Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
In an early-stage clinical trial, half of the patients with relapsed / refractory Richter transformation responded to treatment with BTK degrader BGB-16673.
Who Performed the Research and Where Was it Presented:
Dr. Meghan Thompson from Memorial Sloan Kettering Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Bruton tyrosine kinase (BTK) degraders are a new class of drugs being developed for the treatment of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). BTK inhibitors work by directly binding to the BTK protein (reversibly or irreversibly) and inhibiting its function. However, over time, resistance mutations can develop that prevent BTK inhibitors from binding to BTK, rendering them ineffective. BTK degraders, on the other hand, work by causing the breakdown of the BTK protein so that it is destroyed. BGB-16673 is an experimental BTK degrader that has shown potential for treating relapsed / refractory CLL. Here, researchers evaluated its safety and efficacy in patients with Richter transformation, a rare, hard-to-treat aggressive complication of CLL / SLL.
Methods and Participants:
This study was part of a larger phase 1/2 clinical trial evaluating the safety and efficacy of BGB-16673 in patients with B-cell cancers. This study included patients with relapsed / refractory Richter transformation.
Results:
- Thus far, 24 patients with Richter transformation have been treated with BGB-16673 at four different dose levels (100, 200, 350, or 500 mg).
- Patients had received a median of two prior therapies for Richter transformation, and all patients had previously been treated with chemoimmunotherapy.
- High-risk features were common in this group of patients, including TP53 mutation (83%), unmutated IGHV (91%), and PLCG2 mutation (24%).
- 19% of patients had BTK mutations at baseline.
- Median follow-up was five months.
- The overall response rate (how many people had their cancer shrink) was 52%.
- The complete response rate (how many people had their blood counts and lymph nodes return to normal) was 10%.
- Of the 11 patients who responded to treatment, five maintained their response for over six months.
- The median time to first response was three months.
- One patient was able to discontinue treatment to undergo an allogeneic stem cell transplant.
- Common side effects included low white blood cell counts (38%), nausea (21%), diarrhea (17%), swelling from fluid retention (17%), and pneumonia (17%).
- Two patients had their doses reduced due to side effects, and one patient died from a fever related to progressive disease.
Conclusions:
In this early-stage clinical trial, half of the patients with relapsed / refractory Richter transformation responded to treatment with BTK degrader BGB-16673, which is very promising for a well-tolerated monotherapy. While the responses were not as good as those seen in patients with relapsed / refractory CLL, this is not surprising since Richter transformation, especially when it’s relapsed / refractory, is much more aggressive and difficult to treat than CLL. BTK degrader therapy could be useful to some patients with Richter transformation, and a subset of patients did have responses that lasted over six months. It could also potentially be combined with other therapies to try to improve efficacy. New therapies are desperately needed for richer transformation, and BGB-16673 could potentially be another tool in the toolbox.
Links and Resources:
You can read the actual ASH abstract here: Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed/refractory Richter transformation: Results from the ongoing phase 1 CaDAnCe-101 study
Take care of yourself first.
Ann Liu, PhD
