Back Back
ASH 2023 Multiple Myeloma

CE / CME

Conference to Clinic: Expert Analysis of the Top Multiple Myeloma Abstracts From the 2023 ASH Annual Meeting

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurses: 1.00 Nursing contact hour

Physicians: maximum of 1.00 AMA PRA Category 1 Credit™

Pharmacists: 1.00 contact hour (0.1 CEUs)

Released: March 07, 2024

Expiration: March 06, 2025

Sagar Lonial
Sagar Lonial, MD, FACP
CME/CE Information

Activity

Progress
1 2
Course Completed

Update on Safety and Efficacy of VenDd vs DVd in t(11;14) R/R MM: Study Design

Sagar Lonial, MD, FACP:
Next, let’s move on to R/R myeloma, focusing on the 11;14 translocation t(11;14). Studies were presented at ASH 2023 on how these patients respond to treatment with venetoclax.

The first trial evaluated venetoclax with daratumumab and dexamethasone (VenDd) vs bortezomib with daratumumab and dexamethasone (DVd), which was previously shown to be effective for R/R multiple myeloma in the phase III CASTOR trial.14,15

This was a multicenter, dose-escalation/expansion phase I/II study14 that enrolled 81 adults with R/R multiple myeloma with progressive disease after at least 1 previous line of therapy. Fifty-five patients received VenDd and 26 received DVd. The primary endpoints were PFS and ORR, with MRD negativity and safety as secondary endpoints.

Download

Update of VenDd vs DVd in t(11;14) R/R MM: MRD Negativity

Sagar Lonial, MD, FACP:
I want to focus first on MRD negativity. At a cutoff of 10-5, 40% of patients overall in the VenDd group were MRD negative, vs 8% in the DVd group.14 This holds true for different patient subgroups, including those who had 2 or more prior lines of therapy, with 35% of MRD-negative patients in the VenDd group vs only 6% in the DVd group. Similarly, VenDd was associated with higher rates of MRD negativity among patients who were lenalidomide-refractory and who had high-risk genetics.

Patients who were treated with venetoclax had a higher rate of MRD negativity than patients who were not.14 The data show that combining venetoclax with daratumumab and dexamethasone provided greater benefit than bortezomib plus daratumumab and dexamethasone in patients with a t(11;14) translocation.

Download

Update of VenDd vs DVd in t(11;14) R/R MM: PFS (Primary Endpoint)

Sagar Lonial, MD, FACP:
Treatment with VenDd was also associated with a longer median PFS: 46 months with VenDd treatment vs 16 with DVd treatment.14 Likewise, the 12-month PFS rates for patients in the VenDd group compared to the DVd group were 94% and 60%, respectively. The 24-month PFS rate was also higher among patients in the VenDd group, at 77% relative to 40% in the DVd group.

Across the board, the addition of venetoclax to daratumumab and dexamethasone was better than the addition of bortezomib, with a longer median PFS and better benchmark PFS at every year of follow-up.

Download

Update of VenDd vs DVd in t(11;14) R/R MM: OS and PFS by MRD Negativity

Sagar Lonial, MD, FACP:
When assessing PFS by MRD status, among patients who received VenDd, those who were MRD negative had a median PFS of 40 months vs not yet evaluable for patients who were MRD positive.14 The 24- and 33-month PFS rates were also higher in the MRD-negative cohort compared to the MRD-positive cohort. Similarly, for OS by MRD status, although the median has not yet been reached for either MRD subset, the 24- and 33-month PFS rates were also higher in the MRD-negative cohort compared to the MRD-positive cohort. Clearly, the MRD-negative group experienced better outcomes.

Thus, the question for future studies is how to increase the rate of PFS and OS for patients receiving venetoclax who do not achieve MRD negativity.

Download

Update of VenDd vs DVd in t(11;14) R/R MM: Safety Summary

Sagar Lonial, MD, FACP:
In terms of safety, the rates of AEs were relatively similar between the 2 treatment arms.14 Patients in the VenDd group experienced SAEs at a rate of 52.9 events per 100 patient-years, while patients in the DVd group experienced SAEs at a rate of 67.1 events per 100 patient-years.

The percentage of patients experiencing grade 3 or higher AEs and deaths related to AEs were relatively similar as well.

Lastly, the rate of all-cause mortality was also higher in the DVd group than in the VenDd group at 20.8% vs 14.5%, respectively.

Safety of venetoclax combinations for patients with R/R multiple myeloma was a concern based on experience from previous trials.16,17 Fortunately, these data demonstrate that venetoclax plus daratumumab and dexamethasone was not associated with increased AEs in patients with t(11;14) mutations.

Download

Which of the following results was reported in the phase I/II study for patients with R/R multiple myeloma and t(11;14) translocation receiving venetoclax + daratumumab/dexamethasone vs those receiving bortezomib + daratumumab/dexamethasone?

BACK | NEXT