Venetoclax Regimens Show Promise for CLL With Richter’s Transformation

Researchers led by Matthew S. Davids, MD, observed promising efficacy, but frequent complications, when using the venetoclax plus rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-EPOCH) regimen to treat patients with chronic lymphocytic leukemia (CLL) who experienced Richter’s syndrome, a rare transformation of CLL to aggressive lymphoma, commonly diffuse large B-cell lymphoma (DLBCL).

In a follow-up trial, they attempted to reduce toxicity using the venetoclax plus rituximab and vincristine, cyclophosphamide, doxorubicin, and prednisone (VR-CHOP) regiment.

They reported that VR-CHOP had efficacy similar to the authors’ historical efficacy with VR-EPOCH, both around a 50% rate of complete response; however, VR-CHOP demonstrated less toxicity and was also mostly used in an outpatient setting. Authors did note infections still occurred. Their findings were shown at the 17th International Conference on Malignant Lymphoma.

Swapping Venetoclax Combination Improved Outcomes

Participants received 1 cycle of R-CHOP with accelerated daily inpatient venetoclax ramp-up doses after count recovery followed by 21-day cycles of VR-CHOP with granulocyte colony-stimulating factor for a maximum of 5 cycles.

At the time of their interim report in February 2023, 27 patients with CLL and confirmed DLBCL had initiated treatment. The group had a median age of 72 years (range, 42-80 years), a median of 1 prior CLL treatment (range, 1-9 treatments), 37% had chromosome 17p13.1 deletion syndrome or TP53 mutation, and 26% had NOTCH1 mutation.

Common grade 3 hematologic toxicities included neutropenia (36%), anemia (32%), and thrombocytopenia (40%). Other grade 3 or higher toxicities included febrile neutropenia (32%) and peripheral neuropathy (12%). In 25 patients eligible for evaluation, the objective response rate was 68% (n=17), with a complete response rate of 48% (n=12).

Overall, the interim results appeared to support the authors’ hypothesis that venetoclax with a reduced-intensity chemotherapy regimen could reduce toxicity and achieve a similar response rate. “These early data support the continued exploration of VR-CHOP in this ongoing study,” the analysis concluded.

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