Dr. Chari on Role of Immunotherapy in Myeloma

Ajai Chari, MD
Published: Monday, Feb 04, 2019



Ajai Chari, MD, associate professor, Icahn School of Medicine, Mount Sinai Health System, discusses the role of immunotherapy in the treatment of patients with myeloma.

While checkpoint inhibitors have had dramatic impact in many solid tumors and some hematologic malignancies, this class of drugs has remained questionable in myeloma. There were promising phase III studies evaluating the use of combinations of pembrolizumab (Keytruda), lenalidomide (Revlimid)/pomalidomide (Pomalyst), and dexamethasone, but these trials were abruptly halted by the FDA due to toxicity concerns. Interim results from both the KEYNOTE-183 and KEYNOTE-185 studies showed an increased risk of mortality with the addition of pembrolizumab to these regimens.

Moving forward, investigators will have to be very careful determining which immunotherapy agents will work best in which setting, Chari notes. For instance, physicians may need to tweak how checkpoint inhibitors are being used. Perhaps they should just be used in heavily treated patients with an unmet medical need who require close monitoring.

However, immunotherapy still has a role in this setting, with CAR T-cell products, such as bb2121, and immunomodulatory agents, which have shown clear benefit in some patients without the same toxicity seen with the aforementioned combinations, Chari says. Another form of immunotherapy that holds promise is in the emerging JS-K compound, he adds; this antibody-drug conjugate delivers an auristatin payload that causes cell cycle arrest and death of the cancer cell.
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Ajai Chari, MD, associate professor, Icahn School of Medicine, Mount Sinai Health System, discusses the role of immunotherapy in the treatment of patients with myeloma.

While checkpoint inhibitors have had dramatic impact in many solid tumors and some hematologic malignancies, this class of drugs has remained questionable in myeloma. There were promising phase III studies evaluating the use of combinations of pembrolizumab (Keytruda), lenalidomide (Revlimid)/pomalidomide (Pomalyst), and dexamethasone, but these trials were abruptly halted by the FDA due to toxicity concerns. Interim results from both the KEYNOTE-183 and KEYNOTE-185 studies showed an increased risk of mortality with the addition of pembrolizumab to these regimens.

Moving forward, investigators will have to be very careful determining which immunotherapy agents will work best in which setting, Chari notes. For instance, physicians may need to tweak how checkpoint inhibitors are being used. Perhaps they should just be used in heavily treated patients with an unmet medical need who require close monitoring.

However, immunotherapy still has a role in this setting, with CAR T-cell products, such as bb2121, and immunomodulatory agents, which have shown clear benefit in some patients without the same toxicity seen with the aforementioned combinations, Chari says. Another form of immunotherapy that holds promise is in the emerging JS-K compound, he adds; this antibody-drug conjugate delivers an auristatin payload that causes cell cycle arrest and death of the cancer cell.



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