INDIANAPOLIS—A number of drugs have recently been approved or are in clinical trials for treatment of relapsed/refractory multiple myeloma. Among them, belantamab mafodotin (Belamaf) has demonstrated the ability to eliminate myeloma cells both by direct cytotoxicity and by stimulating a systemic anti-tumor immune response. The immune aspect raised the question of whether the drug’s effectiveness could be enhanced by combining it with an immune checkpoint inhibitor (ICI).
To find out, a team of international researchers led by Attaya Suvannasankha, MD, of the Roudebush VAMC in Indianapolis undertook the DREAMM-4 study to evaluate the safety and efficacy of belamaf with pembrolizumab, an ICI. The phase I/II study of adults with relapsed/refractory multiple myeloma (RRMM) who had previously received three or more lines of therapy, including an anti-CD38 monoclonal antibody, a proteasome inhibitor and an immunomodulator.
In the first part of the study, the investigators established a dose of Belamaf of 2.5 mg/kg with pembrolizumab 200 mg, both delivered intravenously for up to 35 cycles. The team defined a primary endpoint of investigator-assessed overall response rate defined as partial response or better based on International Myeloma Working Group (IMWG) criteria. Other endpoints included duration of response, progression-free survival, adverse events, and pharmacokinetics.
Suvannasankha presented results of the study at the American Society of Clinical Oncology annual meeting in June. The primary analysis included all treated patients, six in part 1 and 28 in part 2 for 34 in total. Patients in both parts of the study had a median of five prior lines of therapy, with the number ranging from a minimum of three to a maximum of 13. Ten patients had high-risk cytogenetics and nine had extramedullary disease.
The researchers determined the overall response rate was 47%, with 10 out of 16 responders having at least very good partial response. With a median follow-up of 14.7 months, the median duration of response was eight months (2.1 months to not reached) and median progression-free survival was 3.4 months (1.4 months to 5.6 months).
Nearly all participants (97%) experienced at least one adverse event of any grade. Two-thirds (65%) of patients had a grade 3 or greater treatment-related adverse event. Adverse events experienced by 35% or more of the participants included keratopathy, blurred vision, and thrombocytopenia. Adverse events delayed doses in two-thirds of participants and resulted in dose reductions, but not discontinuation, in 32%. Nine patients had a serious adverse event, of which four had one or more serious adverse events related to treatment. Immune-related adverse events included gout and autoimmune hypothyroidism which occurred in two patients at grade 1. Preliminary pharmacokinetics were similar to belamaf therapy alone.
The researchers concluded that Belamaf plus pembrolizumab “demonstrated a favorable ORR compared with single-agent Belamaf in heavily pre-treated RRMM. No new TRAEs were identified; AE frequency and severity were similar to single-agent belamaf.
- Suvannasankha A, Bahlis NJ, Trudel S, Weisel K, Koenecke C, Rocafiguera Ao, Voorhees PM, Alonso AA, Callander NS, Mateos MV, Reddy N, Hakim S, Patel N, Williams D, Jewell RC, Zhou X, Gupta IV, Nooka AK. Safety and clinical activity of belantamab mafodotin with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM): DREAMM-4 Study. J Clin Oncol 40, 2022 (suppl 16; abstr 8018).
