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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main MCL page for current regimens.

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 superior ORR
Lenz et al. 2005 2000-2002 Phase 3 (C) R-CHOP Inferior ORR

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles

References

  1. 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 PubMed
  2. 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 contains dosing details in manuscript PubMed

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 Inferior 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

28-day cycle for up to 8 cycles

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed 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 Inferior OS (secondary endpoint)

Chemotherapy

Targeted therapy

28-day cycle for 6 cycles

Subsequent treatment


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 Superior 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

Supportive therapy

  • PJP prophylaxis was mandatory

28-day cycle for up to 8 cycles

References

  1. 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 contains dosing details in manuscript PubMed NCT00209209
    1. 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 PubMed
  2. 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 contains dosing details in manuscript link to PMC article PubMed 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 inferior 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

Glucocorticoid therapy

28-day cycle for 6 to 8 cycles

References

  1. 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 contains dosing details in manuscript PubMed

VAD+C

VAD+C: Vincristine, Adriamycin (Doxorubicin), Dexamethasone, Chlorambucil

Regimen

Study Evidence
Gressin et al. 2010 (GOELAMS LM1996) Phase 2

Chemotherapy

Glucocorticoid therapy

35-day cycle for 4 to 8 cycles

Subsequent treatment

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed

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 inferior PFS
Kluin-Nelemans et al. 2012 (MCLelderly) 2004-2010 Phase 3 (C) Rituximab Inferior 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

Immunotherapy

Continued indefinitely

References

  1. 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 PubMed
  2. 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 PubMed NCT00209209
    1. 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 PubMed

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 Inferior OS

Note: this regimen uses prednisolone.

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles

References

  1. 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 contains dosing details in manuscript PubMed 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 Inferior OS

Chemotherapy

28-day cycle for 4 cycles

Subsequent 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 dosing details in manuscript PubMed content property of HemOnc.org
    1. 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 contains dosing details in manuscript PubMed

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 inferior OS

Chemotherapy

Targeted therapy

28-day cycle for up to 6 cycles

References

  1. 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 contains dosing details in abstract PubMed NCT01456351
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