Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi

• Published in: British journal of haematology Vol. 156; no. 3; pp. 346 - 353
• Main Authors: Merli, Francesco, Luminari, Stefano, Ilariucci, Fiorella, Petrini, Mario, Visco, Carlo, Ambrosetti, Achille, Stelitano, Caterina, Caracciolo, Francesco, Di Renzo, Nicola, Angrilli, Francesco, Carella, Angelo M., Capodanno, Isabella, Barbolini, Elisa, Galimberti, Sara, Federico, Massimo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012; Blackwell
• Subjects: Adult; Age; Aged; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antibodies, Monoclonal, Murine-Derived - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Autografts; Biological and medical sciences; chemotherapy; Clinical trials; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; cytarabine; Cytarabine - administration & dosage; Cytarabine - adverse effects; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Drug Administration Schedule; Follow-Up Studies; Genetic Markers; Hematologic and hematopoietic diseases; Hematologic Diseases - chemically induced; Humans; Infection - etiology; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Mantle-Cell - drug therapy; Lymphoma, Mantle-Cell - genetics; mantle cell lymphoma; Medical sciences; Methotrexate; Methotrexate - administration & dosage; Methotrexate - adverse effects; Middle Aged; monoclonal antibodies; non-Hodgkin lymphoma; prognostic factors; Prospective Studies; Rituximab; Survival; Toxicity; Treatment Outcome; Vincristine - administration & dosage; Vincristine - adverse effects; Young Adult; Antineoplastic agent; Prognosis; non-Hodgkin lymphoma; prognostic factors; Monoclonal antibody; Antifolate; Cytarabine; Lymphoproliferative syndrome; Immunotherapy; Clinical trial; clinical trials; Methotrexate; Pyrimidine nucleoside; High dose; Human; Hematology; Rituximab; B cell neoplasm; Malignant hemopathy; B-Lymphocyte; Non Hodgkin lymphoma; Chemotherapy; Treatment; Antimetabolic; Mantle cell lymphoma; Cancer; monoclonal antibodies
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2011.08958.x

Summary This study investigated the clinical activity and toxicity of R‐HCVAD‐AM [rituximab plus HyperCVAD (R‐HCVAD) alternating with high‐dose cytarabine and methotrexate (AM)] in patients with newly diagnosed Mantle Cell Lymphoma (MCL). Patients aged ≤70 years with confirmed MCL received four alternating cycles each of R‐HCVAD and AM. Patients who obtained a partial response proceeded to autologous stem cell transplant. Sixty‐three patients were enrolled and 60 were fully eligible. Median age was 57 years (22–66); 60%, 33% and 7% were classified at low (L)‐, intermediate (I)‐ or high (H)‐risk, respectively, according to the MCL International Prognostic Index (MIPI). Only 22 patients (37%) completed the four cycles and three patients died during therapy. Overall response and complete response rates were 83% and 72% respectively. After a median follow‐up of 46 months (range 1–72) the estimated 5‐year overall survival (OS) and progression‐free survival rates were 73% [95% confidence interval (CI) 59–83%], and 61% (95%CI 45–73%) respectively. MIPI maintained the prognostic value with an estimated 5‐year OS of 89%, 80% and 24% for L, I, and H groups respectively (P < 0·001). This multicentre study confirms that R‐HCVAD‐AM is an active regimen for the initial treatment of patients with MCL, but is associated with significant toxicity.