Belantamab Mafodotin Regimen Bests Standard Care in Rel/Ref Multiple Myeloma

Belantamab mafodotin plus bortezomib and dexamethasone could be a new standard of care for second-line or later treatment of relapsed or refractory multiple myeloma, according to an ASCO Plenary Series presentation.

The presentation showed that, in the DREAMM-7 trial, belantamab mafodotin plus bortezomib and dexamethasone more than doubled progression-free survival (PFS) when compared to daratumumab plus bortezomib and dexamethasone.

The phase 3 DREAMM-7 trial (ClinicalTrials.gov Identifier: NCT04246047) included 494 patients with multiple myeloma who had received 1 or more prior lines of therapy but no prior treatment with an anti-BCMA therapy.

The patients were randomly assigned to receive belantamab mafodotin plus bortezomib and dexamethasone (n=243) or daratumumab plus bortezomib and dexamethasone (n=251). After 8 cycles, the patients switched to monotherapy with belantamab mafodotin or daratumumab, respectively. Baseline characteristics were generally well balanced between the treatment arms.

At a median follow-up of 28.2 months, the median PFS was 36.6 months with belantamab mafodotin and 13.4 months with daratumumab (hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P <.00001). The 18-month PFS rate was 69% and 43%, respectively.

This PFS benefit was consistent across prespecified subgroups, including in patients with lenalidomide-refractory disease and those with high-risk cytogenetics, said study presenter Maria-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca in Spain.

Although overall survival (OS) data were not yet mature, there was a trend toward improvement with belantamab mafodotin (HR, 0.57; 95% CI, 0.4-0.8; P =.00049). The 12-month OS rate was 87% with belantamab mafodotin and 81% with daratumumab. The 18-month OS rate was 84% and 73%, respectively.

“The median overall survival was not reached in either arm, and follow-up is ongoing,” Dr Mateos said.

The overall response rate was 82.7% with belantamab mafodotin and 71.3% with daratumumab. The rate of complete response (CR)/stringent CR was 34.6% and 17.1%, respectively. The rate of very good partial response (VGPR) or better was 65.8% and 46.2%, respectively.

Among patients with a VGPR or better, the rate of minimal residual disease (MRD) negativity was 38.7% with belantamab mafodotin and 17.1% with daratumumab. Among patients with a CR/stringent CR, the rate of MRD negativity was 24.7% and 9.6%, respectively.

The median duration of response was 35.6 months with belantamab mafodotin and 17.8 months with daratumumab. “The median values may increase with longer follow-up, as responses are ongoing for over half of patients” in the belantamab mafodotin arm, Dr Mateos noted.

Treatment-related adverse events (TRAEs) occurred in 100% of patients in the belantamab mafodotin arm and 95% of those in the daratumumab arm. Grade 3-4 TRAEs occurred in 90% and 67%, respectively. TRAEs led to treatment discontinuation in 26% and 15%, respectively. Fatal TRAEs occurred in 7 patients (3%) who received belantamab mafodotin and 2 patients (<1%) who received daratumumab.

Ocular events were more common with belantamab mafodotin (79%) than with daratumumab (29%). Grade 3-4 ocular events in the belantamab mafodotin arm included blurred vision (22%), dry eye (7%), eye irritation (5%), and visual impairment (5%). Nine percent of patients in the belantamab mafodotin arm discontinued treatment due to an ocular event.

Taken together, these results suggest that belantamab mafodotin plus bortezomib and dexamethasone “can be a potential new standard of care in second line-plus relapsed/refractory multiple myeloma, irrespective of prior exposure to immunomodulatory drugs or proteasome inhibitors,” Dr Mateos said.

“[T]he DREAMM-7 trial results are compelling and support the clinical efficacy of belantamab mafodotin for patients with relapsed/refractory multiple myeloma,” said study discussant Rachid Baz, MD, of Moffitt Cancer Center in Tampa, Florida.

Dr Baz did wonder about the optimal sequence of treatments and where the belantamab mafodotin combination would fit “in a crowded field of BCMA-directed therapy.” He pointed out, however, that belantamab mafodotin can be given in a community setting, unlike other BCMA-directed therapies, which must be administered in a setting where cytokine release syndrome can be managed.

Dr Baz also pointed out that belantamab mafodotin was previously approved to treat patients with relapsed/refractory multiple myeloma but was pulled from the US market in November 2022. This decision was based on results from the DREAMM-3 trial, which suggested that belantamab mafodotin was no more effective than treatment with pomalidomide and dexamethasone.

Disclosures: DREAMM-7 was supported by GSK. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. Dr Baz disclosed affiliations with AbbVie, Arvinas, Bristol Myers Squibb, Daiichi Sankyo/Lilly, GlaxoSmithKline, Hikma Pharmaceuticals, Janssen, Karyopharm Therapeutics, Marker Therapeutics, Pfizer, Pionyr, Quantum Leap Healthcare Collaborative, Regeneron, Sanofi, Seagen, and Zymeworks.

This article originally appeared on Cancer Therapy Advisor