(OA-38) A Phase I/II Single Arm Study of Belantamab Mafodotin, Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma (Mm): Primary Analysis. Amarc 19-02 Belacard Study

An increasing number of patients with MM are lenalidomide-refractory and double or triple-class exposed at first relapse, underscoring the need for novel agents with distinct mechanism of action.  Belantamab Mafodotin (Belamaf, B), a first-in-class anti-BCMA antibody-drug conjugate, has demonstrated efficacy in heavily pretreated relapsed/refractory MM (RRMM). Its combination with carfilzomib and dexamethasone (Kd) may provide anti-myeloma synergistic activity. Here, we report the primary analysis of the BelaCarD study.

Methods:

BelaCarD is an ongoing, single-arm, multicentre phase I/II study evaluating an 8-weekly dosing schedule of B in combination with Kd in patients (pts) with RRMM after 1-3 lines of therapy. Treatment continues until disease progression. Corneal adverse events (AEs) are graded using the keratopathy and visual acuity (KVA) scale; all other AEs are assessed per CTCAEv5. The primary objective is progression free survival (PFS).

Results:

As of Aug 2023, 70 patients have been enrolled. The median age was 69.8 years (range: 48-81); 27.1% had high-risk cytogenetics and 77.2% had received 2-3 prior lines of therapy. Double- and triple-class refractory disease were present in 11.4% and 8.6% of patients, respectively.

Patients received a median number of 11 treatment cycles (range: 1-38). At primary analysis, 67% had discontinued therapy, primarily due to disease progression (40%). Treatment-related adverse events (AEs) occurred in 91% of patients, with grade (Gr) ≥3 in 70%. Grade ≥3 haematologic toxicity and infections occurred in 41% and 39.4%, respectively. Serious AEs (SAEs) were reported in 71%. Ocular symptoms (Blurred vision, photophobia, pain and dry eyes) occurred in 94%, with grade ≥3 events in 12.8%. KVA-defined ocular AEs were observed in majority of patients; BCVA reduction (any grade: 81.4%; grade 3: 37.1%; grade 4: 1.4%) and keratopathy (any grade: 75.7%; grade 3: 51%; grade 4: 0%). BCVA decline to 20/50 or worse in both eyes occurred in 8.5%.

Overall, 78.6% (95% CI: 66.8 – 87.7%) achieved at least a partial response (PR) within the first two cycles, including very good PR (VGPR) or better in 34.3% (95% CI: 23.1 – 46.9%). The overall response was 82.9% (95% CI: 71.7 – 91.0) with a complete response rate of 41.4% (95% CI: 29.5 – 54.2). At a median follow-up of 27.4 months, the median PFS was 22.6m (95% CI: 8.7 – 31.2 months) with 12- and 24-months PFS of 56.2% (95% CI: 43.7 – 67.0%) and 48.9% (95% CI: 36.2 – 60.4%). Median overall survival (OS) was not reached (95% CI: 32.6 – NA) with 12- and 24-month OS rates of 79.6% (95% CI: 68.0 – 87.4%) and 70.5% (95% CI: 57.5 – 80.2%).

Conclusions:

The primary analysis of the BelaCarD study demonstrates that BKd with an extended B dosing-schedule is effective and tolerable. These findings, alongside with other studies incorporating belantamab mafadotin into standard-regimen back-bones, support its potential role in early lines of therapy for RRMM.