Pembrolizumab’s Potential in Treating Richter Transformation of CLL

Yucai Wang, MD, PhD, hematologist specializing in lymphoma, chronic lymphocytic leukemia (CLL), and cell therapy at Mayo Clinic, Rochester, MN, discusses the rationale, methods, and design of a study evaluating the efficacy of pembrolizumab (Keytruda) when given as both a monotherapy and in combination with B-cell receptor inhibitors for Richter transformation of CLL.

Findings from the study (NCT02332980) were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Transcription:

0:09 | This is an updated report of our phase 2 trial at Mayo Clinic. A number of years ago, we reported the initial results in the first cohort of Richters patients. At that time, we had 9 patients with Richters treated with single-agent pembrolizumab. We saw encouraging preliminary efficacy with 4 out of the 9 patients responding. Later on, we enrolled more patients in this trial, the so-called expansion cohort of Richter’s. We also amended the protocol to allow the addition of a BTK inhibitor or PI3K inhibitor in patients who progress on single-agent pembrolizumab. This report is going to summarize both the efficacy of single-agent pembrolizumab in this expanded cohort, and also report the efficacy of the combination therapy phase for those patients who progressed on single-agent, and then receive doublet therapy.

1:16 | For the single-agent phase, basically, to come to this trial, one has to have pathology confirmed Richter's transformation, which is defined as aggressive lymphoma derived from previous or current CLL. We do not require any prior treatment history for Richters specifically to be eligible. In other words, they could have received all kinds of therapy for CLL or Richter’s previously, or they could have just been newly diagnosed with the disease and have never received treatment yet.

1:55 | Once they are enrolled, if they fulfill the eligibility criteria of the trial, they will be first treated with single-agent pembrolizumab every 3 weeks, a standard dosing for this drug. If they have only stable disease after 3 cycles, they are allowed to add on a BTK inhibitor or PI3K inhibitor. If they respond great, but after they relapse, they can enter the combination therapy phase as well by adding a BTK or PI3K inhibitor. Patients who do not respond to single-agent pembrolizumab, they are allowed for sure to add a BTK or Pl3K inhibitor. In terms of efficacy evaluation, we are first going to look at the single-agent phase. And for patients who added all my BTK inhibitors or PI3K inhibitors, we will look at the response for the doublet therapy phase from that new start as well.