Please share your name, title, and a brief overview of your professional history.

Ben Derman, MD: My name is Ben Derman, MD, and I am director of the Multiple Myeloma Program at the University of Chicago.

I am an academic clinical investigator specializing in the treatment of plasma cell disorders, with research spanning several key areas. My primary focus is the use of measurable (minimal) residual disease (MRD) in multiple myeloma. My work aims to advance methods for detecting residual disease, including improving bone marrow-based assays and developing peripheral blood-based approaches that may complement or replace bone marrow testing.

I also study how MRD can guide clinical decision-making and identify patients who may achieve durable treatment-free remission. This work led to the design, execution, and publication of the MRD2STOP trial, which evaluates treatment discontinuation in patients with sustained MRD negativity. The study has contributed to a changing treatment paradigm by providing evidence supporting MRD-guided discontinuation of therapy.

In addition, I investigate novel immunotherapeutic strategies, including new applications of chimeric antigen receptor (CAR) T-cell therapy and T-cell engagers in multiple myeloma. I served as a member of the International Myeloma Working Group that developed guidelines for the use of these therapies. My experience with CAR T-cell therapy has also informed studies evaluating delayed neurotoxicity and enterocolitis following cilta-cel (Carvykti) treatment. In addition, I have served as site principal investigator for clinical trials evaluating T-cell engagers, including novel trispecific antibodies.

The updated ASCO Living Guideline recommends broader use of CD38-targeted quadruplet regimens in both transplant-eligible and many transplant-ineligible patients. How do you expect these recommendations to influence payer coverage policies, clinical pathways, and treatment access?

Dr Derman: With randomized phase 3 evidence demonstrating the superiority of quadruplet therapy for patients with newly diagnosed multiple myeloma, regardless of transplant eligibility, it was important for the guideline to emphasize that patients with adequate fitness should receive quadruplet induction therapy.

In many ways, these recommendations should accelerate changes that are already occurring in clinical practice. From a payer perspective, endorsement by the ASCO Living Guideline should promote more consistent coverage and reduce the need for case-by-case appeals.

Access may remain more variable among transplant-ineligible patients, however, because this population is heterogeneous and not every patient requires or can tolerate quadruplet therapy. Payers may seek documentation of performance status, frailty, or the clinical rationale for selecting a quadruplet regimen over a less intensive alternative.

From a clinical pathways perspective, I would like to see the field move beyond the traditional transplant-eligible versus transplant-ineligible framework. Instead, we should think about patients who are eligible for quadruplet therapy and those who are not. This approach better distinguishes older but fit patients who may benefit from quadruplet therapy from more frail or vulnerable patients for whom adding a fourth agent may not be appropriate.

Although the guideline cannot, by itself, guarantee equitable access, its recommendations establish an aspirational standard that clinicians, health systems, and payers should strive to achieve.

At the same time, quadruplet regimens increase treatment complexity, infusion and injection visits, monitoring requirements, supportive care needs, and overall costs. These burdens may disproportionately affect patients treated in community settings, those who live far from treatment centers, and those with limited transportation or caregiver support.

The guideline emphasizes more individualized treatment decisions based on factors such as frailty, transplant eligibility, measurable residual disease (MRD), prior therapies, and patient preferences. How can managed care organizations support personalized care while maintaining evidence-based, cost-effective coverage policies?

Dr Derman: Managed care organizations can support personalized care by designing coverage policies that are evidence-based yet flexible enough to account for clinically meaningful differences among patients. Rather than relying on one-size-fits-all pathways, policies should allow clinicians to incorporate frailty, comorbid conditions, transplant eligibility, disease risk, prior therapies, and MRD when selecting treatment.

Managed care organizations can also promote cost-effective care by supporting shared decision-making, appropriate dose and schedule modifications, the use of lower-intensity regimens for frail patients, and—perhaps most importantly—treatment discontinuation or de-escalation strategies when supported by emerging evidence.

There is growing interest in moving away from the longstanding paradigm of indefinite therapy toward time-limited treatment for appropriately selected patients. This approach may be particularly relevant for patients with sustained MRD negativity and no evidence of disease on advanced imaging. Because these assessments often need to be repeated over time to establish sustained disease control, coverage for serial MRD testing and appropriate imaging could ultimately enable more informed treatment de-escalation while reducing unnecessary treatment exposure and health care costs.

At present, however, the ASCO Living Guideline does not recommend using MRD routinely to direct treatment decisions. Managed care organizations should therefore support access to MRD testing when clinically appropriate while avoiding policies that require MRD as an inflexible criterion for treatment continuation, escalation, or discontinuation before the supporting evidence is sufficiently mature.

