The first-in-class BCMA-directed antibody-drug conjugate belantamab mafodotin-blmf (Blenrep) in combination with carfilzomib (Kyprolis) and dexamethasone (BKd) led to a high overall response rate (ORR) with a tolerable safety profile in patients with relapsed/refractory multiple myeloma, according to data from the phase 1/2 BelaCarD study (ACTRN12620000490976) that were presented during the
Findings from the primary analysis of the study demonstrated that patients who received the combination (n = 70) achieved an ORR of 83%. The very good partial response (VGPR) or better rate was 60%, the complete response (CR) rate was 41%, the VGPR rate was 19%, and the PR rate was 23%.
Moreover, at a median follow-up of 27.4 months, the median progression-free survival (PFS) was 22.6 months (95% CI, 8.7-31.2). The 12- and 24-month PFS rates were 56.2% (95% CI, 43.7%-67.0%) and 48.4% (95% CI, 35.6%-60.1%), respectively.
“This is the first stage of exploring the development of BKd,” Masa Lasica, MBBS, FRACP, FRCPA, a hematologist, clinical researcher, and the leader of the Indolent Lymphoma and Chronic Lymphocytic Leukaemia program at St Vincent’s Hospital in Melbourne, Australia, said during the presentation. “Despite the majority of the cohort [having received] 2 or 3 lines of [prior] therapy, it’s an effective option with an ORR of 83% and a median PFS of 22.6 months. The safety [profile] is what we would expect with the individual drugs.”
What Were the Key Design Characteristics of BelaCarD?
BelaCarD was an open-label, single-arm trial that enrolled patients with relapsed/refractory multiple myeloma following 1 to 3 prior lines of treatment.2 Patients needed to be at least 18 years old; have an ECOG performance status of 0 to 2; have measurable disease, and have adequate hematologic, hepatic, renal, and cardiac function.
All patients received intravenous (IV) belantamab mafodotin at 2.5 mg/kg on day 1 of cycle 1, then on day 1 of every second cycle. IV carfilzomib was given at 20 mg/m2 on day 1 of cycle 1, then at 70 mg/m2 on days 1, 8, and 15 of each subsequent cycle. Oral dexamethasone was administered weekly at 40 mg (20 mg for patients ages > 75 years) on days 1, 8, 15, and 22 of each cycle. Treatment occurred via alternating 28-day cycles.
The study included safety run-in and expansion phases.1 The safety evaluation occurred after the tenth patient completed 2 cycles of therapy. If no more than 3 patients experienced grade 4 toxicities in the first 2 cycles, the same treatment schedule was adopted for the eleventh patient onwards. The median belantamab mafodotin dose interval for the first 10 doses was 62 days (range, 59-89).
The primary end point was PFS. Secondary end points included ORR, overall survival (OS), minimal residual disease, and safety.
What Was the Safety Profile of BKd?
Any-grade adverse effects (AEs) occurred at a rate of 98%; 91% of patients had AEs that were deemed to be related to therapy. Grade 3 or higher AEs were reported in 87% of patients, and 70% of patients had AEs that were determined to be related to therapy.
Therapy-related AEs leading to permanent discontinuation occurred in 25% of patients; 7% each were related to belantamab mafodotin and carfilzomib, and 11% were related to both agents. Therapy-related AEs leading to dose delay (47%) or reduction (60%) were reported, as were serious AEs (71%) and therapy-related serious AEs (4%).
Any-grade treatment-emergent AEs (TEAEs) included nausea (35.71%), fatigue (34.29%), diarrhea (30.00%), insomnia (27.14%), and vomiting (25.71%). Grade 3 or higher TEAEs included hypertension (14.29%), insomnia (12.86%), and acute kidney injury (8.57%).
Any-grade hematologic and infectious AEs included upper respiratory tract infection (54%), COVID-19 (28%), and thrombocytopenia (35%). Grade 3 or higher AEs in these classifications included thrombocytopenia (24%), lower respiratory tract infection (14%), anemia (10%), and sepsis (10%).
In terms of ocular AEs, any-grade corneal findings (100%), best corrected visual acuity (98%), and blurred vision (50%) were reported. These AEs occurred at a grade 3 severity at respective rates of 51%, 37%, and 13%. The study authors noted that these effects were reversible and manageable with dose modifications.
What Were the Additional Efficacy Data From the BelaCarD Trial?
The estimated median OS was 36.3 months (95% CI, 32.6-not available); the 12- and 24-month OS rates were 79.6% (95% CI, 68.0%-87.4%) and 69.6% (95% CI, 56.1%-79.7%), respectively.
Data from a subgroup analysis showed that patients with ISS stage 1 disease (n = 32) had a significantly better median PFS compared with those with stage 2 or 3 disease (n = 37), at 29.5 months vs 8.2 months, respectively (P = .0055). Patients who were triple-class exposed (n = 15) experienced a median PFS of 8.2 months compared with 25.5 months among those who were not (n = 65; P = .0271). No significant different differences in PFS were reported with other prognostic factors, including high-risk cytogenetics (P = .0691), number of prior lines of therapy (P = .5763), bortezomib (Velcade)–refractory disease (P = .1596), lenalidomide (Revlimid)–refractory disease (P = .6342), or prior anti-CD38 monoclonal antibody exposure (P = .1109).
At the data cutoff, 47 patients were off treatment. Patients discontinued treatment due to disease progression (n = 29), AEs (n = 7), investigator or patient decision (n = 6), or death (n = 5).
“In summary, these results support belantamab mafodotin combinations in early-line therapy for [patients with] relapsed/refractory multiple myeloma,” Lasica said in her conclusion.
Disclosures: Lasica reported being on the advisory board of or receiving speaker honoraria from Janssen, AbbVie, Beigene, Sobi, and Recordati.
References
- Lasica M, Horvath N, Kim YJ, et al. Phase II single arm study of belantamab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: primary analysis of AMARC 19-02 BelaCarD study. Presented at: 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract OA-38.
- A phase I/II single arm study of combination belantamab mafodotin, carfilzomib, dexamethasone in patients with early relapsed multiple myeloma. Australian New Zealand Clinical Trials Registry. Updated April 22, 2024. Accessed September 20, 2025. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620000490976p