Venetoclax is FDA approved for use in certain types of leukemia. It proved to be useful for some leukemia patients with a chromosome 17 P deletion. For the past few years, Venetoclax has been the subject of several studies for use in myeloma. But it has been a bumpy road. During testing several patients died and the FDA, for a time, put a halt to the study. It is still unclear exactly why the deaths happened. But at the same time, studies have shown that Venetoclax has a remarkable ability to target myeloma cells in patients with chromosome 11/14 translocations without this kind of toxicity.
The FDA has not yet approved Venetoclax for use in myeloma. Some doctors are using it off label for their t (11;14) myeloma patients. Many are calling for its approval.
There were a number of abstracts dealing with Venetoclax at ASH 2019. Here is a summary of several of their conclusions.
Mutations and Copy Number Gains of the BCL2 Family Members Mediate Resistance to Venetoclax in Multiple Myeloma Patients
This study recognized that the results of previous study and the shorter overall survival rate (due to the deaths) highlighted the challenges secondary resistance poses and the need to investigate the mechanisms mediating the emerged resistance to Venetoclax.
The study discovered mutations that cause resistance to Venetoclax. The conclusion states that early detection and dynamic monitoring of these abnormalities with early therapeutic interventions targeting these clones may enhance Venetoclax efficacy and improve patient survival.
T (11; 14) and BCL2 Expression are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 BELLINI Study
It was an earlier BELLINI study that had the patient deaths. The study was halted but those who were benefiting from the drug were allowed to continue. This phase 3 study concludes: “ Adding Venetoclax to Bortezomib demonstrates significant efficacy in patients with relapsed refractory multiple myeloma harboring either T (11; 14) or tumor cells expressing high levels of BCL2. The benefit risk profile appears to be favorable in these subsets of patients and additional studies to gain further safety and efficacy information are warranted.”
Phase I/II Study Evaluating the Safety and Efficacy of Venetoclax in Combination with Dexamethasone as Targeted Therapy for Patients with T (11/14) Relapsed/Refractory Multiple Myeloma
This study showed that Venetoclax was efficacious and demonstrated tolerable safety in patients with T (11;14) relapsed refractory multiple myeloma. It’s stated that these results support further investigation Venetoclax combinations in this patient population.
Physical Function, Pain Severity, and Fatigue in Patients With a Relapsed/Refractory Multiple Myeloma: Health Related Quality of Life Results in Patients Receiving Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone
Health related quality of life was comparable in patients receiving Venetoclax in combination with bortezomib and dexamethasone compared to patient receiving bortezomib and dexamethasone alone.
Thank you to our Myeloma Coach ASH 2019 sponsors:
By Vicki Jones