Paul G. Richardson, MD, of Dana-Farber Cancer Institute, discusses the evolution of treatment for newly diagnosed multiple myeloma, with triplet regimens now being the standard of care, replacing the former doublet regimens. Key triplet combinations include bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) and carfilzomib (Kyprolis), lenalidomide, and dexamethasone (KRd), with additional promising results from combinations including daratumumab (Darzalex) or isatuximab (Sarclisa). Ixazomib (Ninlaro)-based regimens offer an oral treatment option, which is ideal for frailer patients or those unable to frequently visit infusion centers. He notes that the addition of anti-CD38 monoclonal antibodies like isatuximab has further improved response quality and depth, particularly for high-risk patients.
Aditya Bardia, MD, MPH, FASCO, of UCLA Health Jonsson Comprehensive Cancer Center, discusses the FDA approval of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for patients with pretreated HER2-low and -ultralow metastatic breast cancer, highlighting its impact on future HER2 testing strategies. The decision applies to patients with unresectable or metastatic, hormone receptor–positive HER2-low or -ultralow breast cancer who have progressed on at least 1 endocrine therapy. Bardia emphasizes the importance of evaluating HER2 expression by immunohistochemistry (IHC), as even minimal expression qualifies patients for treatment with the antibody-drug conjugate, although its efficacy in patients with HER2 IHC 0 disease remains uncertain. Ongoing trials, such as DESTINY-Breast15 (NCT05950945), are investigating the drug’s potential in patients with HER2 IHC 0 breast cancer, with future research efforts expected to further refine HER2-targeted treatments.
Ignacio Garrido-Laguna, MD, PhD, MBA, discusses the safety profile of daraxonrasib (RMC-6236) in patients with KRAS G12X–mutated pancreatic ductal adenocarcinoma (PDAC), based on updated data from an ongoing phase 1 study (NCT05379985). Among 127 patients treated at doses ranging from 160 mg to 300 mg, 98% experienced treatment-related adverse effects (TRAEs), with 29% having grade 3 or higher TRAEs. Rash was the most common toxicity, reported in 91% of patients, and dose modifications were needed in 35% to 42% of patients due to TRAEs, particularly rash. Proactive management strategies, including tetracyclines and supportive measures like topical steroids, are employed to mitigate rash. Further analyses are expected to refine the understanding of the drug’s toxicity profile.
Marco Ruella, MD, of University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, emphasizes the importance of ensuring cancer treatments, including CAR T-cell therapies are accessible to diverse patient populations—especially in multiple myeloma. He argues that although advanced therapies are frequently showcased at conferences like the ASH Annual Meeting, their real-world benefits remain unclear if they are not accessible to all patients. Ruella highlights that treatments limited to tertiary centers may exclude many patients, stressing the need to incorporate these therapies into community practices for broader access. At the 2024 ASH Annual Meeting, his team presented research showing that although minority health populations have equitable access to tertiary care, they face reduced access to commercial anti-BCMA CAR T-cell therapy.
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