ABSTRACT
While significant strides have been made in the treatment of multiple myeloma, treatment options remain limited and definite, and most patients ultimately succumb to their disease. The urgency for more treatment modalities remains, as patients who are refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies have a median survival of only 5.8 to 13 months. Belantamab mafodotin, a first-in-class antibody-drug conjugate, was approved by the US Food and Drug Administration in 2020 for patients with relapsed or refractory myeloma who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. It produced an overall response rate of 31%, and the median progression-free survival was 2.9 months when administered as a single agent. While generally well tolerated, ocular toxicities were a notable adverse event reported. In this article, we discuss the response data, toxicity profile including ocular toxicities, and treatment management.
ABSTRACT
PURPOSE: In this study, the addition of ixazomib to lenalidomide maintenance post-autologous stem cell transplant (ASCT) in 64 patients with newly diagnosed multiple myeloma was evaluated on the basis of the observed benefit of lenalidomide-only maintenance in prior studies. PATIENTS AND METHODS: Patients were started on maintenance therapy with lenalidomide and ixazomib within 60-180 days of stem cell infusion. RESULTS: Response rates deepened over time from baseline post-ASCT for 39 patients. The complete response (CR)/stringent CR rate was 43% and median overall survival was not reached with a median follow-up of 62 months (range, 25-82 months). Median PFS (mPFS) for all patients was 73 months and has not been reached for those with International Staging System (ISS) stage 1 disease. mPFS in 9 patients who had ISS stage 3 disease and 14 patients who had high-risk cytogenetics was 34 and 25 months, respectively. Twenty-two patients had progressive disease, while 19 patients continue to receive dual maintenance. The most common grade 3/4 adverse events included neutropenia, leukopenia, thrombocytopenia, lung infections, diarrhea, and maculopapular rash. Second primary malignancies occurred in 9 patients. Toxicity led to dose reductions in ixazomib and lenalidomide in 20 and 31 patients, respectively. Discontinuation of ixazomib due to toxicity occurred in 4 patients. Grade 1/2 neuropathy occurred in 22 patients and led to reduction or discontinuation of ixazomib in 2 patients. CONCLUSIONS: The addition of ixazomib to lenalidomide maintenance demonstrated a better than expected PFS compared with historical data using lenalidomide alone and was safe and tolerable.
