Long Term Remission in Follicular Lymphoma (FL) and Mantle Cell Lymphoma (MCL) with Rituximab Consolidation after High-Dose Chemotherapy and Autologous Stem Cell Transplantation: Extended Follow-Up of a Multicenter Phase II Study.

We investigated the efficacy of rituximab given after high-dose therapy (HDT) and autologous peripheral blood stem cell transplantation (ASCT) in order to prevent relapse by clearance of minimal residual disease in patients with advanced FL and MCL. Eligibility included newly diagnosed stage III/IV t(14;18)+ FL or newly diagnosed or relapsed patients with stage III/IV t(11;14)+ MCL. 35% of patients had elevated LDH levels, 23% had B-symptoms. The age-adjusted IPI risk category was low-intermediate in 65% and high-intermediate in 35% of the patients. Initial cytoreduction consisted of VACOP-B (6 weeks) or CHOP chemotherapy, followed by G-CSF supported VIP-(E) or DexaBEAM therapy. PBSC were harvested, and positive selection of CD34+ cells was performed. HDT consisted of TBI (6x2 Gy) and cyclophosphamide (120 mg/kg), followed by CD34+ PBSCT (7.16x106 CD34+/kg; range 2.4–22.7). A median of 62 days (range 38–108) after transplantation, rituximab was given at a dose of 375 mg/m² weekly for 4 weeks. No additional treatment was given thereafter. Between October 1997 and July 2001, 31 patients were included. Median age at transplantation was 49 (31–60) years. One patient died early after HDT due to neutropenic septicemia before rituximab administration. Therefore, only 30 patients were evaluable for safety and efficacy of rituximab after HDT and ASCT (FL n=20, MCL n=10). Twenty seven were evaluable for MRD. In the intent-to-treat (ITT) analysis, 7 treatment failures were observed: two FL patients relapsed at 25 and 33 months post transplant, four MCL patients relapsed at 24, 38, 47 and 48 months post transplant, and one MCL patient died unexpectedly in complete remission (CR) at 19 months post transplant. One of the MCL patients died at 37 months post transplant due to progressive disease. Currently, 28 of 30 patients are alive. With an extended median follow up of 61 months (18.7 – 87.5 months) after ASCT, the progression-free survival (PFS) for the ITT population is 76.7%, the median PFS has not yet been reached. In the FL population, the PFS at 5 years is 90% (95% CI: 65.6 – 97.4) whereas in the MCL population, the PFS is 46.2% (95% CI: 14.7 – 73.3) (log rank p=0.0168). The overall survival (OS) at 5 years for the ITT population is 93.3% (95% CI; 75.6 – 98.3) with 100% OS in the FL patients and 79.4% (95% CI: 39.6 – 94.4) (log rank p=0.0400) in MCL patients. In summary, at an extended follow-up of 5 years, we show that one 4-week course of Rituximab consolidation after HDT and ASCT induces prolonged remissions in both FL and MCL. Futher improvement in MCL therapy is warranted.