Medically reviewed by Dr. Brian Koffman
The Bottom Line:
Pirtobrutinib is a useful treatment option to temporarily manage Richter’s transformation, but long-term treatments are still needed.
Who Performed the Research and Where Was it Presented:
Dr. William Wierda from MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2023.
Background:
The FDA recently approved pirtobrutinib as a treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). It is an effective reversible (noncovalent) BTK inhibitor even in patients who have developed resistance to irreversible (covalent) BTK inhibitors such as ibrutinib, acalabrutinib, or zanubrutinib. Richter’s transformation is a rare complication of CLL / SLL, where the cancer turns into an aggressive lymphoma. It has an extremely poor prognosis, and available therapies do not provide durable remissions. The BRUIN study is a clinical trial of pirtobrutinib, which enrolled patients with Richter’s transformation. In this interview, Dr. Wierda provides updated results on how patients with Richter’s transformation are doing on pirtobrutinib therapy.
Methods and Participants:
The BRUIN study is a phase 1/2 clinical trial testing pirtobrutinib in patients with previously treated B-cell malignancies, including those with CLL and Richter’s transformation. It included patients with both untreated and previously treated Richter’s transformation. In total, 82 patients with Richter’s transformation have been treated in this study.
Results:
- Most patients had received prior treatment for their CLL and Richter’s transformation, with a median of four prior lines of therapy.
- Half of patients (50%) responded to pirtobrutinib therapy, and 13% had a complete response.
- The median duration of response was 7.4 months, and the median time on treatment for patients who responded was 8.3 months.
- The median overall survival was 12.5 months.
- Eight patients stopped pirtobrutinib to pursue curative-intent therapy (allogeneic stem cell transplant).
- Pirtobrutinib was well-tolerated with limited side effects.
- The most common side effects were low white blood cell count (29%), fatigue (24%), diarrhea (18%), low platelet count (18%), shortness of breath (18%), and fever (18%).
- Cardiac side effects such as hypertension (4%) and atrial fibrillation (abnormal heart rhythm, 1%) were infrequent.
- No patients discontinued pirtobrutinib due to a treatment-related side effect.
Conclusions:
Pirtobrutinib is a useful treatment option to temporarily manage Richter’s transformation, particularly as a “bridge therapy” to something potentially curative, such as an allogeneic stem cell transplant. Still, by itself, it is only a temporary measure. Long-term treatments are still needed. It may also be useful as part of combination treatments, but this remains to be tested in clinical trials.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Pirtobrutinib in Richter Transformation: Updated Efficacy and Safety Results with 18-Month Median Survival Follow-up from the Phase 1/2 BRUIN Study
Take care of yourself first.
Ann Liu, PhD
