Early-Phase Research on Daratumumab-Based Therapies for Resistant Myeloma

By: Vanessa A. Carter, BS
Posted: Wednesday, February 2, 2022

A phase I/II study conducted by Jonathan L. Kaufman, MD, of Winship Cancer Institute, Emory University School of Medicine, Atlanta, and colleagues evaluated the safety and efficacy of venetoclax versus bortezomib in patients with relapsed or refractory multiple myeloma and t(11;14). Their preliminary results, presented during the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 817), suggest that venetoclax and bortezomib demonstrated a tolerable safety profile when combined with daratumumab and dexamethasone.

This multicenter, dose-escalation and -expansion study enrolled 34 patients with t(11;14) relapsed or refractory multiple myeloma. Participants were randomly assigned to receive daratumumab and dexamethasone plus 400 mg (n = 11) or 800 mg (n = 7) of venetoclax or 1.3 mg/m² of bortezomib (n = 16).

The most common adverse events included fatigue, nausea, insomnia, and diarrhea. Adverse events of grade 3 or 4 were mainly hematologic toxicities, and no grade 3 or 4 infections were reported in more than two treatment groups. Serious adverse events such as non-cardiac chest pain, femur fracture, febrile neutropenia, and tonsil cancer were reported in one individual each in the venetoclax arm. In the bortezomib arm, however, two patients were observed to have multiple events.

Based on daratumumab exposure at the time of data cutoff, the median treatment duration was 6.5, 5.6, and 3.9 months with 400 mg of venetoclax, 800 mg of venetoclax, and bortezomib, respectively; the preliminary objective response rates were 72.7%, 100%, and 62.5%. Notably, the preliminary rate of a very good partial response or better was 72.7% for patients given 400 mg of venetoclax, 100% for those given 800 mg of venetoclax, and 31.3% for individuals given bortezomib.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.

2021 ASH Annual Meeting & Exposition

---