ASH 2023: Using Venetoclax with 11;14 Myeloma Patients

Updated data and expert perspectives on the potential role of venetoclax (Venclexta) in myeloma patients with 11;14 genetic translocation was an important and timely topic at ASH 2023.  

Translocation 11:14, t(11;14) is the most common genetic abnormality in myeloma occurring in approximately 15-20% of patients. 

Venetoclax is a potent, oral BCL2 inhibitor treatment that is FDA-approved for use in chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and is actively being investigated for use in multiple myeloma. 

Although not approved by the FDA for multiple myeloma treatment at this time, venetoclax is currently available to many patients based on its designation in the most recent, National Comprehensive Cancer Network (NCCN) guidelines. 

“Venetoclax with dexamethasone with or without daratumumab or a proteasome inhibitor only for t(11;14) patients” is designated by the NCCN guidelines as “Useful in Certain Circumstances” for relapsed/ refractory patients after 1-3 prior therapies. 

The highly anticipated, but somewhat disappointing results of the CANOVA study were presented on September 29^th, 2023, at the International Myeloma Society meeting. 

This phase 3, randomized study compared venetoclax-dexamethasone vs. pomalidomide-dexamethasone in t(11;14) relapsed/refractory myeloma.  

Although patients in the venetoclax group had numerically longer progression-free survival, the difference was not statistically significant, and the primary endpoint was not met.  

There has been ongoing discussion among the experts regarding the limitations of the CANOVA study design and encouraging post-hoc analysis. 

The designation of venetoclax in the NCCN guidelines has not changed since the release of the CANOVA data. 

What do myeloma experts think about the use of venetoclax for today’s myeloma pts with t(11;14)?

With the CANOVA results released less than 3 months prior to ASH, it is helpful to understand how myeloma experts have processed the totality of the science and their clinical experience to inform their current perspectives regarding venetoclax. 

During the ASH 2023 “Beyond the Guidelines” symposium sponsored by Research to Practice on December 9^th, results were presented from a November 2023 poll of 20 highly distinguished myeloma experts on their response to a variety of treatment scenarios. Here are the results regarding their use of venetoclax. 

Based on these polls and other presentations and research presented at ASH, it appears that many experts believe that venetoclax remains an important treatment option for relapsed/refractory myeloma patients with t(11;14).

Updated Data on Venetoclax in Combination Therapy

At relapse, t(11;14) patients and their doctors may be considering, which is a better treatment option, venetoclax or Velcade (bortezomib) in combination with daratumumab and dexamethasone? 

Data from Abstract 338 presented at ASH on December 9th by Nizar Bahlis, MD, is useful in determining the comparative efficacy and safety of these two options.

In this study, patients were randomized into three treatment groups: Venetoclax 400mg or 800mg plus daratumumab (dara) and dexamethasone (dex) or Velcade plus dara and dex.  

Highlights of the findings are noted below.

In easy-to-understand language, in this study, the t(11;14) patients that received venetoclax plus daratumumab and dexamethasone had significantly longer remissions and deeper responses with a manageable safety profile vs. those that received Velcade (bortezomib) plus dara and dex.

Considerations for Myeloma Patients

Based on the totality of data at this time, expert opinion, and ongoing designation in the NCCN guidelines, it appears that venetoclax continues to be a useful treatment option for t(11;14) relapsed/ refractory myeloma patients. 

Dr. Bahlis noted in his presentation that although t(11;14) has been traditionally considered standard risk, there is some recent evidence to suggest that it may be intermediate risk.

With this in mind, as an 11:14 patient, I am further motivated to stay informed on the evolving data and stay adherent to my treatment plan that has been developed by a leading myeloma expert.   

Considering the complexity and rapidly evolving nature of myeloma, we recommend that all myeloma patients consult with a myeloma expert. You can find one here: HealthTree Specialist Directory

For more information about venetoclax, you can refer to this link on HealthTree University.

As myeloma patients and partners our hope for healthy and fulfilling lives is further justified by the robust data presented at ASH 2023.

We can all stay educated, connected, and empowered, and accelerate the arrival of our future cures through HealthTree programs.

ASH 2023 Resources

Would you like to watch ASH 2023 myeloma research interviews from the investigators themselves? Click "ASH 2023" here: HealthTree University Conference Coverage

To read other ASH 2023 articles, click here: HealthTree 2023 ASH Articles