Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM )retired), MSEd
The Bottom Line:
Though it is still early, the combination of pirtobrutinib–venetoclax–obinutuzumab appears to have good efficacy in patients with Richter transformation.
Who Performed the Research and Where Was it Presented:
Dr. Nitin Jain from The University of Texas MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Richter transformation is a rare transformation of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) into a fast-growing, aggressive lymphoma, usually DLBCL (diffuse large B-cell lymphoma). While Richter transformation is traditionally treated with chemotherapy regimens such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), patient outcomes are poor, with most patients living less than one year after diagnosis. New therapies are greatly needed, and researchers have been testing different combination therapies for Richter transformation. In this study, researchers looked at the efficacy of a combination of noncovalent BTK inhibitor pirtobrutinib, BCL2 inhibitor venetoclax, and anti-CD20 monoclonal antibody obinutuzumab for patients with Richter transformation.
Methods and Participants:
This was part of a larger phase 2 clinical trial testing the efficacy of pirtobrutinib-venetoclax-obinutuzumab in patients with CLL or Richter transformation. Eligible patients for this portion had previously untreated or relapsed / refractory Richter transformation arising from CLL. Obinutuzumab was given for six months. Pirtobrutinib and venetoclax were given for two years.
Results:
- Twelve patients have enrolled in the study thus far, with a median age of 70 years.
- Three patients had not been previously treated for Richter transformation.
- With 15 months of follow-up, 8 out of 12 patients (67%) responded to treatment.
- Seven patients had a complete metabolic response, and one patient had a partial metabolic response as measured by PET scan.
- Three patients did not respond to treatment, and one patient had stable disease.
- Among the eight responding patients, one patient went on to receive an allogeneic stem cell transplant.
- Six out of the seven patients who continued on treatment reached undetectable measurable residual disease in the bone marrow by month 7.
- At 12 months, the event-free survival (number of patients without disease progression, discontinuation of treatment, or death) was 73%, and the overall survival (number of patients alive) was 83%.
- There were four patient deaths, including three patients who did not respond to treatment and one patient who was in remission but died from complications related to an allogeneic stem cell transplant.
Conclusions:
Though this data is still early, pirtobrutinib-venetoclax-obinutuzumab appears to have good efficacy in patients with Richter transformation. Patients will need to be followed longer to determine the durability of these responses, and the study is still recruiting more patients. Interestingly, though, these responses appear to be deeper and more durable than those seen with the combination of ibrutinib-venetoclax-obinutuzumab in a similar small study. If successful, pirtobrutinib-venetoclax-obinutuzumab could provide patients with Richter transformation with a non-chemotherapy treatment option.
If you are interested in participating in this study, more information can be found here:
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Pirtobrutinib, venetoclax, and obinutuzumab for patients with Richter transformation: A phase 2 trial
