Clinical Trials: Venetoclax for Multiple Myeloma 11;14 Translocation Patients

Multiple myeloma patients who have the 11;14 translocation may want to consider using venetoclax (Venclexta) as a treatment option. While venetoclax isn't yet FDA-approved, it is available to be used in a variety of clinical trials. It is the only truly targeted and effective therapy for a specific genetic mutation in myeloma treatment today. Venetoclax is an oral BCL-2 inhibitor. Dr. Jonathan Kaufman shares how venetoclax works: 

One of the things that we know about cancer cells, every cancer cell and every myeloma cell, is that they are very sick. The cell is sick, and it wants to die. Because there are so many signals within the cancer cell, the cell itself wants to die, but in order for it to turn into cancer, this very sick cell has developed a strategy to prevent itself from dying. It creates or over-expresses or modifies, in some way, all of these anti-death proteins that keep the cell alive. 

There are several anti-death proteins. One of them is the target of venetoclax called BCL-2. There's another one called MCL-1. There's another one called BCL-XL. All of these proteins are there to keep the cell from dying, and they work in a very complicated and coordinated fashion with each other and with similar proteins to keep the cell alive. Almost every myeloma cell is, in some way, dependent on MCL-1 to stay alive. There's currently a lot of clinical investigation, clinical trials, research into drugs that target MCL-1, but they're not really far in development at all. There's really very little clinical data about MCL-1 inhibitors.

BCL-2, in a subset of patients, is the protein that is really important in keeping the cell alive. Venetoclax is a drug that specifically targets BCL-2. The venetoclax basically removes the guardian of the cancer cell and allows the cancer cell to die because that's what it wants to do. It's really amazing technology, in terms of identifying these proteins that sit in this perfect little pocket to stop this protein called BCL-2 from working. 

The three clinical trials below are using venetoclax in three different combinations: 

CANOVA Study

• Phase III study including 244 patients
• Treatment arms: Venetoclax/dex vs. pomalidomide/dex
• Who can join: relapsed or refractory myeloma patients with measurable disease who have the 11;14 translocation. Patients must have had at least two prior lines of therapy using Revlimid (lenalidomide) and a proteasome inhibitor
• Best for: older patients who are not on triplet therapies who have relapsed after common myeloma treatments
• Pros: An all oral treatment
• Find this trial on www.healthtree.org

M15-538 Study

• Phase II study including 120 patients
• Treatment arms: Venetoclaz/carfizomib/dex vs. carfilzomib/dex
• Who can join: relapsed or refractory myeloma patients with measurable disease who have the 11;14 translocation. Patients must have had one prior line of therapy. Patients may not have already had treatment using carfizlomib, dex, venetoclax or other BCL-2 inhibitors
• Best for: Patients with 11;14 relapsing early after using common myeloma treatments
• Pros: Lower chance of developing neuropathy (associated with bortezomib)
• Find this trial on www.healthtree.org

M15-538 Study

• Phase 1/2 study including 104 patients with dose escalation and use in various combination therapies
• Treatments arms: Venetoclax/daratumumab/dex (at 2 dose levels) vs. venetoclax/daratumumab/bortezomib/dex vs. daratumumab/bortezomib/dex
• Who can join: relapsed or refractory myeloma patients with measurable disease who have the 11;14 translocation. Patients must have had one prior line of therapy using an immunomodulator.
• Best for: Patients with 11;14 relapsing early after using common myeloma treatments
• Pros: The use of triple and quad therapies with standard of care myeloma treatments and venetoclax
• Find this trial on www.healthtree.org

For more detailed information about venetoclax, listen to Jonathan Kaufman, MD of Emory University discuss these clinical trials and how venetoclax works.