BPd Maintenance Safe, Yields Responses in High-Risk Multiple Myeloma

Patients with high-risk multiple myeloma who received BPd maintenance therapy reported no events of progression in the phase 2 trial.

Maintenance therapy with belantamab mafodotin (Blenrep), pomalidomide (Pomalyst), and dexamethasone (BPd) elicited deep responses and was well-tolerated in patients with high-risk multiple myeloma, according to an interim analysis of a phase 2 trial (NCT05208307) presented at the 22nd Annual International Myeloma Society Meeting and Exposition.

At the data cutoff date of August 31, 2025, in the 17 efficacy evaluable patients, baseline responses showed that 31.6% of patients had a stringent complete response (CR), 52.6% had a very good partial response (VGPR), and 15.8% had a partial response (PR). Best responses showed that 68.4% of patients experienced a stringent CR, 15.8% experienced a VGPR, and 5.3% experienced a PR. The median time to best response was 1.0 months (range, 0.43-13.8).

With 14 samples analyzed, minimal residual disease (MRD) negativity, defined by a next-generation sequencing with sensitivity of 10^-6, was achieved by 64.30% of patients; 88.9% of patients with MRD negativity achieved a CR or better rate, and 11.1% achieved a VGPR. When MRD negativity was defined with a sensitivity of 10^-5, it was achieved by 78.60% of patients; 90.9% of these patients achieved a CR or better, and 9.1% achieved a VGPR.

Additionally, with a median follow-up of 6 months from diagnosis and 15 months from diagnosis, 0% of the 17 evaluable patients reported any progression events.

“In patients with high-risk [multiple] myeloma, BPd combination maintenance has been shown to be safe, well-tolerated, and efficacious. The primary end point [of CR or better] was achieved in 68.4% of patients who are high-risk,” said lead study author Ajay K. Nooka, MD, MPH, FACP, associate director of clinical research at Winship Cancer Institute of Emory University. “In the [maximum tolerated dose (MTD) group], when patients receive belantamab [mafodotin] 1.9 mg/kg every 12 weeks, there were no grade 3 or 4 events.”

A total of 22 patients received treatment on day 1 of cycle 1 in the study. Eligible patients had high-risk multiple myeloma; presence of del(17p), t(4;14), and 1(14;16); primary plasma cell leukemia with at least 20% circulating plasma cells on peripheral blood; induction therapy of physician’s choice and status post autologous stem cell transplant; were enrolled within 6 months after transplant; and were eligible to receive maintenance treatment.

The median patient age was 59 years, the median time from diagnosis to study entry was 8.0 months, and the median time from autologous stem cell transplant to study entry was 2.5 months. A total of 52% of patients were male, 72% were White, 64% had immunoglobulin G, 60% had Revised International Staging System II.

Treatment consisted of intravenous belantamab mafodotin at 1.9 mg/kg at dose level zero, 1.4 mg/kg at dose level 1, and MTD at the expansion at MTD dose level on day 1 of every other 28-day cycle; pomalidomide was administered orally at 4 mg across all dose levels on days 1 to 21 of each 28-day cycle; and dexamethasone was administered orally at 40 mg across all dose levels on days 1, 8, 15, and 22 of each 28-day cycle. All therapy continued for 3 years or until disease progression.

Patients were also given the option to receive belantamab mafodotin at 1.9 mg/kg every 12 weeks after the first 2 doses, 8 weeks apart.

Notably, a safety run-in was conducted with the first 6 patients at the maximum planned dose; 1 dose-limiting toxicity was observed. The efficacy was analyzed using a mini-max 2-stage design.

An interim analysis will also be conducted after the first 19 patients are evaluable for response for futility.

The trial’s primary end point was the rate of CR or better. Secondary end points included PFS, VGPR or better, duration of response, overall survival, MRD, and safety.

In the safety run-in (n = 6), the most common grade 1 and 2 adverse events (AEs) were blurred vision (66.7%), dizziness (33.33%), peripheral motor neuropathy (33.33%), and diarrhea (33.33%); grade 3 or 4 AEs were hypoxia, blurred vision, thromboembolic event, pneumonitis, and vision decreased, all of which occurred in 1 patient (16.67%).

In the expansion at MTD dose level (n = 12), grade 1 and 2 AEs included blurred vision (58.33%), insomnia (33.33%), diarrhea (16.67%), muscle cramp (16.67%), and back pain (16.67%); no grade 3 or 4 AEs occurred.

“The current results support the exploration of BPd maintenance in future high-risk studies. The current study will expand to include 20 more patients with [the] new [International Myeloma Society-International Myeloma Working Group] high-risk definition,” concluded the study authors.

References

Nooka AK, Joseph NS, Parikh R, et al. Maintenance therapy with belantamab, pomalidomide and dexamethasone in high-risk myeloma patients: a phase 2 study with a safety run-in – interim analysis. Presented at: 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract OA-66.