Novel Antibody-Drug Conjugate Under Study in Combination Therapy for Resistant Myeloma
Posted: Monday, November 22, 2021
The antibody-drug conjugate indatuximab ravtansine may enhance the antitumor activity of lenalidomide for patients with relapsed or refractory multiple myeloma, according to a phase I/IIa study conducted by Kenneth C. Anderson, MD, of Harvard Medical School, Boston, and colleagues. In fact, administration of indatuximab ravtansine in combination with immunomodulatory drugs was reported to have a manageable toxicity profile, with most treatment-related adverse events being grade 1 or 2. The findings of this open-label, multicenter trial were published in The Lancet Haematology.
“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,” stated the study investigators.
Patients with relapsed or refractory multiple myeloma with an Eastern Cooperative Oncology Group performance status or Zubrod score of 2 or below were enrolled. Patients who had failed to respond to one therapy received indatuximab ravtansine with lenalidomide and dexamethasone. Patients who had progressive disease within 60 days of their last treatment and failed to respond to at least two therapies received indatuximab ravtansine with pomalidomide and dexamethasone. Phase I consisted of intravenous indatuximab ravtansine cycles in escalating doses (up to 120 mg/m2). Phase I indicated that the maximum tolerated dose of indatuximab ravtansine plus lenalidomide was 100 mg/m2, and subsequently this dose was used in phase II.
Objective response and clinical benefit response appeared to be similar in patients who received indatuximab ravtansine plus lenalidomide (71.7% and 85%, respectively) versus indatuximab ravtansine plus pomalidomide (70.6% and 88%, respectively). The most common adverse events of grade 3 or 4 were neutropenia, anemia, and thrombocytopenia, and treatment-associated adverse events led to discontinuation of therapy in 55% of patients.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.