Medically reviewed by Dr. Brian Koffman
The Bottom Line:
The combination of tislelizumab plus zanubrutinib is effective and well-tolerated for patients with Richter’s transformation. After one year, three out of four patients were still alive, and nearly one in two were still in remission.
Who Performed the Research and Where Was it Presented:
Dr. Barbara Eichhorst from the University of Cologne and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2023.
Background:
Richter’s transformation is a rare complication where chronic lymphocytic leukemia (CLL) transforms into a much more aggressive diffuse large B cell lymphoma (DLBCL). The current standard treatment is the chemoimmunotherapy combination R-CHOP, but it doesn’t work well. Patients with Richter’s transformation who are treated with R-CHOP have a median overall survival time of only 6 to 8 months. Better therapies for Richter transformation are desperately needed.
This study tested a new combination of the BTK inhibitor zanubrutinib and the checkpoint inhibitor tislelizumab for Richter’s transformation. Checkpoint inhibitors are a class of drugs that block checkpoint proteins found on the surface of T cells and some cancer cells, allowing T cells to kill cancer cells. While checkpoint inhibitors have not been very effective for CLL thus far, they may be more useful in Richter’s transformation, which seems more sensitive to immunotherapies.
Methods and Participants:
This phase 2 clinical trial included patients with Richter’s transformation who had received up to one prior line of therapy. Patients received 12 cycles of tislelizumab plus zanubrutinib. Those with a complete response, partial response, or stable disease continued on treatment until disease progression or intolerance.
Results
- There were 58 patients enrolled in the trial, 48 of whom received at least three cycles of treatment and were included in the analysis.
- The overall response rate was 58%, with 19% of patients having a complete response and 40% having a partial response.
- After one year, 75% of patients were still alive, and 47% were still in remission.
- The most common side effects were infections (18%), diarrhea/nausea (13%), and low red or white blood cell counts (11%).
- A total of 29 patients discontinued treatment, but only three discontinued due to medication side effects. Most patients discontinued due to progressive disease.
Conclusion:
A combination of tislelizumab plus zanubrutinib is effective and well-tolerated for patients with Richter’s transformation. Having 3 out of 4 patients still alive after one year is much better than what is currently seen with R-CHOP treatment, where patients usually only have months to live. Researchers plan on testing this combination with the addition of the next-generation BCL2 inhibitor sonrotoclax to see if they can improve responses. The clinical trial is currently conducted in Germany, Denmark, and Austria. More information can be found here: Efficacy and Safety of Zanubrutinib Plus Tislelizumab Treatment With or Without Sonrotoclax for Patients With Richter Transformation (CLL-RT1).
Links and Resources:
Watch the interview on the abstract here:
You can read the ASH abstract: Tislelizumab Plus Zanubrutinib in Patients with Richter Transformation: Primary Endpoint Analysis of the Prospective, Multi-Center, Phase-II RT1 Trial of the German CLL Study Group.
Take care of yourself first.
Ann Liu, PhD
