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Venetoclax May Increase Toxicity But Not Efficacy When Added to R-CHOP in Double-Expressor DLBCL

July 12, 2024

Mid-July 2024

Katie Robinson

Katie Robinson is a medical writer based in New York.

In patients with previously untreated double-expressor diffuse large B-cell lymphoma (DLBCL), the addition of venetoclax to chemoimmunotherapy increased toxicity but not efficacy. This is according to results from a phase II trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This randomized trial showed that venetoclax added to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) did not improve progression-free survival (PFS) in patients with DLBCLs which co-express MYC and BCL2 (double-expressor lymphoma),” said first author Jeremy Abramson, MD, of Massachusetts General Hospital in Boston. The “addition of venetoclax did, however, substantially increase toxicities, including cytopenias and infections.”

Double-expressor DLBCL carries an unfavorable prognosis. The A051701 trial assessed the efficacy of chemoimmunotherapy with and without the addition of venetoclax, a BCL2 protein inhibitor, in patients with untreated double-expressor DLBCL. Of the 113 patients (median age = 64 years [range = 22-85]), 56 were randomized to treatment with R-CHOP (arm 1) and 57 to treatment with R-CHOP plus oral venetoclax 800 mg (arm 2) for up to six cycles (days 4-8 of cycle 1 and days 1-5 of subsequent cycles). The primary endpoint was PFS.

At a median 27-month follow-up, 84% of arm 1 and 75% of arm 2 completed the therapy per protocol. The primary endpoint was not met, with no difference in PFS observed between arm 1 and arm 2. The respective 12-month PFS estimates were 77% and 76% (hazard ratio [HR] = 0.98; 95% CI 0.48-2.01; p=0.95]. Among patients with an end-of-treatment assessment, the overall and complete response rates were 87.5% and 70%, respectively, in arm 1, and 90% and 82%, respectively, in arm 2. No difference in overall survival (OS) was observed between arm 1 and arm 2. The respective 12-month OS estimates were 94% and 79% [HR=1.27; 95% CI 0.57-2.79; p=0.56].

Grade 3 or higher adverse events (AEs) occurred more frequently with the addition of venetoclax, at 42% for arm 1 versus 76% for arm 2. The most commonly increased grade 3 or higher AEs included neutropenia at 20% and 47%; anemia at 4% and 25.5%; thrombocytopenia at 5.5% and 24%; febrile neutropenia at 7% and 16%; and fatigue at 0% and 11% for arm 1 and arm 2. No grade 5 AEs on treatment were reported with R-CHOP alone, and three were reported with R-CHOP combined with venetoclax, including lung infection, respiratory failure, and sudden death.

 “Venetoclax increased toxicity but not efficacy when combined with chemoimmunotherapy for patients with double-expressor DLBCL,” Dr. Abramson concluded.

Because the trial did not meet its primary endpoint in phase II, it did not proceed to phase III.

Any conflicts of interest declared by the authors can be found in the original abstract.

Reference

Abramson JS, Geyer SM, Pederson LD, et al. Randomized phase II/III study of R-CHOP +/- venetoclax in previously untreated MYC/BCL2 double expressor diffuse large B cell lymphoma (DLBCL): Alliance A051701. Abstract 7012. Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, June 2, 2024; Chicago, Illinois.

 

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