KEY TAKEAWAYS
- The phase II trial aimed to evaluate the initial safety and efficacy of venetoclax combined with carfilzomib and dexamethasone compared to carfilzomib and dexamethasone alone in patients with t(11;14) RRMM.
- The primary objectives were to assess safety and efficacy. Secondary objectives were to assess PFS, OS, TTR, TTP, and DOR.
- The study showed promise in t(11;14) RRMM with good tolerability and >90% response rates.
Venetoclax, a promising BCL-2 inhibitor, showed an 80% overall response rate(ORR) in a Phase 2 study for relapsed/refractory multiple myeloma(RRMM), with higher response rates in patients with the t(11;14) translocation (92% vs. 75%).
Researchers aimed to evaluate the initial safety and efficacy of venetoclax combined with carfilzomib and dexamethasone compared to carfilzomib and dexamethasone alone in RRMM patients with t(11;14).
Patients with t(11;14)+ RRMM were randomly assigned in a 5:3:5 ratio to receive K (70 mg/m2 weekly) and d (40 mg) plus daily Ven (Ven400Kd or Ven800Kd) or Kd alone. The randomized cohort included individuals with at least one prior line of therapy (LOT), while those in the dose-finding stage had 1–3 prior LOT.
The primary objectives for the randomized part were safety and efficacy assessment, with secondary objectives including progression-free survival (PFS), overall survival (OS), time to response (TTR), time to progression (TTP), and duration of response (DOR).
The efficacy analysis included patients randomized to Ven400Kd, those enrolled during dose-finding, those randomized to Ven800Kd, and those randomized to Kd. Safety analysis involved individuals who received at least one dose of the study treatment.
About 48 randomized patients and 8 from dose-finding were analyzed (Ven400Kd, n=17; Ven800Kd, n=20; Kd, n=19); 1 patient in the Kd group did not receive treatment. Patients had a median age of 70.5–73 years, a median of 2 prior lines of therapy, and prior exposure to proteasome inhibitors (89–94%), immunomodulatory drugs (85–89%), and anti-CD38 monoclonal antibody (24−47%).
Treatment-emergent adverse events (TEAEs) occurring at ≥50% in any group (Ven400Kd vs Ven800Kd vs Kd) were diarrhea (65 vs 75 vs 6%), nausea (53 vs 55 vs 28%), fatigue (35 vs 50 vs 22%), and vomiting (0 vs 50 vs 11%). Grade ≥3 TEAEs occurred in 88%, 85%, and 72% of patients.
Grade ≥3 TEAEs occurring at ≥20% in any group were lymphopenia (18 vs 30 vs 6%), neutropenia (12 vs 25 vs 11%), and hypertension (24 vs 15 vs 17%). Few Grade ≥3 cardiac disorders occurred (0 vs 5 vs 6%). Grade ≥3 infection rates were higher in the VenKd groups vs Kd (29 vs 20 vs 11%).
At median follow-ups of 16.8 (5.8–30.8), 21.1 (2.2–65.8), and 11.5 (0.0–28.3) months for the Ven400Kd, Ven800Kd, and Kd groups, respectively, the corresponding overall response rates (ORRs) (95% CI) were 94% (71−100), 95% (75−100), and 58% (34−80). Complete response (CR)/stringent CR rates were 29%, 50%, and 11%, respectively.
The median time to response (TTR) was 1.0, 1.0, and 2.4 months. The 12-month PFS estimates were 67%, 85%, and 79%, with a median PFS of 42.4 months (HR vs Kd=0.613 [95% CI, 0.153–2.456]) in the Ven800Kd group and not reached (NR) in the Ven400Kd and Kd groups. Medians for OS, TTP, and DOR were not reached in any group. More mature data will be presented.
The study showed promise in t(11;14) RRMM with good tolerability and >90% response rates.
Source: https://imsannual2023.eventscribe.net/fsPopup.asp?PresentationID=1302336&mode=presInfo
Clinical Trial: https://clinicaltrials.gov/study/NCT02899052
Kaufman JL. First results from the randomized portion of a phase 2 study of venetoclax plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with t(11;14) relapsed/refractory multiple myeloma.
