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EHA 2021: Dr. Anthony Mato on pirtobrutinib (LOXO-305) for Richter’s transformation in chronic lymphocytic leukemia (CLL)

Richter’s transformation (a.k.a. Richter’s syndrome) is a rare complication of chronic lymphocytic leukemia (CLL) where the cancer cells transform into a much more aggressive lymphoma. It occurs in 2-10% of CLL patients, and it is associated with very rapid disease progression, limited therapeutic options, and poor survival. Outcomes have generally been poor because the lymphoma does not respond well to traditional treatments. While chemotherapy is often used to treat Richter’s transformation, it is not very effective.  

At the annual meeting of the European Hematology Association (EHA) 2021, our own Dr. Brian Koffman interviewed Dr. Anthony Mato, Director of the CLL Program at Memorial Sloan Kettering Cancer Center. They discussed preliminary results from a clinical trial of pirtobrutinib (formerly LOXO-305) in a subset of patients with Richter’s transformation. 

Takeaways: 

  • This is a phase 1/2 clinical trial of pirtobrutinib, which is a highly-selective, reversible (non-covalent) Bruton’s tyrosine kinase (BTK) inhibitor we have previously discussed here. 
  • The trial is currently ongoing, and this portion of the trial is enrolling patients with previously treated Richter’s syndrome. 
  • Thus far, 17 patients with Richter’s transformation have been enrolled in the trial.  
  • These patients have already been heavily treated. The median number of prior therapies for CLL was 6, and the median number of prior therapies specifically for Richter’s transformation was 2. 
  • Thus far, 15 patients have had a response assessment, and 67% (2 out of 3) responded to treatment. 
  • Though it is still early on, some patients have continued to respond after 6+ months of follow-up. 
  • Pirtobrutinib is probably not a cure for Richter’s transformation, but it may help stabilize the disease, improve quality of life, and potentially serve as a bridge to other therapies such as CAR-T therapy or stem cell transplant. 
  • Thus far, pirtobrutinib has been well-tolerated with very few serious adverse events. 

Conclusions: 

There is a large unmet need for effective treatments for Richter’s transformation. Even though these results are only in a small number of patients with a short follow-up period, pirtobrutinib seems like a promising candidate thus far. This is encouraging news for patients who have few options, and we hope that we continue to see positive results with longer term follow up in more patients. If you are interested in participating, the trial is still ongoing at multiple sites in the United States and worldwide. More information can be found here. 

Please enjoy this brief interview with Dr. Mato from the virtual EHA meeting which was held June 2021. 

You can read the actual abstract here: Pirtobrutinib (LOXO-305), a next generation, highly-selective, non-covalent BTK inhibitor in previously treated Richter transformation: results from the phase 1/2 BRUIN study 

Take care of yourself first. 

Ann Liu, PhD