In Vivo Purging with Hyper-CVAD Plus Rituximab Followed by Autologous Stem Cells Transplant and Rituximab Maintenance in Newly Diagnosed Mantle Cell Lymphoma: A Pilot Study for GISL (Italian Cooperative Study Group for Lymphoma).

Previously untreated mantle cell lymphoma (MCL) are consistently associated with poor prognosis when treated with CHOP-like regimens. Typically the CR rate is 20–30%, median FFS = 10–16 months and median OS = 3 years. In the attempt to improve outcome we used a high dose intensity regimen such as Hyper-CVAD (HCVAD) with autologous stem cell transplant (ASCT). Twenty patients entered the study but only 10 up to now are valuable. Patients were apheresed after 2^nd course of HCVAD and if apheresis (LPH) were PCR positive (Bcl1+/JH+) a second set of LPH were performed after completion of 4^th cycle. To perform an in vivo purging Rituximab 375 mg/m² was added at day +1 and +9 after last dose of ARA-C; GCSF 10μg/kg was commenced on day +5 until LPH was ultimated. Rituximab maintenance (375 mg/m² once weekly for 4 consecutive weeks) started 2 month post-ASCT and was repeated every 6 months. Ten patients have completed 4 HCVAD and 7 /10 underwent ASCT and were conditioned with BEAM. After 4 HCVAD 7/10 patients were in CR and 3/7 in PR. After ASCT 1 PR obtained a CR, 1 PD obtained a VGPR and 5 CR maintained CR. Only 4CR post ASCT have received Rituximab maintenance and maintain CR. Two patients (1 CR blastic variant and 1 PR) refused ASCT and after 4 HCVAD received Rituximab maintenance and both are in CCR. Overall with a median follow up of 28.6 months (range 12–51) median survival is not reached. At 4 years 77.8% of patients are alive and PFS is 87.9%. Patients were monitored for bone marrow-MRD by PCR. Eight out of 10 were PCR+ at diagnosis and 7/8 were PCR negative after 4 HCVAD. After ASCT one PCR+ converted to PCR- and 1 PCR+ patient after 4 HCVAD converted to PCR- with Rituximab maintenance (refused ASCT).

Conclusions: high dose intensity regimen HCVAD + Rituximab as in vivo purging and for maintenance allowed to collect tumor free grafts in 70% of PCR+patients at diagnosis and to reach an ORR of 100%, 7/10 CR and PR 3/10 (included 1 blastic variant). PCR negativity was obtained in 7/8 patients. One patient from PR converted to CR after ASCT and one after Rituximab maintenance (without ASCT); thus we might speculate that both high doses (BEAM) and Rituximab do play a role to increase the probability to obtain a CR and PCR-. Survival and PFS of 77.8% and 87.9% respectively at 4 years are encouraging. Further follow up and a higher enrolment of patients are needed to better define the role of HCVAD + Rituximab and ASCT to increase CR,PCR- PFS and OS in MCL.