Host Saad Usmani, MD, chief of the myeloma service at Memorial Sloan Kettering Cancer Center in New York City, and Sagar Lonial, MD, FACP, professor and chair of the Department of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, explore the journey of the antibody-drug conjugate (ADC) belantamab mafodotin, the first B-cell maturation antigen (BCMA)-targeted ADC approved by the US Food and Drug Administration (FDA) for patients with relapsed or refractory myeloma.

Dr. Lonial noted the excitement around the approval given how few treatment options there were for this subgroup of patients.

“In the relapsed/refractory setting, it clearly demonstrated clinical benefit, with a significant fraction of patients responding,” adding that the therapy seemingly “ushered in the era of BCMA-directed therapies.”

Early experiences with the drug during the DREAMM-2 trial pointed to the possibility of flexible dosing given the length of remission in some patients.

“Some patients stayed in remission for a long period with just a few doses,” Dr. Lonial said.

The flexible dosing helped mitigate ocular toxicity without compromising treatment responses in patients, according to Dr. Lonial.

“It was incredibly gratifying to see patients with no other options, have really long remissions with less frequent dosing schedules,” he said. “I think at that time point, we didn’t fully appreciate the variability in the ocular side effects.”

However, the phase 3 DREAMM-3 trial, designed as a confirmatory study, failed to meet its statistical endpoints, primarily due to high censoring rates and questionable trial design.

“It clearly demonstrated benefit, but the study design put the drug in a difficult position,” Dr. Lonial said. As a result, the FDA withdrew belantamab from the market despite evidence of efficacy.

Enthusiasm for the drug has since been revived by more recent data from the DREAMM-7 and DREAMM-8 trials, which were large, randomized trials with over 400 patients. In the DREAMM-7 trial, investigators compared belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd) in patients who had progression of multiple myeloma after at least one line of therapy.1 In the DREAMM-8 trial, lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy received either belantamab mafodotin, pomalidomide, and dexamethasone (BPd), or else pomalidomide, bortezomib, and dexamethasone (PVd). 2

“Combining drugs is the optimal way,” Dr. Lonial said, referencing the DREAMM-7 and DREAMM-8 trials. “One of the key advantages is that this is a therapy you can give the same week you see the patient.”

The convenience and accessibility of ADCs make them an especially promising option for community physicians, particularly in areas where access to chimeric antigen receptor (CAR) T-cell therapy remains limited due to cost and infrastructure.

“Cellular therapy availability and cost will remain an issue,” Dr. Usmani said, adding that ADCs help bridge gaps in care outside academic centers.

As regulatory discussions unfold around the DREAMM-7 and DREAMM-8 data, it will be interesting to see if belantamab returns as a viable treatment option, and this time, as part of a combination regimen with a flexible dosing schedule.

“What I think may resurrect this drug, and what we’re really excited about, is the idea of combining [the therapies when we use them], and not giving them as single agents,” Dr. Lonial said. “Allowing yourself the flexibility of reducing the dosing schedule such that the average delivered dose of belantamab mafodotin is every six to eight weeks.”

Some patients stayed in remission for a long period with just a few doses.

References

1. Hungria V, Robak P, Hus M, et al. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090
2. Dimopoulos MA, Beksac M, Pour L, et al. Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma. N Engl J Med. 2024;391(5):408-421. doi:10.1056/NEJMoa2403407

Elias Jabbour, MD, and Naval Daver, MD, both of the University of Texas MD Anderson Cancer Center, discuss challenges in TP53-mutated acute myeloid leukemia (AML) in this SOHO Insider podcast episode. Despite advances in other molecular subsets, TP53 AML has seen little meaningful progress in more than two decades. It remains a particularly aggressive form, especially common in older adults and therapy-related cases. Not all TP53 mutations are the same; prognosis worsens with high allelic burden, adverse cytogenetics, or multiple mutations.

The episode also looks ahead to emerging strategies that may reshape post-transplant care. Early-phase studies are testing engineered natural killer and CAR T-cell therapies as a new kind of donor lymphocyte infusion. These treatments could be given repeatedly with lower risk of graft-versus-host disease, helping to control minimal residual disease and prevent relapse.

Finally, the discussion turns to SOHO’s expanding global mission. With meetings held in Spain, Italy, India and Lebanon, SOHO continues to share education and clinical insight around the world.

Listen to more podcast episodes.

Andrew Kuykendall, MD, of Moffitt Cancer Center in Tampa, Florida hosts a podcast on the latest news in myeloproliferative neoplasms (MPNs) with guest Gabriela Hobbs, MD, of Massachusetts General Research Institute.

The pair discuss treatment goals for patients with MPNs, especially as treatments evolve and become more targeted for treatment.

“As therapies get better, we can offer more to our patients,” Dr. Hobbs said.

One upcoming abstract of interest at ASCO® 2025 includes Dr. Kuykendall’s oral abstract, titled “Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV),” which will be available for attendees on June 1, 2025, the ASCO® 2025 website.

They also discussed patients’ heart risks and pulmonary hypertension, needing teamwork with other doctors.

“We really need to strengthen those relationships with other specialties,” Dr. Kuykendall said.

Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center in New York, and Gwen Nichols, MD, CMO of the Leukemia & Lymphoma Society discuss recent chimeric antigen receptor (CAR)-T cell therapy advancements and the current state of blood cancer research.

Recent trials have shown cures in pediatric acute lymphoblastic leukemia. In myeloma, there has been an “amazing number of advances” by integrating multiple therapies, Dr. Nichols said.

The impact of CAR-T is broadening, paving the way for potential cures in other blood cancers and diseases, she said during the recording.

“We’re curing not only children with leukemia, but now other diseases,” Dr. Nichols said, but warned that research funding cuts could stall young scientists and US innovation.

“The US was the place for great research… people are leaving, and that brain drain will be real,” she warned on the podcast.

Jerald Radich, MD, of Fred Hutchinson Cancer Center in Seattle, sits down with Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center in New York, to reflect on progress made in chronic myeloid leukemia (CML) and the work still ahead to ensure equitable care worldwide.

“The issue with CML is that most of the CML in the world is in developing countries, and they can’t afford a drug, they can’t afford testing,” Dr. Radich said on the podcast.

The pair also discussed current funding cuts. “As a culture and a government, we’ve lost our imagination,” Dr. Radich said, adding that giving up the edge provided by our institutions for basic discovery “is not smart.”

Jerald Radich, MD, of Fred Hutchinson Cancer Center in Seattle, sits down with Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center in New York, to reflect on progress made in chronic myeloid leukemia (CML) and the work still ahead to ensure equitable care worldwide.

“The issue with CML is that most of the CML in the world is in developing countries, and they can’t afford a drug, they can’t afford testing,” Dr. Radich said on the podcast.

The pair also discussed current funding cuts. “As a culture and a government, we’ve lost our imagination,” Dr. Radich said, adding that giving up the edge provided by our institutions for basic discovery “is not smart.”