Indatuximab ravtansine with lenalidomide or pomalidomide shows encouraging clinical activity for relapsed or refractory multiple myeloma, according to data from a phase 1/2a study published in the Lancet Haematology.
Indatuximab ravtansine is an antibody drug conjugate that targets CD138. Previous studies showed little activity with the drug as monotherapy, but prior phase 1/2a studies have determined a maximum tolerated dose.
This phase 1/2a study determined the safety, activity and pharmacokinetics of combination therapy with indatuximab ravtansine. The study included 64 patients with relapsed or refractory multiple myeloma. Patients who had failed at least 1 prior therapy received indatuximab ravtansine plus lenalidomide and dexamethasone (n=47 patients). Patients who had failed at least 2 prior therapies and had progressive disease within 60 days of their last treatment were given indatuximab ravtansine plus pomalidomide and dexamethasone (n=17 patients).
The study authors defined 100 mg/m² as the recommended phase 2 dose for indatuximab ravtansine for both groups.
A total of 33 patients (71.7%) had an objective response to indatuximab ravtansine plus lenalidomide. There were 6 more patients who had a minor response, leading to a clinical benefit rate of 85%.
There were 12 patients (70.6%) who had an objective response to indatuximab ravtansine plus pomalidomide. There were 3 more patients who had minor response, for a clinical benefit rate of 88%.
All patients in the study had at least one treatment-emergent adverse event (TEAE), but more than 90% of them were grade 1 or 2. Fatigue, diarrhea, and nausea were the most common TEAEs.
A total of 36 patients (56%) completed the study, while 28 (44%) withdrew. The median follow up was 24.2 months for patients receiving indatuximab ravtansine plus lenalidomide and 24.1 months for patients receiving indatuximab ravtansine plus pomalidomide.
The median time to progression in the indatuximab ravtansine plus lenalidomide group was 19.5 months and was 16.6 months in the indatuximab ravtansine plus pomalidomide group.
“Although there are many new therapies approved for relapsed or refractory multiple myeloma, including very recently the approval of chimeric antigen receptor T-cell therapy, indatuximab ravtansine remains a promising agent that targets a novel antigen and is easily administered as an outpatient infusion,” the authors wrote in their report.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Kelly KR, Ailawadhi S, Siegel DS, et al. Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study. Lancet Haematol. 2021;8(11):e794-e807. doi:10.1016/S2352-3026(21)00208-8