With CAR T-cell therapies and bispecific antibodies moving earlier in the treatment paradigm for relapsed multiple myeloma, what are the biggest challenges payers face in balancing timely patient access with affordability and appropriate utilization management?

Dr Derman: The greatest challenge for payers is balancing the substantial clinical benefits of CAR T-cell therapies and bispecific antibodies with their high costs, supportive care requirements, and expanding use earlier in the disease course. As these therapies continue to move into earlier lines of treatment, the eligible patient population will expand considerably, increasing the potential budget impact despite the meaningful improvements in progression-free and overall survival.

Appropriate utilization management will require greater nuance than simply counting prior lines of therapy. Coverage policies should account for prior treatment exposure and refractoriness, disease tempo, comorbidities, functional status, target availability, toxicity risk, treatment logistics, and patient preferences.

Policies should also recognize that CAR T-cell therapy and bispecific antibodies are not interchangeable. CAR T-cell therapy offers the potential for a treatment-free interval but requires access to specialized treatment centers, manufacturing time, bridging therapy, and substantial upfront resources. Bispecific antibodies are more readily available but may require prolonged treatment, frequent monitoring, infection prophylaxis, immunoglobulin replacement, and ongoing drug administration.

Timely access is particularly important because patients with relapsed multiple myeloma can deteriorate rapidly. Lengthy prior authorization processes or rigid sequencing requirements may cause patients to miss the window during which they remain eligible for cellular therapy. Payers can reduce this risk by implementing expedited review processes, establishing clear and transparent coverage criteria, authorizing treatment promptly once a treatment decision has been made, and covering both bridging therapy and the supportive care required to deliver these therapies safely.

An additional challenge is that some patients have insurance plans that exclude or inadequately cover cell and gene therapies. Because CAR T-cell therapy may be covered under a separate cell and gene therapy benefit, a patient may meet all clinical eligibility criteria yet still be denied treatment because the employer-sponsored health plan did not purchase that benefit. This creates a particularly troubling form of inequity, in which access depends not only on medical need but also on the specific benefit design selected by a patient's employer.

Acquisition costs represent only one component of the total financial impact of these therapies. Patients receiving CAR T-cell therapy or bispecific antibodies frequently require immunoglobulin replacement, infection prophylaxis, laboratory monitoring, and other supportive care. Immunoglobulin replacement has become an increasingly important challenge because of its high cost, recurrent administration, and variable insurance coverage.

Although CAR T-cell therapy requires substantial upfront resources, it also offers the potential for a prolonged treatment-free interval and the downstream cost savings associated with durable responses. In contrast, most bispecific antibodies are currently administered continuously until disease progression or unacceptable toxicity, and it remains uncertain whether these therapies can be used effectively in a time-limited manner. Establishing evidence-based treatment discontinuation strategies for bispecific antibodies could meaningfully reduce cumulative toxicity, treatment burden, and overall costs.

The guideline acknowledges that the optimal sequencing of multiple myeloma therapies remains uncertain as new treatments continue to emerge. How should payers and oncology practices approach treatment sequencing today, and what additional evidence would most help inform future coverage decisions?

Dr Derman: In the absence of definitive sequencing data, payers and oncology practices should avoid rigid treatment algorithms. Sequencing decisions should account for prior drug exposure and refractoriness, the depth and duration of previous responses, disease tempo, cytogenetic risk, comorbidities, anticipated toxicities, treatment logistics, and patient preferences. Whenever possible, selecting a therapy with a different mechanism of action or target may be advantageous, but this should not become an inflexible coverage requirement.

Importantly, prior treatment directed against a particular antigen does not necessarily eliminate the potential benefit of targeting that antigen again. Patients may respond to a second B-cell maturation antigen (BCMA)-directed therapy, including a different BCMA-directed CAR T-cell therapy or a BCMA-targeted bispecific antibody. Selected patients may also benefit from a second CAR T-cell infusion or product. Prior target exposure should inform treatment sequencing but should not dictate it.

The evidence most needed includes prospective studies comparing sequences of BCMA-targeted therapies; outcomes after retreatment against the same target; predictors of response to a second CAR T-cell therapy; the effects of the interval and intervening treatment between BCMA-directed therapies; and comparative data evaluating repeated BCMA targeting versus switching to another target, such as G protein–coupled receptor class C group 5 member D (GPRC5D).

Real-world evidence will remain particularly valuable because treatment sequencing is evolving more rapidly than randomized clinical trials can evaluate.

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