Efficacy of R-CHOP vs R-CHOP/R-DHAP in Untreated MCL

The aim of this study is to determine whether alternating courses of cyclophosphamide, doxorubicin, vincristine, prednisone/dexamethasone, cytarabine, cisplatin (CHOP/DHAP) plus rituximab followed by total body irradiation \[TBI\]/high dose cytarabine \[ARA-C\]/melphalan-peripheral blood stem cell transplantation (TAM-PBSCT) can improve the time to treatment failure compared to CHOP plus rituximab followed by standard PBSCT (dexamethasone, carmustine, cytarabine, etoposide, and melphalan \[Dexa-BEAM\]/TBI/high dose cyclophosphamide) in patients with untreated mantle cell lymphoma.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* Histologically proven diagnosis of mantle cell lymphoma (World Health Organization \[WHO\] classification)
* Clinical stage II - IV (Ann Arbor)
* Previously untreated patients
* Age 18 - 65 years
* WHO performance \< 2
* Measurable disease (also: patients with isolated bone marrow involvement)
* Informed consent according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use/European Union Good Clinical Practice (ICH/EU GCP) and national/local regulations

Exclusion Criteria:

* Age \> 65 years
* WHO performance status \> 2
* Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
* Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon
* Serious disease interfering with a regular therapy according to the study protocol:

  * cardiac (e.g. manifest heart failure, coronary heart disease, uncontrolled hypertension)
  * pulmonary (e.g. chronic lung disease with hypoxemia)
  * endocrine (e.g. severe, not sufficiently controlled diabetes mellitus)
  * renal insufficiency (unless caused by the lymphoma): creatinine \> 2x normal value and/or creatinine clearance \< 50 ml/min)
  * impairment of liver function (unless caused by the lymphoma): transaminases \> 3x normal or bilirubin \> 2,0 mg/dl
* Patients with unresolved hepatitis B or C infection or known HIV infection
* Prior organ, bone marrow or peripheral blood stem cell transplantation
* Concomitant or previous malignancies within the last 5 years other than basal cell skin cancer or in situ uterine cervix cancer.
* Pregnancy or lactation
* Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule

• BACKGROUNDDreyling 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. doi: 10.1182/blood-2004-10-3883. Epub 2004 Dec 9. PMID 15591112
• BACKGROUNDLenz G, Dreyling M, Hoster E, Wormann B, Duhrsen 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. 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. doi: 10.1200/JCO.2005.08.133. Epub 2005 Jan 24. PMID 15668467
• DERIVEDHermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, Pott C, Salles G, Feugier P, Hubel K, Haioun C, Casasnovas RO, Schmidt C, Bouabdallah K, Ribrag V, Kanz L, Durig J, Metzner B, Sibon D, Cheminant M, Burroni B, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Dreyling M; European Mantle Cell Lymphoma Network. High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023 Jan 20;41(3):479-484. doi: 10.1200/JCO.22.01780. Epub 2022 Dec 5. PMID 36469833
• DERIVEDHermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hanel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Duhrsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. doi: 10.1016/S0140-6736(16)00739-X. Epub 2016 Jun 14.