Richter’s transformation (a.k.a. Richter’s syndrome) is a rare complication of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), where the cancer cells transform into a much more aggressive lymphoma. It occurs in 5-10% of CLL patients, and it is associated with very rapid disease progression, limited therapeutic options, and poor survival. While chemoimmunotherapy is usually used to treat lymphomas, it isn’t very effective for Richter’s transformation. Thus, researchers have been looking into whether targeted therapies and combinations of targeted therapies might be more effective for treating Richter’s transformation.
At the American Society of Hematology (ASH) 2021, Dr. Nicole Lamanna, Associate Clinical Professor of Medicine at Columbia University Medical Center, interviewed Dr. Nitin Jain, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. They discussed early results from an ongoing study of a triple combination therapy with a PD-L1 checkpoint inhibitor for treating Richter’s transformation.
- Checkpoint proteins are found on the surface of some types of immune system cells, such as T cells and some cancer cells.
- Checkpoint proteins keep immune responses from being too strong, but they can also prevent T cells from killing cancer cells.
- Checkpoint inhibitors are a class of drugs that block checkpoint proteins allowing T cells to kill cancer cells.
- Atezolizumab is a checkpoint inhibitor that blocks PD-L1, a checkpoint protein found on cancer cells. It is already approved to treat certain types of bladder and lung cancers.
- This phase 2 clinical trial is testing the combination of:
- Venetoclax – a BCL2 inhibitor
- Obinutuzumab – a CD20 monoclonal antibody
- Atezolizumab – a PD-L1 checkpoint inhibitor
- The study is ongoing and is enrolling patients with previously untreated or relapsed/refractory Richter’s transformation.
- The current data is from 7 patients newly diagnosed with Richter’s transformation.
- All patients responded, and 6 out of 7 patients achieved a complete metabolic response, meaning that there was no sign of tumor metabolic activity as determined by PET scan.
- Three patients were able to go on to receive an allogeneic stem cell transplant.
The early data from this study are promising, and this combination would provide a non-chemotherapy option for patients with Richter’s transformation. Richter’s transformation remains one of the greatest unmet needs for CLL/SLL patients. You can find more research on Richter’s Transformation on our website here.
Please enjoy this interview with Dr. Jain from the ASH meeting, held both live and virtually in December 2021 in Atlanta, GA.
You can read the actual abstract here: Venetoclax, Obinutuzumab and Atezolizumab (PD-L1 Checkpoint Inhibitor) for Treatment for Patients with Richter Transformation.
Take care of yourself first.
Ann Liu, PhD