Phase II Single-Arm “Window-of-Opportunity” Study of a Combination of Obinutuzumab and Venetoclax in Early Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) - First Results of the AGMT NHL15B Study

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.26-26
• Main Authors: Jaeger, Ulrich, Egle, Alexander, Simonitsch-Klupp, Ingrid, Heibl, Sonja, Neumeister, Peter, Willenbacher, Ella, Erlsbacher, Florian, Larcher-Senn, Julian, Fridrik, Michael A., Greil, Richard
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-136953

Background: Patients with diffuse large B-cell lymphoma (DLBCL) relapsing early (within 12 months) or primary refractory to induction therapy with rituximab (R) and CHOP have a poor prognosis with a median overall survival (OS) of less than 2 years. Relapse immuno-chemotherapy followed by autologous stem cell transplantation is the standard of care, but response rates are still not satisfactory and a substantial number of patients are ineligible for transplant or aggressive therapies. Novel antibodies, small molecules and CAR-T cell therapies have been explored for this population. We initiated a study with obinutuzumab and venetoclax to evaluate the effect of a chemo-free regimen in these refractory or early relapsing DLBCL patients with the option to prepare these patients for cell therapy. Study design and Methods: Twenty-one patients with DLBCL (relapsed within 12 months or primary refractory), detectable Bcl-2 protein expression and CD20 positivity were included in this prospective, Fleming-design Phase II single-arm study. Obinutuzumab was given i.v. at a dose of 1000 mg on days 1, 8, 15 in cycle 1 and on day 1 of each following 21-day cycles. Venetoclax was given at 800mg daily p.o. Treatment was repeated for up to 3 cycles. Eligible patients were planned to either proceed to stem cell transplantation or receive up to 9 cycles of maintenance if ineligible for transplant. The primary endpoint was objective response rate by Lugano 2014 criteria after 3 cycles (investigator assessed). Secondary objectives included dose-limiting toxicities, response duration, progression-free and overall survival and ability to proceed to further stem cell transplantation. A biomarker program investigated histopathologic, genomic and biological factors associated with outcome. The trial was registered under Eudract Nr. 2016-001760-10 andNCT02987400. Results: The ITT population consisted of 21 patients (median age 64 years, 9 M, 12F) with refractory or early relapsed DLBCL after 1 (N=11) to 4 previous lines of therapy. The majority of patients received 3 cycles of obinutuzumab-venetoclax (range 1-8). The regimen was well tolerated. No DLTs were observed. Adverse events were observed in 85.7% with gastrointestinal disorders and administration site conditions being most prominent. Cytopenias were reported in 23.8% and infections in 19%. Severe adverse events were observed in 19%. The objective response rate was 38.1% (8/21 patients) with a best response of 5 CR (23.8%) and