Jaypirca Plus Venclexta With or Without Rituxan May Be Beneficial in r/r CLL

A phase 1b trial found that Jaypirca plus Venclexta, with or without Rituxan, may be a promising treatment option for patients with relapsed or refractory chronic lymphocytic leukemia.

Patients with relapsed or refractory chronic lymphocytic leukemia (r/r CLL) saw benefits from treatment with fixed-duration Jaypirca (pirtobrutinib) plus Venclexta (venetoclax; PV) and Jaypirca plus Venclexta and Rituxan (rituximab; PVR), researchers have reported.

The phase 1b BRUIN trial, findings of which were published in Blood, assigned 15 patients to treatment with PV and 10 patients to treatment with PVR for 25 cycles of 28 days each. At a data cutoff after a median time of 27 months on study for the PV arm and 23.3 months for the PVR arm, the overall response rate (patients who responded partially or completely to treatment) was 93.3% for the PV arm and 100% for the PVR arm. There were 10 complete responses (disappearance of cancer): seven in the PV arm and three in the PVR arm, researchers reported.

Eighteen-month progression-free survival (the time a patient lives without their disease spreading or worsening) rates were 92.9% in the PV arm and 80% in the PVR arm. Additionally, after 12 treatment cycles, 85.7% of patients in the PV arm and 90% of patients in the PVR arm had undetectable minimal residual disease (small amounts of cancer cells in the body following treatment).

“Both fixed-duration PV and PVR were well tolerated and demonstrated sufficiently promising efficacy to warrant further investigation in patients with R/R CLL,” researchers stated in the study.

The median age of participating patients was 66 years, most (87% in the PV arm and 70% in the PVR arm) were male and patients had received a median of two prior lines of therapy. At the time of the data cutoff, patients had spent a median of 23 months on treatment (22.8 months for the PV arm and 23 months for the PVR arm). As of the data cutoff, three patients — one in the PV arm and two in the PVR arm — were still undergoing treatment. And of the 22 patients who had discontinued treatment, nine in the PV arm and five in the PVR arm had completed all 24 cycles of combination therapy, researchers reported.

Eight patients discontinued treatment early, five in the PV arm and three in the PVR arm, due to either progressive disease, side effects and death due to a side effect unrelated to treatment, among other reasons.

Researchers further noted that there were three additional deaths, one each after discontinuing treatment for progressive disease, after discontinuing treatment for side effects and after completing 25 cycles of therapy.

According to the study, in the PV arm, the most common all-cause side effects were nausea (60%), fatigue (53%), neutropenia (low count of neutrophils, a type of white blood cell; 47%) and diarrhea (47%). Common all-cause side effects in the PVR arm were neutropenia (70%), diarrhea (60%), fatigue (50%) and nausea (40%). The most common all-cause grade 3 (severe) or higher side effect was neutropenia (47% in the PV arm and 60% in the PVR arm).

Researchers conceded that the study had important limitations, include a sample size “too small to meaningfully compare the relative tolerability and efficacy of PV and PVR regimens with each other or other treatments.”

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