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NCCN 2023: Update on Managing Resistant Myeloma

By: JNCCN 360 Staff
Posted: Wednesday, April 5, 2023

At the recent NCCN 2023 Annual Conference in Orlando, Florida, Natalie S. Callander, MD, of the University of Wisconsin School of Medicine, Carbone Cancer Center, Madison, explored the ever-evolving treatment landscape in relapsed or refractory multiple myeloma. The degree of treatment resistance is a key factor in the treatment strategy of those with relapsed disease.

In the setting of first relapsed, Dr. Callander indicated that anti-CD38 antibody–based combination therapy would be preferred unless patients have already received these agents. In that case, she noted, carfilzomib may be an alternative option. Various triplet regimens have been supported by phase III clinical trial data, such as daratumumab plus lenalidomide and dexamethasone or isatuximab plus carfilzomib and dexamethasone. “There are data showing that if you treat a patient with an antibody at first relapse, you’re not ruining them for a response later on,” commented Dr. Callander.

In the setting of late relapse, most patients will become “triple-class–refractory” to an immunomodulatory drug, proteasome inhibitor, and antibody. Treatment beyond the third line may include bispecific antibodies as well as chimeric antigen receptor (CAR) T-cell therapy. “A lot of us like selinexor in combination with carfilzomib for later-line therapy,” she added. Other agents she briefly discussed included antibody-drug conjugates, CAR T-cell therapies, bispecific T-cell engagers, and naked antibodies. In addition, she mentioned some of the other novel agents on the horizon, including iberdomide and mezigdomide (oral cereblon E3 ligase modulators) and the first-in-class immunocytokine modakafusp. In addition, Dr. Callander predicted that immunotherapy “is where myeloma is going in the next few years, in a big way.”

Disclosure: Dr. Callander reported no conflicts of interest.


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