In an interview with Pharmacy Times®, Saad Usmani, MD, MBA, FACP, FASCO, myeloma specialist and cellular therapist at Memorial Sloan Kettering Cancer Center, discusses emerging strategies for newly diagnosed multiple myeloma (NDMM) treatment based on his presentation of results from the phase 3 CEPHEUS clinical trial, presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting in Chicago, Illinois.
Usmani highlights the potential for fixed-duration therapies based on sustained minimum residual disease negativity, revealing that most patient subgroups benefit from daratumumab (D; Darzalex; Johnson & Johnson) plus bortezomib (Velcade; Takeda Oncology), lenalidomide (Revlimid; Bristol Myers Squibb), and dexamethasone (VRd; DVRd) treatment, with nearly 70% remaining progression-free at 4.5 years in CEPHEUS. While toxicity profiles remain similar across treatment regimens, Usmani explains the need for careful patient monitoring and supportive care, particularly for older and frailer patient populations.
Pharmacy Times: Were there any notable differences in toxicity profiles, including infection rates or cytopenias, between DVRd and VRd in the treatment-ineligible (TIE) subgroup, particularly given the older median age and frailty considerations?
Saad Usmani: When we compared the safety profile of the quadruplet versus triplet regimen in CEPHEUS for the transplant-ineligible patient population, we didn't notice any differences in the rates of all treatment-emergent adverse events (TEAEs) grade 3, 4, or higher. Any serious TEAEs that occurred were also very similar. Neutropenia rates were probably a little higher numerically, so was thrombocytopenia, but if you look at anemia and the presence of fatigue, those were kind of similar. COVID-19, because this was during the pandemic, the incidence of COVID-19 infection was higher, but if we look at pneumonia, it was around 14% versus 12%. Overall, somewhat similar, even in this older, frailer patient population.
Key Takeaways
- Fixed-duration treatment strategies are likely the future of multiple myeloma management, with sustained MRD negativity potentially enabling treatment duration optimization.
- Most patient subgroups showed benefits from DVRd, with consistent progression-free survival rates, though high-risk subsets require further investigation.
- Toxicity profiles between quadruplet and triplet regimens remained similar, with only slight increases in neutropenia and thrombocytopenia, suggesting the approach is manageable for transplant-ineligible patients.
Pharmacy Times: For pharmacists managing these regimens, are there specific supportive care measures you’d recommend to mitigate the higher intensity of a four-drug regimen in TIE patients?
Usmani: I would say that keeping an eye on the blood counts and adjusting the bortezomib and lenalidomide dosing become very important. Also, utilizing growth factor support, especially granulocyte colony-stimulating factor (G-CSF), for patients who might be borderline neutropenic may be important as well. And then prophylaxis for varicella-zoster virus (VZV) infection or for deep vein thrombosis (DVT) becomes very important for our pharmacists to pay attention to.
Pharmacy Times: How does DVRd compare to other daratumumab-based regimens like D-Rd (from MAIA) for TIE patients, and is there a clinical scenario where you would still favor D-Rd over DVRd?
Usmani: I think for the older, frail patients, especially those who are over the age of 75 years and are frail by the International Myeloma Working Group frailty score (IMWG), I would favor DRd, especially if they have standard-risk disease. I think the DRd regimen, as we studied in MAIA, is very appropriate for those patients. In some patients who have higher-risk disease, even in those older patients, I may consider using a dose-attenuated, less frequent dosing of bortezomib to ensure that we are optimizing those patients in terms of getting a good response and reducing the disease burden.
Pharmacy Times: Are there ongoing or planned studies exploring DVRd in broader NDMM populations, such as real-world cohorts or patients with higher frailty scores, and what additional data would you like to see to further define DVRd’s role in TIE NDMM?
Usmani: What is super important to know in the field of oncology is, when we do these clinical trials for regulatory approval, we also learn things along the way. One of the important lessons we've learned is that many of the real-world patients would not have made it to clinical trials because of some ineligibility. In the real world, we end up modifying or tweaking the regimen to help facilitate patients getting the appropriate treatment. I do feel that there are several real-world efforts going on right now that will help us in managing our patients better with quadruplet induction regimens, both for the transplant-eligible as well as the transplant-ineligible patients.
As examples, the American Society of Hematology (ASH) Research-Collaborative (ASH-RC) Multiple Myeloma Data Hub Network is looking at a cohort of patients who are getting real-world treatment with quadruplets. There are other analyses being done looking at the CEPHEUS, PERSEUS, or MAIA clinical trial data compared with the existing, commercially available data sets like Flatiron, etc, doing some indirect comparisons there. I do feel that efforts like ASH-RC would be very important in figuring out which patients benefit the most and how we are best able to utilize these regimens for patients in the real world.
