Blenrep Combo Lengthens Time to Progression in Relapsed, Refractory Myeloma

Patients with relapsed/refractory multiple myeloma tended to live longer without their disease worsening (progression-free survival; PFS) when treated with Blenrep (belantamab mafodotin-blmf) plus Pomalyst (pomalidomide) and dexamethasone — a regimen referred to as BPd — compared to those treated with Velcade (bortezomib) plus Pomalyst and dexamethasone (PVd), according to findings from the phase 3 DREAMM-8 trial.

Data from the trial were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

The median PFS was not reached in the BPd arm, meaning that not enough patients experienced progression for the researchers to calculate an average time to death or progression, compared with 12.7 months in the PVd arm. At 12 months, the PFS rate was 71% and 51% in each respective arm. Findings also highlighted that treatment with BPd reduced the risk of progression or death in difficult-to-treat subgroups, which included patients with cytogenic or functional high-risk disease; refractory disease following Revlimid (lenalidomide); and previous treatment with anti-CD38 therapy.

The overall response rate (ORR; percentage of patients whose disease shrinks or disappears) with BPd was 77% vs 72% with PVd, with complete responses (CRs; disappearance of cancer) reported in 40% and 16% of patients, respectively.

In each respective arm, minimal residual disease (MRD) negativity was observed in 23.9% and 4.8% of those with a CR or stringent CR (no myeloma cells detected in the bone marrow or urine) and in 32.3% and 5.4% of patients with a CR, stringent CR, or very good partial response (VGPR; 90% or more decrease in a myeloma-related protein). MRD is a tool that informs myeloma prognosis. MRD negativity indicates that treatment is working and is defined as having an absence of myeloma cells in the bone marrow cells.

Additionally, the median duration of response (DOR; length of time cancer therapies work) was not reached vs 17.5 months, in the BPd and PVd groups, respectively.

Data showed that the median time to a second relapse (known as PFS2) was not evaluable in the BPd group and was 22.4 months in the PVd group. The median overall survival (OS; time from treatment until death of any cause) was not evaluable with both the Blenrep triplet and Velcade-based. Investigators will continue to follow up with patients for additional OS data for future pre-specified analyses.

“Taken together with the results of phase 3 DREAMM-7, which combined [Blenrep] with [Velcade] and dexamethasone, these data highlight the potential of [Blenrep]-containing triplets to address an unmet need for novel regimens to treat patients with myeloma and first relapse,” study investigator Dr. Suzanne Trudel, a clinician scientist at Princess Margaret Cancer Centre, said in the presentation.

In the international phase 3 DREAMM-8 trial, 302 patients were randomly assigned to receive treatment in the BPd arm (155 patients) or the PVd arm (147 patients).

The trial’s main goal was PFS per independent review committee assessment, meaning that the experts reviewing the data were not associated with the study and did not know which therapy patients received. Secondary end points included OS, MRD negativity, DOR, ORR, CR rate, time to response, time to progression, PFS2, side effects and eye-related findings.

Adults with multiple myeloma who received at least one prior line of therapy containing Revlimid were eligible for enrollment on the trial. Other requirements for study entry included having progressive disease during or following the most recent line of treatment and no prior therapy with anti-BCMA agents or Pomalyst.

Any-grade side effects affected more than 99% of patients in the BPd arm and 96% of those in the PVd arm, with 91% and 73% experiencing moderate to severe (grade 3/4) side effects in each respective group. Following side effects, 91% and 75% of patients had dose interruptions or delays, 61% and 61% had dose reductions, and 15% and 12% had permanent treatment discontinuation. Fatal side effects were reported in 11% of patients in each treatment arm.

Of note, ocular events were manageable with dose delays and reductions, and 9% of those in the BPd arm discontinued treatment due to occurring events.

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