'The HemOnc Pulse Live': Controversies in Frontline Myeloma

By Saad Z. Usmani, MD, MBA, FACP, Peter Voorhees, MD, Shambavi Richard, MD, Binod Dhakal, MD, Caitlin Costello, MD - Last Updated: July 3, 2025

In this episode of The HemOnc Pulse, Saad Z. Usmani, MD, MBA moderates a comprehensive discussion on current and emerging strategies in the frontline treatment of multiple myeloma during the HemOnc Pulse Live! event held recently in Austin, TX. The conversation begins with a presentation by Caitlin Costello, MD, associate professor of medicine at the University of California, San Diego, who outlines the rationale behind frontline quadruplet therapy and the evolving role of transplant in newly diagnosed patients.

Dr. Costello reviews the goals of induction therapy, emphasizing the need for rapid and deep disease control while preserving future treatment options. Historically, transplant eligibility was determined by subjective assessment; however, the field is now shifting toward a more nuanced approach that considers whether a patient is transplant-intended or transplant-deferred. The discussion includes consideration of long-term planning and therapeutic sequencing to maximize efficacy and durability of response.

Evidence from recent clinical trials, including the phase 2 MASTER trial (NCT03224507) and the phase 3 PERSEUS study (NCT03710603), support the use of quadruplet therapy incorporating CD38 monoclonal antibodies, immunomodulatory agents, proteasome inhibitors, and corticosteroids. These regimens have demonstrated improvements in progression-free survival and deep responses, including minimal residual disease (MRD) negativity. MRD status is gaining traction as a surrogate endpoint in clinical trials, with potential implications for treatment de-escalation and duration.

Following Dr. Costello’s presentation, a panel of experts explores the role of proteasome inhibitors in induction regimens, with particular attention to the substitution of carfilzomib for bortezomib. Data from single-arm studies, including MASTER and other carfilzomib-based trials, suggest favorable outcomes and raise the question of whether carfilzomib may offer an advantage in the frontline setting, as it has in relapsed disease.

Panelists:

  • Binod Dhakal, MD, Medical College of Wisconsin
  • Peter Voorhees, MD, Atrium Health Levine Cancer Institute
  • Shambavi Richard, MD, Mount Sinai

The panel provides expert commentary on the implications of these data for clinical practice. The discussion reflects the complexity of therapeutic decision-making in multiple myeloma and highlights the continued movement toward personalized and data-driven care in the frontline setting. Following this panel session, The HemOnc Pulse Live! included sessions on relapsed myeloma and smoldering myeloma.

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