1. Holt, Chuck

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New treatments for patients with multiple myeloma were a popular topic at the National Comprehensive Cancer Network 2022 Annual Congress: Hematologic Malignancies.

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During this event, Noopur S. Raje, MD, shared some of her vast expertise on the topic in a presentation titled "Managing Newly Diagnosed Multiple Myeloma." She is Professor of Medicine at Harvard Medical School and Director of the Multiple Myeloma Program in Medical Oncology at Massachusetts General Hospital Cancer Center.


Joining Raje during the conference session, titled "Treatment Options for Multiple Myeloma," was Shaji K. Kumar, MD, consultant in the Division of Hematology and Professor in the College of Medicine at the Mayo Clinic in Rochester, Minn. During the conference, Kumar delivered his presentation, "Strategies for Treating Relapses in Multiple Myeloma."


Following their respective presentations, the pair hosted a Q&A with live and virtual attendees. In her presentation, Raje reviewed treatment options for multiple myeloma and also discussed diagnoses based on risk assessment. This included clinical data that supports newer treatment options, including immunotherapies, minimal residual disease (MRD) testing, and how physicians can make the treatment selection process more individualized for patients with multiple myeloma.


"When treating patients with multiple myeloma, the goal is to achieve MRD-negative disease," Raje said. "We want to obtain a deep response. And the good news is that we can actually get to MRD-negative disease."


There are several clinical trials of interest, according to Raje. For transplant-eligible patients with multiple myeloma, she pointed to the Phase III PERSEUS study, which is trialing daratumumab, and also the Phase III GMMG-HD7 study evaluating a combination of isatuximab and lenalidomide.


For transplant-ineligible patients, Raje gave a nod to Phase III studies CEPHEUS (evaluating daratumumab) and IMROZ (isatuximab), and SWOG S2209, which is testing new drug combinations for patients with myeloma who are considered too frail for a stem cell transplant. Raje is also excited about CARS/BiTES/Dual targeting strategies in the upfront setting for patients with multiple myeloma.


The standard of care for patients with multiple myeloma, meanwhile, remains transplant followed by maintenance. Most cancer physicians, however, treat patients with multiple myeloma using a triplet of drug therapies. A typical triplet therapy includes a corticosteroid, such as dexamethasone and prednisone; an immunomodulatory like lenalidomide, pomalidomide, thalidomide; and a proteasome inhibitor, such as bortezomib, carfilzomib, and ixazomib.


Raje typically prescribes a triplet of therapy that includes lenalidomide, bortezomib, and dexamethasone (RVd); carfilzomib, lenalidomide, and dexamethasone (KRd); and bortezomib, cyclophosphamide, and dexamethasone (VCd).


"And now quadruplets are being used due to the availability of immunotherapies," Raje noted. "How we can incorporate these immune strategies into the upfront setting will be quite exciting in the near future. The power of immunotherapies has yet to be harnessed."


Continuous therapy has for many years been the accepted treatment regime for multiple myeloma, although Raje believes it may be time to ask why. "I do think that now that we have tools, such as MRD, we can at least begin to ask the question of de-escalation of treatment," she stated.


Raje anticipates more novel agents for treating multiple myeloma will be brought to the upfront setting soon, particularly treatment strategies that have worked well in the relapsed/refractory setting.


"The concept of fixed duration using MRD is something we are all interested in studying," she said. "Having a tool such as MRD will allow us to see in which patients we can actually stop treatment or deescalate."


Multiple Myeloma in R/R Setting

In his presentation, Kumar focused on new treatment strategies for patients with relapsed/refractory multiple myeloma, including several immunotherapies, CAR T-cell therapy, and bispecific T-cell engagers, which are antibodies "that enable T cells to get closer to a myeloma cell and kill it," he said.


Physicians can determine the best strategy for treating patients with multiple myeloma, Kumar said, by deciding upon the best "package of drugs available at a given time, using optimal combinations of therapeutics in the best sequence and switching to regimens with new drug classes that offer the best outcomes.


"I think the most important thing," Kumar said, "is what drugs they have been exposed to and how well they tolerated it, what kind of response did they get, and are they refractory to that drug?" Kumar said.


Also high on Kumar's list of characteristics physicians need to consider when treating patients with relapsed/refractory multiple myeloma include patients at high risk versus standard risk; age, fragility, and comorbidity; toxicity with prior drugs; transplant eligibility and outcomes; patient preferences; goals for care; and the logistics of drug administration.


Taking these characteristics into consideration can help physicians develop a more personalized plan of care for patients with relapsed/refractory multiple myeloma, said Kumar, who concluded, "The future of [multiple myeloma] treatment strategies will be in developing more individualized approaches."


Chuck Holt is a contributing writer.