FDA Warns of Risks Associated with Venetoclax Use in Multiple Myeloma


Interim phase 3 trial results showed an increased risk of death for patients receiving venetoclax for multiple myeloma.

Officials with the FDA are warning health care professionals, oncology clinical investigators, and patients about heighted risks associated with the use of venetoclax (Venclexta) for the treatment of multiple myeloma, according to a drug safety alert.

Following a review of data from the ongoing phase 3 BELLINI trial, the FDA has placed a partial clinical hold on all clinical trials evaluating venetoclax for multiple myeloma. The BELLINI trial is evaluating the use of venetoclax combined with bortezomib and dexamethasone in patients with multiple myeloma.

According to the agency, interim trial results showed an increased risk of death for patients receiving venetoclax compared with the control group. The warning does not apply to patients taking venetoclax for an approved indication, such as in chronic lymphocytic leukemia or acute myeloid leukemia.

The FDA has suspended enrollment in other ongoing multiple myeloma trials for venetoclax, as well. Patients who are receiving clinical benefit can continue treatment in these trials after they reconsent.

In the BELLINI trial, 291 patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy were administered bortezomib and low-dose dexamethasone with or without venetoclax. At the interim analysis of overall survival, there were 41 out of 194 deaths on the venetoclax-containing investigational arm, of which 6.7% were treatment emergent, according to AbbVie. Of the 13 treatment-emergent deaths, 8 were attributed by the investigator to an event of infection and more than half were in the setting of refractory or progressive disease. In the placebo arm, 11 out of 97 deaths were observed, among which 1 was treatment emergent.

The hazard ratio of the venetoclax-containing investigational arm compared with the placebo arm was 2.03% (95% CI: 1.04,3.94), increasing the relative risk of death by approximately 2-fold compared with the placebo arm, according to the FDA.

Additionally, the median progression-free survival in the study was 22.4 months for the venetoclax arm and 11.5 months for the placebo arm, meeting the trial’s primary endpoint. The overall response rate was 82% in the investigational arm compared with 68% in the placebo arm, according to the data.

The incidence of severe grade 3 to 5 toxicity and serious adverse events was similar between the 2 arms. Common non-disease progression causes of death identified in the venetoclax arm were sepsis, pneumonia, and cardiac arrest.

“We are committed to patient safety and are thoroughly analyzing the results observed in the BELLINI trial,” Michael Severino, MD, vice chairman and president of AbbVie, said in a statement. “We will continue working with the FDA and worldwide regulatory agencies to determine appropriate next steps for the multiple myeloma program. We will continue to further the research and development of venetoclax and other therapies with the potential to transform the standards of care in blood cancers.”

Venetoclax is being developed by AbbVie and Roche.


FDA warns about the risks associated with investigational use of Venclexta in multiple myeloma [FDA safety alert]. FDA. https://www.fda.gov/Drugs/DrugSafety/ucm634120.htm. Accessed March 22, 2019.

AbbVie Provides Update on Venclexta/Venclyxto (venetoclax) Multiple Myeloma Program [news release]. AbbVie. https://news.abbvie.com/news/press-releases/abbvie-provides-update-on-venclextavenclyxto-venetoclax-multiple-myeloma-program.htm. Accessed March 22, 2019.

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