Short course of R-HyperCVAD/MTX/ARA-C followed by ASCT as first-line therapy in mantle cell lymphoma patients prolongs progression-free survival to more than 9 years

Introduction: Mantle cell lymphoma (MCL) is considered an incurable disease with an historical median OS around 3-4 years with short PFS periods. Regimens that include high-dose cytarabine and consolidation with autologous stem-cell transplant (ASCT) have become standard therapy for fit patients. The median PFS reported after 4-6 cycles HyperCVAD followed by ASCT consolidation is 4.5 years (Ahmadi et al., BMT 2012). Nevertheless, toxicity is high and many patients cannot obtain stem cells for transplant. In this setting, some groups use 6-8 cycles R-HyperCVAD without ASCT consolidation, achieving the same median PFS of 4.6 years (Romaguera et al., Br J Hematol 2010). We present our experience treating fit patients with MCL in first line with a short course of 2 cycles of R-HyperCVAD followed by consolidation with ASCT. Methods: From January 2002 to August 2016, all patients diagnosed with MCL treated in first line with a short course of 2 cycles of R-HyperCVAD and ASCT were included in this retrospective analysis. International working group response assessment criteria were used. Results: 85 MCL patients were registered: 7(8.2%) did not receive immediate therapy, 44(52.4%) were not eligible for intensive therapy and 33 (39.3%) were treated with R-HyperCVAD. Characteristics at diagnosis of these 33 patients: M/F ratio: 26/7 (78.8%/21.2%), median age: 63(40-73) y.o, ECOG 0-1: 26(86.7%), Ann Arbor stage III-IV 28/31 (90.3%), MIPI score: low: 5(16.7%), intermediate: 17(56.7%) and high risk: 8(26.7%). Thirty (90.9%) patients completed 2 cycles of R-HyperCVAD. Discontinuation causes were: 2 deaths for sepsis and 1 CNS progression. Intention to treat response rate was: CR 26 (78.8%), PR 2, (6.0%), progressive disease 3 (9.0%) and not evaluable 2 (6.0%). Among the 28 patients in CR/PR considered eligible for ASCT consolidation, 8 patients were not transplanted: 4(14.3%) had harvest failure (no plerixafor availability), 2 persistent toxicity, 1 rejected, 1 unknown cause. Conditioning regimen was BEAM/LACE in 18 (90%) patients and cyclophosphamide-TBI in 2(10%). One patient died 10 days after infusion because of a septic episode. With a median follow-up of 35 (1-131) months, the median PFS was 73.0 (95% CI, 38.2-107.8) months (6.08 years) for the whole group, 114 (47.3-180.7) months (9.4 years) for the transplanted patients vs 21 (3.1-38.9) months (1.8 years) for the non-transplanted group. The median OS was 123 (31.9-214.1) months. Median OS was not reached for the transplanted group vs 31.0 (7.5-54.6) months for non-transplanted group. Conclusion: A short course of R-HyperCVAD achieves a very high remission rate in fit MCL patients. Two thirds of the patients completed the planned therapy with ASCT consolidation. Those patients have an excellent outcome with a PFS of more than 9 years. Keywords: autologous stem cell transplantation (ASCT); hyper-CVAD; mantle cell lymphoma (MCL)