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Pulled Myeloma Drug May Have a Role in Treating the Disease After All

— Belantamab mafodotin boosts PFS by nearly 2 years when combined with bortezomib, dexamethasone

MedpageToday
A computer rendering of monoclonal antibody treatment in multiple myeloma

A little more than a year after belantamab mafodotin (Blenrep), an anti-B-cell maturation antigen (BCMA) monoclonal antibody, for patients with relapsed/refractory multiple myeloma, results from the phase III suggested that there may still be a place for the agent.

The median progression-free survival (PFS) was 36.6 months for patients who received belantamab plus bortezomib (Velcade) and dexamethasone (BVd) compared with 13.4 months for those who received daratumumab (Darzalex) plus bortezomib and dexamethasone (DVd; HR 0.41, 95% CI 0.31-0.53, P<0.00001), reported María-Victoria Mateos, MD, PhD, of the Hospital Universitario de Salamanca in Spain, during an American Society of Clinical Oncology (ASCO) Virtual Plenary.

The 18-month PFS rates were 69% and 43% with BVd and DVd, respectively, and PFS was improved across all prespecified subgroups. Mateos specifically noted this included patients who were refractory to lenalidomide (Revlimid; HR 0.37, 95% CI 0.24-0.56), as well as those with high-risk cytogenetics (HR 0.36, 95% CI 0.22-0.58).

"BVd was superior to DVd in terms of progression-free survival -- the primary endpoint -- but also across the different key secondary endpoints of overall survival [OS], response rate, MRD [minimal residual disease] negativity rate, and durability of response, with an acceptable safety profile," Mateos said. "All these results suggest that BVd can be a potential new standard of care in second-line relapsed/refractory multiple myeloma, owing to its robust efficacy, manageable safety, and ease of administration."

At a median follow-up of 28.2 months, median OS was not reached in either arm, with an early trend favoring BVd (HR 0.57, 95% CI 0.40-0.80, P=0.0005), and overall response rates were 82.7% with BVd and 71.3% with DVd. The median duration of response was 35.6 months and 17.8, respectively, and the MRD negativity rate was higher with BVd versus DVd (38.7% vs 17.1% among patients with a very good partial response or better, and 24.7% vs 9.6% among those with a complete response).

In August 2020, the FDA for the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

However, after the DREAMM-3 confirmatory trial failed to meet the primary endpoint of PFS, the FDA requested that GSK, the agent's developer, withdraw it from the market.

The DREAMM-7 results "are compelling, and support the clinical efficacy of belantamab mafodotin for patients with relapsed/refractory multiple myeloma," said ASCO discussant Rachid Baz, MD, of the Moffitt Cancer Center in Tampa, Florida.

He observed that while the field of BCMA-directed therapies is becoming more crowded, treatment considerations should not only include efficacy and tolerability, but also access to care.

"It is important to note that while bispecifics and CAR [chimeric antigen receptor] T cells are required to be done in a setting where cytokine release syndrome can be managed -- usually large academic centers or large practices -- belantamab mafodotin can be administered in a community setting," he added.

This study included 494 patients. Median age was 64-65 years, and 12% to 15% were 75 years or older. Over half of patients in each group were men, and the majority were white. They had received at least one prior line of therapy, with about half receiving two or more lines. Most received prior bortezomib, and 52% in each arm received prior lenalidomide.

Adverse events (AEs) leading to permanent discontinuation of any treatment occurred in 31% of patients in the BVd arm and 19% of those in the DVd arm.

Mateos reported that blood and lymphatic system disorders of all grades were reported in 76% of patients in the BVd arm (62% ≥grade 3) and 64% in the DVd arm (44% ≥grade 3). Infections and infestations occurred in 70% (31% grade≥3) and 67% (20% grade≥3), respectively.

Ocular AEs including blurred vision, dry eye, eye irritation, and visual impairment were reported in 79% of patients in the BVd arm (34% ≥grade 3) and 29% of patients in the DVd arm (3% ≥grade 3).

These AEs -- a known risk with belantamab mafodotin -- were "generally reversible," Mateos noted, and managed with dose modifications. About 9% of patients discontinued treatment due to an ocular event.

During his discussion, Baz said the study raises some unanswered questions, and noted that BCMA CAR-T therapy and bispecifics have been approved for multiple myeloma after four previous lines of therapy.

"Where would BVd fit -- if approved -- if BCMA or bispecifics are approved in an earlier line?" he wondered.

Another question, he suggested, would be the mechanism of resistance to belantamab and how previous exposure would impact future therapy.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was sponsored by GSK.

Mateos reported honoraria from AbbVie/Genentech, Amgen, Celgene, GSK, Janssen-Cilag, Sanofi, and Takeda, and consulting or advisory roles with AbbVie, Amgen, Celgene, GSK, Janssen-Cilag, Pfizer, Regeneron, Roche/Genentech, and Takeda.

Baz reported honoraria from Hikma Pharmaceuticals; consulting or advisory roles with Bristol Myers Squibb, Sanofi, Janssen, and Pfizer; research funding from Karyopharm Therapeutics, AbbVie, Janssen, Bristol Myers Squibb, Daiichi Sankyo/Lilly, Seagen, Regeneron, Zymeworks, Arvinas, Marker Therapeutics, Pionyr, and Quantum Leap Healthcare Collaborative.

Primary Source

American Society of Clinical Oncology

Mateos M-V, et al "Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma" ASCO Virtual Plenary 2024; Abstract 439572.