Feasability and Toxicity After Induction Treatment with Rituximab-HCVAD and Metotrexate/Citarabine, Followed by Consolidation with Y-90 Ibritumomab Tiuxetan (Phase II GELTAMO–LCM 04-02 study).

Mantle Cell Lymphoma (MCL) is an entity with a median survival of 2- 4 years, so it is currently considered an aggressive tumour. Standard chemotherapies for other B cell lymphomas have yielded poor results. Better outcomes have been communicated with the use of up front intensive chemotherapy or of high doses schemas with stem cell support as consolidation of the response, although relapses frequently occur. Keeping in mind these considerations, we used the Hyper-CVAD/MTX-AraC squema in association with anti-CD20, followed by consolidation with Ibritumomab-tiuxetan (Zevalin^R) with the aim of eradicating minimal residual disease and decrease the risk of relapse.

Evaluate the feasibility, safety and, efficacy for overall response, complete response and progression free survival (PFS) in newly diagnosed MCL patients with advanced Ann Arbor stage or with lower stage but with B symptoms or bulky disease.

All patients received: Anti-CD20/Hyper-CVAD therapy alternating with anti-CD20/MTX/Ara-C, supported with Peg- Filgastrim. Response was evaluated after 4 cycles and, treatment continued up to a median of 6 cycles if response (complete or partial) was achieved. Consolidation treatment consisted in a single dose of Y90-Ibritumomab-Tiuxetan (Zevalin) (RIT) administered 8 to 12 weeks after the last cycle. We started at a dose of 0.3 mCi/kg with a planned dose escalation to 0.4 mCi/kg if no unacceptable toxicity was observed in the 1st three patients treated.

From February 2006 until July 2008, 30 patients were enrolled. Patients' characteristics: 77% male, median age of 59 years old (range 41-70), 93.3% Ann Arbor stage IV, 87% bone marrow infiltration, 62% gastrointestinal infiltration and 13%were blastic variant. Induction therapy: The main toxicities over 170 cycles were haematological and greater in the odd cycles (90% vs 53% grade 3-4 Neutropenia and 98% v. 33% grade 3-4 thrombocytopenia). Sixty five SAEs were reported during induction, mainly neutropenic fever and upper tract respiratory infection with 1 death due to sepsis (3.3%), and 5 non-related events (including 1 suicide). Response after induction: 20 patients (66,7%) were in CR, 5 (16,7%) in uRC, 1 (3,3%) progressed, and 4 patients (13,3%) were not evaluable due to early events (2 deaths and 2 toxicities). Consolidation with RIT: dose of RIT was fixed at 0.3 mCi/Kg after treatment of the first 6 patients and total of 18 patients (60%) have finally received it. Grade 3-4 neutropenia and thrombopenia was observed in 72% and 83% of the patients with a median duration of 3 and 8 weeks, respectively. Ten SAEs with no deaths were reported after consolidation. Twelve patients (40%) could not accomplish the whole treatment due to following reasons: 8 because of induction toxicity (5 infection with one death, 1 neurological, 3 delayed haematological recovery); 1 non related death, 1 progression and 1 withdrawal for personal reasons. Survival: With a median follow up of 25 months. Actuarial OS and PFS to 33 months is 90% and 75% respectively.

treatment of MCL with 6 cycles of Hyper-CVAD/MTX-AraC with anti-CD20 can be accomplished in 70% of the patients up to 70 years, although close follow-up and dose adjustments are frequently required mainly due to haematological toxicity. Consolidation with Ibritumomab-tiuxetan is safe and feasible at a dose of 0,3 mCi/Kg. Efficacy is high with an ORR and PFS of 83% and 75%, respectively although longer follow-up is needed to evaluate the role of consolidation treatment with RIT.

Salar:Amgen: Honoraria.