Immuno-Chemotherapy (IC) and Autologous Stem Cell Transplant (ASCT) for Untreated Patients (pts) with Mantle Cell Lymphoma (MCL): CALGB 59909.

We evaluated the feasibility, safety, and effectiveness of an intense IC regimen including ASCT in pts with untreated MCL up to age 70. The primary end-point was 2-year progression free survival (PFS). A successful protocol would demonstrate a 2-year PFS of 50% (95% CI 37, 63%) or better. MCL was confirmed by central pathology review plus either compatible immunophenotype, cyclin D1 over-expression, t(11;14) or bcl-1/IgH rearrangement. Treatment consisted of 2 cycles (3 if marrow has >=15% MCL after 2 cycles) of rituximab (R), methotrexate 300 mg/m2 (M) and augmented CHOP (2 g/m2 cyclophosphamide [C]) followed by consolidation and stem cell collection with EAR (etoposide [E] 40 mg/kg, cytarabine [A] 2 g/m2 for 8 doses, R for 2 doses, and filgrastim 10 mcg/kg/day beginning day14 until completion of stem cell collection). EAR was followed by ASCT using CBV (carmustine [B] 15 mg/kg, E 60 mg/kg, and C 100 mg/kg) followed by R 6 and 7 weeks after ASCT. 79 pts were enrolled in 40 months: median age 57 (37–69); 79% male; 33% elevated serum LDH; 73% bone marrow (+); 5% cerebrospinal fluid (+). 1 pt never received protocol therapy, 1 pt came off study for an allogeneic stem cell transplant, and 7 pts never underwent ASCT. Stem cell collection was excellent, with a median CD34-cell dose of 12x106/kg in median of 1 apheresis. There were 2 treatment-related deaths. The complete and partial response rates were 62% (49,74%) and 27% (17, 40%), respectively. With a median follow-up of 27.5 months, the PFS is 75% (61, 84%) at 2 years and 56% (39, 69%) at 3 years (intention to treat analysis). The overall survival is 82% (68, 90%) at 3 years. Intense IC plus ASCT is feasible, safe, and effective in pts with MCL. These results are comparable to single institution outcomes. Maintenance bortezomib will be added to this regimen post-ASCT in a successor CALGB trial.