New study suggests kinase addition can enhance Pembrolizumab for CLL treatment

Addition of BCR Kinase Inhibitor to Pembrolizumab Increases Treatment Efficacy in CLL with Richter Transformation

Overview

According to updated results of an interventional trial, found in the Journal of Clinical Oncology, adding a BCR kinase inhibitor (such as ibrutinib or idelalisib) to the monoclonal antibody pembrolizumab, increases treatment efficacy in patients whose chronic lymphocytic leukemia (CLL) has undergone Richter transformation (RT).

Study Details

The research team enrolled 26 patients with RT (9 in the initial group and 17 in the expansion group) at two Mayo Clinic sites in Minnesota and Arizona. The participants’ median age was 68.5 years, and 38% (10) had the del(17p) or the TP53 mutation. They had received between 1 and 10 prior lines of therapy, with a median of 3 lines; 58% (15) of patients had previously received ibrutinib, and among those, 14 had progressive disease while on ibrutinib. Participants received pembrolizumab monotherapy (200 mg IV Q3W) for up to 12 months. Those with stable disease (SD) after 3 months of pembrolizumab or with progressive disease (PD) at any time during monotherapy were given the option to enter the combination therapy phase by adding a B-cell receptor (BCR) kinase inhibitor to pembrolizumab.

Results

The combination therapy with pembrolizumab and a BCR kinase inhibitor is associated with an increased efficacy (overall response rate, >60%), similar to other reports, as noted in the abstract of the presentation at the 2024 ASCO Annual Meeting. The researchers investigated participants’ overall response rate, progression-free survival, and overall survival. The results support further investigation of immune checkpoint inhibitor-based combination therapy in RT. BCR kinase inhibitors are already known to be effective in patients with CLL, and this study shows that by combining them with immunotherapy, we can improve outcomes for patients with RT who have limited treatment options.

Managing Richter Transformation (RT)

Effectively managing Richter transformation (RT) — the development of aggressive large-cell lymphoma in the setting of underlying CLL or small lymphocytic lymphoma (SLL) — is a major clinical challenge. This study updates data from a phase II clinical trial that shows modest efficacy of pembrolizumab monotherapy in patients with RT, including findings from an expansion cohort and a combination therapy cohort.

Conclusion

This study highlights the importance of combining therapies for patients with CLL who have undergone Richter transformation (RT). The combination therapy with pembrolizumab and a BCR kinase inhibitor is associated with an increased efficacy, justifying further investigation of immune checkpoint inhibitor-based combination therapy in RT.

Long-Tail Keywords

What is Richter transformation?
How effective is pembrolizumab monotherapy in Richter transformation?
What is the role of BCR kinase inhibitors in CLL?
What are the benefits of combining immunotherapy with BCR kinase inhibitors?
What are the current challenges in treating Richter transformation?

Originally Post From https://www.physiciansweekly.com/adding-a-kinase-to-pembrolizumab-may-increase-cll-treatment-efficacy/