PF306 A PHASE 2 STUDY OF OFATUMUMAB IN COMBINATION WITH HYPER‐CVAD/MA IN PATIENTS WITH NEWLY DIAGNOSED MANTLE CELL LYMPHOMA

Background: The outcomes of mantle cell lymphoma (MCL) remain suboptimal despite aggressive upfront chemoimmunotherapy, consolidation with high dose chemotherapy followed by autologous stem cell transplant (HDC‐ASCT) and rituximab maintenance. Attaining complete remission (CR), especially when confirmed by high sensitivity flowcytometry has been associated with sustained remissions beyond 5 years, suggesting that a flow‐CR may be used as a surrogate for long term survival. Rituximab‐based therapy results in a flow‐CR rate of 48%. Pre‐clinical studies have demonstrated that ofatumumab (O) is more active than rituximab in eliciting complement‐mediated cytotoxicity (CMC) in MCL cell lines, primary tumor cells and murine xenograft model. Aims: We evaluated the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O‐HyperCVAD) in newly diagnosed MCL (NCT01527149). Methods: his was an open‐label, prospective phase 2 study. Thirty‐seven transplant‐eligible patients with newly diagnosed MCL were enrolled at 2 sites. Ofatumumab 1000 mg was given every 3 weeks on day 1, followed by standard doses of alternating HyperCVAD and MA starting on day 3. A total of 6 cycles was planned, followed by HDC‐ASCT. Primary objectives were to determine the overall response rate (ORR) and CR rate (CRR) at the end of therapy. Secondary objectives included flow‐CR rate, progression free survival (PFS), overall survival (OS), feasibility of successful mobilization of autologous stem cells and safety assessment. Exploratory endpoints included correlation of minimal residual disease (MRD) with survival, correlation of surface CD20 levels with response and to compare differences in RR according to Cheson and modified Cheson (MC) criteria. Results: Median age was 58 yrs; 73% were males, 91% has ECOG PS 0–1, majority (81%) had stage 4 disease with 85% having bone marrow involvement; 22% had low risk, 42% had intermediate risk and 36% had high risk MIPI score. 86% patients underwent HDC‐ASCT. Of patients who underwent collection, all except one collected adequate stem cells. The ORR and CRR were 95% and 62% by Cheson and 92% and 78% respectively by modified Cheson criteria. The median PFS and OS were 46 months and 56 months respectively. Patients who attained CR had a longer PFS and OS; none of the other baseline patient and disease characteristics correlated with outcomes. Flow‐CR data and exploratory endpoints are under analysis and will be reported at the meeting. There were 3 deaths while on therapy‐ 2 from sepsis and one from leukemia. 22% patients had grade 3 and 68% had grade 4 adverse events, majority were hematological adverse events from HyperCVAD/MA. Ofatumumab‐related infusion reactions were noted in 78% patients, of which 11% were grade 3, rest were grade 2. Summary/Conclusion: The addition of ofatumumab to HyperCVAD/MA is well tolerated and yields high response rates in patients with newly diagnosed mantle cell lymphoma. Despite higher ORR and CR rates, survival outcomes are similar to historical cohorts using rituximab‐HypeCVAD/MA.