhes L, Zijlstra JM, Bouabdallah R, Lugtenburg PJ, Macro M, Pfreundschuh M, Procházka V, Di Raimondo F, Ribrag V, Uppenkamp M, André M, Klapper W, Hiddemann W, Unterhalt M, Dreyling MH. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012 Aug 9;367(6):520-31. link to original article EuroPMC NCT00209209
## Update: Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Geisler CH, Trneny M, Stilgenbauer S, Kaiser F, Doorduijn JK, Salles G, Szymczyk M, Tilly H, Kanz L, Schmidt C, Feugier P, Thieblemont C, Zijlstra JM, Ribrag V, Klapper W, Pott C, Unterhalt M, Dreyling MH. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020 Jan 20;38(3):248-256. Epub 2019 Dec 5. link to original article EuroPMC
=Relapsed or refractory=
==CHOP (Prednisolone)==
CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Furtado et al. 2014 (NCRN-Ply-26s)	2007-2011 	Randomized Phase 2 (C)	BCHOP 	Shorter OSMedian OS: 11.8 vs 35.6 mo(HR 2.70, 95% CI 1.20-6.25)
Note: this regimen uses prednisolone.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 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====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
===References===
# NCRN-Ply-26s: Furtado M, Johnson R, Kruger A, Turner D, Rule S. Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma. Br J Haematol. 2015 Jan;168(1):55-62. Epub 2014 Aug 22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00513955
==FCM==
FCM: Fludarabine, Cyclophosphamide, Mitoxantrone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Forstpointner et al. 2004	1998-2001 	Phase 3 (C)	R-FCM 	Shorter OS
====Chemotherapy====
*Fludarabine (Fludara) 25 mg/m2 IV over 30 minutes once per day on days 1 to 3
*Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 4 hours on days 1 to 3
*Mitoxantrone (Novantrone) 8 mg/m2 IV over 30 minutes once on day 1
28-day cycle for 4 cycles
====Subsequent treatment====
*Forstpointner et al. 2004, PR/CR: Rituximab maintenance versus no further treatment
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org
## 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. 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 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 	Seems to have shorter OS
====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; 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
Category:Mantle cell lymphoma regimens
Category:Disease-specific pages
Category:Aggressive non-Hodgkin lymphomas
Category:B-cell lymphomas
Category:Historical regimens