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Dr Chari on the Evolving Determination of Transplant Eligibility in Multiple Myeloma

Ajai Chari, MD, expands on the evolving debate surrounding transplant eligibility determination in newly diagnosed multiple myeloma.

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    "Now, with [the rise of] quadruplet therapies… [the question is:] do we need to be subjecting every patient to transplant? If we're going to have to reduce the dose of the chemotherapy for the transplant, do we really need to do [transplant], or could [a patient] do just as well with a nontransplant approach? It's a gray zone right now that we need to figure out."

    Ajai Chari, MD, director of the Multiple Myeloma Program and professor of medicine at the University of California San Francisco School of Medicine, discussed how the myeloma field is reassessing traditional criteria for transplant candidacy in light of emerging data supporting highly efficacious nontransplant approaches, as discussed at the inaugural Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma meeting.

    Chari began by addressing how the field is reassessing traditional criteria for transplant candidacy in light of emerging data supporting highly efficacious nontransplant approaches. Historically, transplant eligibility has been based on physiologic fitness rather than chronologic age, with parameters including preserved cardiac and pulmonary function, adequate performance status, and absence of major comorbidities, he stated. Importantly, renal impairment has not been an exclusion criterion, as autologous stem cell transplant (ASCT) has been successfully performed in patients receiving dialysis. Insurance coverage in the United States has extended to patients up to age 80, Chari noted. However, current therapeutic advancements—particularly the efficacy of antibody-based triplets and quadruplets—are reshaping this longstanding framework, he emphasized.

    For instance, the phase 3 MAIA trial (NCT02252172) demonstrated a 5-year progression-free survival (PFS) benefit with daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone in transplant-ineligible patients, Chari detailed. As quadruplet regimens such as daratumumab, carfilzomib, lenalidomide, and dexamethasone continue to generate robust responses, the necessity of upfront ASCT is being called into question, especially in older adults or those requiring reduced-intensity conditioning, he noted. For such patients—particularly those over age 70—the benefit-risk calculus of ASCT vs modern nontransplant therapies warrants reevaluation, Chari added.

    Ultimately, the myeloma field must move beyond rigid transplant eligibility categorizations and instead adopt a more individualized, functional approach that accounts for both disease biology and patient-specific factors, Chari stated. Future randomized trials comparing transplant and nontransplant strategies within high-performing regimens will be essential to guide practice, he concluded.


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