Immunotherapies are treatments that stimulate or suppress the immune system to help the body fight cancer. For example, monoclonal antibodies are a type of immunotherapy already commonly used to treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). They mark cancer cells to be better seen and destroyed by the immune system. Another type of immunotherapy is immune checkpoint inhibitors. These are a class of drugs that block checkpoint proteins found on the surface of T cells and some cancer cells, and in doing so, they allow T cells to kill cancer cells. A more comprehensive overview of immunotherapy can be found here.
At the annual meeting of the American Society of Hematology (ASH) 2021, Dr. Alexey Danilov, Associate Director of the Toni Stephenson Lymphoma Center at City of Hope in Duarte, CA, interviewed Dr. Alex Herrera, a hematologist-oncologist at City of Hope in Duarte, CA. They discussed new results from a phase 1 clinical trial of the atezolizumab plus immunogenic chemotherapy. Atezolizumab is a checkpoint inhibitor that blocks PD-L1, a checkpoint protein found on cancer cells. It is already approved for use in treating certain types of bladder cancers and lung cancers.
Takeaways:
- Some chemotherapies can trigger the immune response and work with the immune system to kill cancer cells. These are called immunogenic chemotherapies.
- In the lab, immunogenic chemotherapies can work synergistically with immunotherapies such as checkpoint inhibitors to improve anti-tumor responses.
- For this study, researchers recruited patients with transformed diffuse large B-cell lymphomas, including patients with Richter’s transformation.
- This was a phase 1 clinical trial, so researchers were primarily interested in determining the safety of the combination of the PD-L1 inhibitor atezolizumab plus immunogenic chemotherapy (rituximab with gemcitabine and oxaliplatin (R-GEMOX)).
- There were no unexpected toxicities. Instead, the side effects were typical of these drugs, usually seen alone.
- Common side effects included fatigue (50%), elevated liver enzymes (45%), low platelet levels (45%), nausea/vomiting (41%), diarrhea (32%), fever (32%), high blood pressure (27%), and low neutrophil levels (27%).
- 1/6 patients had dose-limiting toxicities, and two patients died from therapy
- Approximately 1 in 2 patients responded to treatment, and about 1 in 4 had a complete response.
- These are promising results given that these types of aggressive B-cell lymphomas are hard to treat.
Conclusions:
Immune checkpoint inhibitors are an evolving area in CLL. Results with checkpoint inhibitors in CLL until now have not been strong, but there are ongoing trials in the area. See our previous coverage of a phase 2 trial of atezolizumab in combination with venetoclax and obinutuzumab for CLL here. The jury is still out on how effective atezolizumab is for treating lymphomas and leukemias, and it will likely need to be used in combination with other drugs. We look forward to learning more as these clinical trials progress.
Please enjoy this interview with Dr. Herrera from the ASH meeting, held in December 2021 in Atlanta, GA, and virtually.
You can read the actual abstract here: Atezolizumab Combined with Immunogenic Salvage Chemoimmunotherapy (R-GemOx+Atezo) in Patients with Transformed Diffuse Large B-Cell Lymphoma
Take care of yourself first.
Ann Liu, PhD
