Risk - adapted intensive induction therapy, autologous stem cell transplantation, and rituximab maintenance allow to reach a high 7-year survival rate in patients with mantle cell lymphoma

Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among older men. R-CHOP-like regimens allow to achieve high response rate, but the overall survival (OS) are disappointingly short - 3-4 years. An addition of high - dose cytarabine to the upfront therapy and autoSCT significantly improved outcomes but remain feasible largely for medically fit patients. Based on the activity and good tolerance of gemcitabine - oxaliplatin schemes in relapsed and refractory MCL patients, we developed an alternative first - line course for patients who are not eligible for R-HD-MTX-AraC. Aim. Assess toxicity and efficacy of R-DA-EPOCH/ R-HD-MTX-AraC and R-DA-EPOCH/R-GIDIOX schemes, autoSCT and R-maintenance in untreated MCL patients. Materials and methods. 47 untreated MCL patients from 6 centers were enrolled in prospective study between April 2008 and September 2013. All patients have stage II-V; ECOG 0-3; median age 55 years (29-64); Male/Female 76%/24%. MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/ R-HD-MTX-AraC or R-DA-EPOCH/ R-GIDIOX regimen. In the absence of renal failure, hematological toxicity grade 4 more than 3 days and severe infections patients received R-HD-MTX-AraC scheme (R 375 mg/m2 Day 0, Methotrexate 1000 mg/m2/24 hours Day 1, AraC 3000 mg/m2 q 12 hrs Days 2-3). Patients who had at least one of these complications received R-GIDIOX scheme (R 375 mg/m2 day 0, gemcitabine 800 mg/m2 days 1 and 4, ifosfamide 1000 mg/m2 days 1-5, dexamethasone 10 mg/m2 IV days 1-5, irinotecan 100 mg/m2 day 3, oxaliplatin 120 mg/m2 day 2). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Depending on the time of achieving CR patients received 6 or 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Post - transplant R-maintenance was administered for 3 years (R - 375 mg/m2 every 3 months). Results. 29/47 patients were treated on R-HD-MTX-AraC arm (median 50 years; MIPIb: 35.7% low, 28.6% intermediate, 35.7% high risk) and 18/47 patients were on R-GIDIOX arm (median 60 years; MIPIb: 16.7% low, 38.9% intermediate, 44.4% high risk). In R-HD-MTX-AraC arm CR rate was 96.5%. In R-GIDIOX arm OR and CR rates were 94.4% and 77.7% respectively. Main hematological toxicity of R-GIDIOX was leukopenia gr. 4 occurred in 74.1%. With median follow - up of 76 months, the estimated 7-years OS and EFS in R-HD-MTX-AraC arm are 76% and 57% respectively. In R-GIDIOX arm the estimated 7-years OS and EFS are 59% and 44%, respectively. There are no statistical differences in EFS (p=0.47) and OS (p=0.06) between two arms. Conclusions. The use of a risk - adapted strategy allowed 95.7% of patients achieve PR/CR/CRu, performed autoSCT and begun R-maintenance therapy with rituximab. None of the patients needed a premature discontinuation of therapy because of unacceptable toxicity. The performance of autoSCT and R-maintenance apparently allowed to partially offset differences in the intensity of induction therapy and to maintain comparable results of therapy in both induction arms.

mantle cell lymphoma, high dose cytarabine, autoSCT, gemcitabine and oxaliplatin, R-maintenance