First Line Treatment with the R-VAD+C Regimen Followed by ASCT for Patients under 65 with a Mantle Cell Lymphoma (MCL). From the GOELAMS Group.

This protocol followed the first GOELAMS protocol (also presented at ASH 2006) for MCL pts testing the addition of Rituximab with the VAD+C regimen followed by ASCT. Thirty nine pts were included in this phase II prospective study opened between January 2003 and December 2005.

Inclusion criteria: MCL by the WHO (common or blastoïd variants), under 65 years with PS under 3, who never received chemotherapy.

Treatment: the first step consist of 4 courses of R-VAD+C regimen (J1, Rituximab 375 mg/sqm; J1 to J4, Vincristin 0,4 mg/D, Adriblastin 9 mg/D and Dexamethasone 40 mg/D; J20 to J29 Chlorambucil 12 mg/D) every 35 days. Evaluation after 4 cycles with the Cheson criterias. Responders (at least 50%) have been collected after a 4 g/sqm cyclophosphamide stimulation and an in vivo purge with rituximab (375). Then, the second step consisted on one R-VAD+C and one VAD+C regimens followed by the transplantation prepared by the myeloablative regimen including Alkeran 140 mg/sqm and 8 grays/4 fr TBI.

Results: 38/39 pts are evaluable. 34 biopsies were reviewed and consisted of 26 common forms and 8 blastoïd variants. 4 other diagnosis were possible only on blood (n=3) or bone marrow (n=1) analysis.

Treatment: 28/38 (74%) have had a response to the first 4 R-VAD+C, 6 progressed (16%) and 4 (10%) have had only a minor response under 50%. 17/38pts (44,5%) were in CR or CRu after 4 R-VAD+C courses and 11 (29%) in PR>50%. Among the 23 pts evaluated after the transplantation, 20 were in CR, two progressed and one have a PR>50%.

Survival: With a median follow-up of 19 months, OS and PFS at 2 years are 80% and 50 % respectively. The PFS is significantly affected by the Goelams Index for MCL described recently from a cohort of patients studied in our previous protocol (see abstract ASH 2006).

Conclusion The R-VAD+C regimen followed by PBSCT is a good sequence for the treatment in first line of MCL patients, especially for those with a good prognosis profile defined by the new Goelams prognostic index which would worth being tested on a larger cohort.