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CAR NK-Cell Therapy for Relapsed CLL and Other Blood Cancers

Web Exclusives — March 17, 2020

Recent results from a leading cancer center in the United States show that patients with relapsed chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) may benefit from a new type of chimeric antigen receptor (CAR) immunotherapy. Allogeneic cord blood–derived CAR natural killer (NK)-cell therapy works with the body’s immune system. CAR NK-cell therapy targets specific protein markers on cancer cells called CD19 receptors.1

The results of the first clinical trial of CAR NK-cell therapy were published in February 2020 in the New England Journal of Medicine.2 Researchers found that of the 11 patients in the study, 8 had a positive response to treatment. Of these 8 patients, 7 patients (4 with NHL and 3 with CLL) achieved a complete response. The responses to CAR NK-cell therapy occurred 1 month after infusion.2

Katy Rezvani, MD, PhD, Professor of Stem Cell Transplantation and Cellular Therapy at M.D. Anderson Cancer Center in Houston, commented on the study, saying, “We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood–derived CAR NK-cells as a potential treatment option for patients in need.”1

With other types of immunotherapy, specifically with CAR T-cell therapy, complications can include cytokine release syndrome (encompassing fever, nausea, headache, rapid heartbeat, low blood pressure, and trouble breathing) and neurotoxicity (dizziness and confusion). In the new study mentioned above, after CAR NK-cell infusion, the patients did not have any of these complications.2

Hematologic (blood-related) side effects that were seen with CAR NK-cell therapy included low platelet counts (thrombocytopenia), low white cell counts (neutropenia), and low red blood cell counts (anemia). The researchers believe that these adverse reactions are caused by chemotherapy that was given before the infusion of CAR NK-cells and not from the CAR NK-cells themselves, but this has yet to be demonstrated.2

In that study, patients who responded to CAR NK-cell treatment were able to receive other types of therapy for CLL or NHL, such as rituximab (Rituxan), lenalidomide (Revlimid), and/or stem-cell transplant. One patient who had CLL and Richter transformation (an aggressive type of lymphoma), later received venetoclax (Venclexta).2

Based on this early-phase study of CAR NK-cells, researchers look forward to starting larger clinical trials to investigate if this new therapy is safe and effective in a larger group of patients.1

References

  1. University of Texas M.D. Anderson Cancer Center news release. CD19 CAR NK-cell therapy achieves 73% response rate in patients with leukemia and lymphoma. February 5, 2020. https://bit.ly/2H17YEY. Accessed February 29, 2020.
  2. Liu E, Marin D, Banerjee P, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. New England Journal of Medicine. 2020;382:545-553.

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