Pirtobrutinib Regimen May Offer Prolonged Remissions in Pretreated CLL

A triplet consisting of pirtobrutinib (Jaypirca), venetoclax (Venclexta), and rituximab (Rituxan; PVR) significantly improved progression-free survival vs VR alone among patients with previously treated chronic lymphocytic leukemia (CLL), according to data from the phase 3 BRUIN CLL-322 trial (NCT04965493) presented at the European Hematology Association (EHA) 2026 Congress.

In a conversation with CancerNetwork^® at the meeting, study investigator Matthew S. Davids, MD, MMSc, discussed what the depth of response observed with the PVR triplet may represent about the prospect of prolonged treatment-free intervals among patients with previously treated disease. Although the minimal residual disease (MRD) data were still evolving at the time of analysis, Davids noted high rates of undetectable MRD with the triplet among patients with evaluable samples. These findings, he said, may suggest a “good” likelihood of prolonged remissions and a possibility for long treatment-free intervals, even among those with high-risk features.

Davids is chief of the Division of Lymphoma and associate director of the CLL Center at Dana-Farber Cancer Institute, as well as an associate professor of Medicine at Harvard Medical School.

Transcript:

As we think about depth of response in CLL, there are a couple of parameters: the rate of complete remission, and then the rate of undetectable MRD. In this study, the PVR regimen was superior in both respects, so a higher CR rate and a higher rate of undetectable MRD compared to VR. I would say that, right now, the MRD data are still in evolution for this study. There's still a lot of patients with pending samples; they haven't necessarily reached the end of treatment time point yet, or they have reached that time point, but the sample hasn't been run.

When we look at the evaluable patients who have samples, we see about a 25% improvement in terms of the depth of response at a level of 10^–4, and that holds up. We use the clonoSEQ assay, so we can look at 10^–5 and 10^–6, and even at that deep level, we see very high rates of undetectable MRD with PVR. To me, this suggests very good likelihood that we'll see prolonged remissions, especially in those [patients who received] PVR, and gives me good confidence that we can use that regimen and expect a very long treatment-free interval, even in patients who have high-risk CLL.

Reference

Davids M, Eyre TA, Woyach J, et al. Fixed-duration pirtobrutinib plus venetoclax–rituximab versus venetoclax–rituximab for patients with previously treated CLL/SLL: a phase 3, randomized trial (BRUIN CLL-322). Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract LB5001.