Immunochemotherapy As Induction (R-CHOP and R-HyperC-VAD/R-MA) in Mantle Cell Lymphoma, a Hungarian Multicenter Open Label Phase II Study (Rituximab [MabThera®] in Mantle Cell Lymphoma, REMENY)

Abstract

AbstractAbstract 4889 Background:Considering the especially poor outcome of mantle cell lymphoma with traditional induction chemotherapies, the Hungarian working group initiated a Hungarian Mantle Cell Lymphoma Study (REMENY) using rituximab (MabThera) based immunochemotherapy. The structure of the trial:National, multicenter, open label trial rituximab based immunochemotherapy induction in mantle cell lymphoma. Two therapies were available according to investigators' choice: R-CHOP-21 (8x) or R-HyperC-VAD/R-MA according to the MD Anderson protocol. High dose therapy + autologous stem cell support (ASCT) was allowed, according to the investigators decision.Diagnosis was based upon standard histology. Initial staging included the standard protocols, imaging techniques, bone marrow evaluation and gastrointestinal endoscopy (not compulsory at initial staging). Recruitment period was planned to be 3 years, the follow-up 2 years.Remission was evaluated according to Cheson (IWC) criteria,CR was qualified only after completion of gastroscopy and colonoscopy, which did not reveal any mantle cell related abnormality. In some cases FDG PET-CT was allowed to substitute for endoscopy.Primary endpoints: OS and PFS, safety Results:Recruitment started in June 2007 and completed unexpectedly early (Nov 2008).48 patients were included, per protocol Patients were 31 (64.58%), follow-up (24 months) was completed for 15 (31.25%) patients. Ann Arbor III-IV B 43 (89.58%) was dominant.Table 1Response to immunochemotherapyR-CHOPR-HyperC-VAD/R-MASignificanceITT N(%)36 (75%)12 (25%)ORR20 (55.6%)7 (58.3 %)p=1.000CR13 (36.1%)6 (32%)p=0.501PR7 (19.4%)1 (8.3%)p=0.659R-CHOPR-HyperC-VAD/R-MASignificancePer protocol N(%)265ORR18 (69.2%)4 (80 %)p=1.000CR11 (42.3%)4 (80%)p=0.172PR7 (26.9%)0 (0%)p=0.562Median PFS for all patients was 30.4 months (SD 5.839, 95% CI: 19–41.9). PFS median for those patients who reached a CR has not been reached while it was 23.7 months in PR (p=0.031). [Display omitted] Safety:One hundred-thirteen adverse events occurred in 31 (64.58%) patients; 53 serious adverse events in 15 (31.25%) patients: 17 cytopenia, including fever with neutropenia 7, transient bronchospasm during rituximab (MabThera) infusion 1, hyperglycemia 1 which may be treatment related. There were 20 death cases, 13 of them due to progression of disease, two due to septic complication, three heart failures and one second malignancy (breast cancer). Significantly more patients on the R-HyperC-VAD/R-MA arm experienced adverse events (11/12 patients, 91.6%) compared to R-CHOP (20/36, 55.5%, p=0.035). Conclusion:This trial further confirmed the value of adding rituximab to standard induction therapies in mantle cell lymphoma. The results are conforming to data published in literature. Higher percentage of patients completed R-CHOP regimen. R-HyperC-VAD/R-MA was more effective in inducing CR, but could be completed only in one third of patients. However, in those patients who adhered to R-HyperC-VAD/R-MA therapy, it resulted in 80% CR, vs. 42.3% in the R-CHOP group. This difference is not statistically significant (p=0.172) possibly due to low case numbers. Those patients who reached CR had significantly longer PFS. PFS obtained in this trial is comparable to international data, and could be further improved by adding immunotherapy maintenance. Planned total number of patients (48) entered the trial during the first 12 months. This was surprising, as the expected number of mantle cell lymphoma based on the international incidence data is cca. 30–35 yearly. The unexpectedly high patient numbers need further explanation. Disclosures:Off Label Use: Rituximab is not authorized for Mantle Cell Lymphoma in Hungary.