Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation.

BACKGROUND: More than one-half of high-risk patients with relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) relapse after autologous hematopoietic cell transplantation (auto-HCT). In this phase II study, we investigate the long-term outcomes of high-risk patients with rrDLBCL receiving intensive consolidation therapy (ICT) with OVA (ofatumumab, etoposide, and high-dose cytarabine) prior to auto-HCT. PATIENTS AND METHODS: The primary endpoints were the ability of OVA to mobilize peripheral stem cells and the 2-year progression-free survival (PFS) rate following OVA. Secondary endpoints included safety, 2-year overall survival (OS), impact of cell of origin (COO), and the prognostic utility of next-generation sequencing minimal residual disease (MRD) testing. We simultaneously retrospectively assessed the outcomes of DLBCL patients who underwent ICT with a similar regimen at our institution. RESULTS: Twenty-seven patients received salvage chemotherapy, with a response rate of 25% in patients with germinal center B-cell (GCB)-DLBCL versus 92% in patients with non-GCB-DLBCL (P = .003). Nineteen responding patients underwent ICT with OVA (100% successful stem cell mobilization). The 2-year PFS and OS rate was 47% and 59%, respectively, with no difference based on COO. Similar findings were observed when the study and retrospective cohorts were combined. Neutropenia was the most common toxicity (47%). MRD-negative patients at the completion of salvage had a median OS of not reached versus 3.5 months in MRD-positive patients (P = .02). CONCLUSIONS: OVA followed by auto-HCT is effective and safe for high-risk rrDLBCL. Patients with GCB-DLBCL had a lower response to salvage chemotherapy, but no difference in outcomes based on COO was seen after auto-HCT. MRD testing in the relapsed setting was predictive of long-term survival.

Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial.

INTRODUCTION: We designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination. PATIENTS AND METHODS: The protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3. RESULTS: Ten patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m2, and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months. CONCLUSION: Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options.