The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexatecytarabine followed by consolidation with 90 Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of 90 Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twentyfour patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60-93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4-59.6), 52% (95% confidence interval 32.4-71.6) and 81% (95% confidence interval 67.28-94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48-78.52) and 87% (95% confidence interval 70-100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3-4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with 90 Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

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Introduction: Indolent B cell non-Hodgkin lymphomas are entities without curative treatment nowadays. However, survival has significantly improved since the incorporation of immunomodulatory agents and now immunochemotherapy has become the gold standard. Most treatment strategies use progression free survival (PFS) as a surrogate marker for overall survival (OS), although updated long term results are frequently lacking. Since 1990 our group introduced IFNα-2b to Bagley’s CVP induction regimen, for naïve indolent NHL (LNH-pro study). Herein we report our long term results. Aim: To evaluate long term outcome and late toxicities of patients who received immunochemotherapy with IFN α-2b plus CVP. Patients and Methods: From February 1990 to November 2001, patients from 7 Spanish institutions were included. Induction therapy consisted of Cyclophosphamide (400 mgs/m2 po) and Prednisone (100 mg/m2 po) daily for 5 days, Vincristine (1.4mg/m2 iv) on day 1, and subcutaneous IFN α-2b (3 MU/m2, three times a week, for a total of 36 doses). Patients received the number of cycles necessary to achieve maximum response. Updated clinical data were retrieved from participating centres up to March 2012. Results. A hundred and seventy patients with low-grade NHL were analyzed. Included entities were: 65% grade 1-2 follicular lymphoma (FL), 21% lymphocytic lymphoma and 14% marginal zone lymphoma. Median age was 56 yo (range 22-78 yo), elevated LDH and β2-microglobuline were 13.6% and 26% respectively, 57.6% had bone marrow involvement and 7.6% bulky disease (>7cm). According to FLIPI, 33% were high risk, 40% intermediate and 27% low risk FL. Median number of cycles was 6, and overall response rate achieved was 90%, with 68% complete remissions. Median follow up of surviving patients was 12.5 years (range 3-21 ys), with only 14.7% of patients lost to follow-up. Median PFS for all patients was 12.5 years (95% CI 10.5 – 14.5 years) and not reached for FL patients (20-year PFS of 63%; 95%CI: 54-72%). Median OS has not been reached, with a 20-year OS of 59.7% (CI 95%, 50.5-69%) for all low-grade NHL patients and 62% (IC 95%, 50-74%) for FL patients. Long-term toxicity is detailed in table 1. Incidence of secondary malignancies is 13.5%. At time of analysis, 57 out of 170 patients have died (33.5%), mainly due to lymphoma (58% of patients) and other non-lymphoma events (42%). Table Secondary malignancies 23 cases (13.5%) - MDS / AML 3 cases - Solid tumors 18 cases - Dermatologic neoplasia 2 cases Causes of death Number of patients (%) Induction toxicity events 4 (7%) Lymphoma progression / relapse 29 (51%) Secondary malignancies 9 (16%) Other non-lymphoma events 15 (26%) - Miocardiopathy 4 - Chronic Pulmonary disease 3 - Hepatic failure 2 - Brain traumatic injury 1 - Unknown cause 5 Figure 1 Figure 1. Conclusions: Our results confirm that immunochemotherapy with IFN α-2b plus CVP regimen induces a median PFS of 12.5 years and a 20-year OS of 59.7% (median not reached). With a median follow-up of 12.5 years, 58 % died due to lymphoma, 16% from secondary malignancies and 26% for non-lymphoma events. These results highlight the importance of performing long term follow-up in order to assess the real survival benefit of any treatment. Disclosures No relevant conflicts of interest to declare.

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