According to the preliminary results from the expansion cohort of a phase 1/2 trial presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, venetoclax plus daratumumab and dexamethasone demonstrates (VenDd) a tolerable safety profile in patients with t(11;14) relapsed/refractory multiple myeloma (RRMM).

Although current therapies for MM delay disease progression and prolong survival, Jonathan L. Kaufman, MD Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, and colleagues note that many patients relapse or become refractory. However, treatment with the anti-CD38 antibody daratumumab, plus proteasome inhibitor bortezomib and dexamethasone, is approved for patients with MM who have recieved at least 1 prior line of therapy. Additionally, venetoclax demonstrated anti-myeloma activity in patients with t(11;14) RRMM

“Treatment of pts with t(11;14) RRMM using VenDd (part 1) and pts with RRMM (irrespective of t(11;14) status; part 2) with VenDvd [venetoclax plus bortezombib and dexamethasone] demonstrated a tolerable safety profile and an overall response rate (ORR) of 95.8% and 91.7%, respectively (J Clin Oncol). Part 3 further evaluates the safety and efficacy of VenDd vs DVd in pts with t(11;14) RRMM, with preliminary results presented here,” explained Dr Kaufman et al. 

With this in mind, researchers conducted part 3 of this multicenter, dose-escalation, and expansion study to evaluate the safety and efficacy of VenDd v.s. Dvd. Due to the increased incidence of infections amongst patients in the venetoclax arm of the BELLINI study (Lancet Oncol), researchers decided to expand this study to further interpret the patient safety profile.

To be eligible, patients must have received at least one prior line of therapy, including an immunomodulatory agent, and be non-refractory to PIs or anti-CD38 Ab. Patients were randomized 4:2:5 to receive either VenDd at 400 or 800mg or bortezomib and dexamethasone. 

A total of 11, 7, and 16 patients were enrolled in the venetoclax 400mg plus daratumumab and dexamethasone (Ven400Dd), Ven800Dd, and Dvd arms, respectively. The median prior lines of therapy were 1.0 (1-6) in Ven400D; 1.0 (1-3) in Ven800Dd; and 2.0 (1-3) in DVd. All patients in the Ven400Dd and Ven800Dd arms had an ECOG performance status of ≤1; 87.5% and 12.5% of pts in the DVd arm had an ECOG performance status of ≤1 and 2, respectively.

The median duration of treatment based on daratumumab exposure was 6.5, 5.6, 3.9 months for the Ven400Dd, Ven800Dd, and DVd arms, respectively. The preliminary ORR was 72.7%, 100%, and 62.5% for Ven400Dd, Ven800Dd, and DVd arms. The preliminary rate of very good partial response or better was 72.7%, 100%, and 31.3%, respectively. However, follow-up was immature, and results may deepen.

The most common adverse events (AEs) occurring in ≥5% of pts in ≥2 treatment groups included insomnia, fatigue, diarrhea, and nausea, while grade 3/4 AEs were primarily hematologic toxicities. However, no grade 3/4 infections occurred in ≥2 treatment groups.

Additionally, six patients experienced serious AEs. In the Ven400Dd arm, a femur fracture occurred in one patient and non-cardiac chest pain in another. Amongst those in the Ven800Dd arm, 1 patient had febrile neutropenia, and another had tonsil cancer. In the Dvd arm, a single patient had pyrexia and an upper respiratory tract infection, while another had hyperglycemia, autonomic neuropathy, distributive shock, disseminated cryptococcosis, and cytomegalovirus infection; no deaths were reported.

“The preliminary results from part 3 of this novel randomized, phase 2 study of t(11;14)-selected RRMM pts treated with VenDd vs DVd demonstrate a tolerable safety profile. Updated analyses, including response rates with longer follow-up and minimal residual disease status, will be included at presentation,” concluded Dr Kaufmen and colleagues. —Alexandra Graziano