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Ibrutinib-venetoclax combination shows superior progression-free survival and higher complete response rate than ibrutinib and placebo

: Ibrutinib Combined with Venetoclax in Patients with Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis Results from the Randomized Phase 3 Sympatico Study

(SAN DIEGO, Dec. 12, 2023) – Patients with relapsed or refractory mantle cell lymphoma (MCL) who received ibrutinib in combination with venetoclax experienced significantly better rates of progression-free survival compared with patients who received ibrutinib and placebo in an international phase III trial being reported during the 65th ÎÚÑ»´«Ã½ (ASH) Annual Meeting and Exposition. Researchers say the findings suggest that ibrutinib and venetoclax, which have different modes of action, work synergistically, resulting in a better response than either drug alone. 

“Ibrutinib plus venetoclax has been shown to be very effective, safe, and well tolerated, and could benefit many patients with relapsed MCL,” said Michael Wang, MD, Puddin Clarke Endowed Professor at The University of Texas MD Anderson Cancer Center, the study’s lead author and principal investigator. “This combination should be a new standard therapy for relapsed/refractory MCL patients in countries ibrutinib is approved for MCL.”

MCL is a rare non-Hodgkin lymphoma, a cancer of white blood cells, that is most common in older adults. Patients affected with this cancer often have swollen lymph nodes, enlarged spleen, and abnormal blood counts due to damage to the bone marrow by the cancer. After frontline therapies, a majority of patients see this cancer relapse after initially responding to treatment. Ibrutinib is currently approved for relapsed MCL in many countries but was withdrawn for MCL in the U.S. after a confirmatory trial met its primary progression-free survival endpoint but failed to meet its secondary overall survival endpoint.  

Ibrutinib and venetoclax are oral cancer drugs that are designed to affect different biochemical pathways. Ibrutinib targets Bruton tyrosine kinase (BTK), an enzyme involved in cell signaling, whereas venetoclax inhibits BCL2 proteins, which are involved in cell survival and growth. 

For the phase III trial, researchers enrolled 267 patients with MCL whose cancer had not responded to previous treatments or had returned after an initial response. After a median follow-up of 51 months, the results showed significantly better outcomes with the ibrutinib-venetoclax combination. The median progression-free survival, the trial’s primary endpoint, was significantly longer with 31.9 months in the combination group compared with 22.1 months in the placebo group. 

Treatment with ibrutinib and venetoclax was also associated with a significantly better rate of complete response (CR, or the eradication of cancer as measured with standard imaging methods), which was achieved in 54% of those assigned to the combination therapy and 32% of those in the placebo group. 

“The combination was synergistic, with a CR rate that is higher than the additive CR rate of the two drugs,” said Dr. Wang. “This is a clinical benefit for the patient and a landmark achievement for the treatment of MCL.”

The benefits of the combination therapy were consistent across subgroups of patients with high-risk features. The overall survival rate was numerically higher in the group that received the combination therapy, but the difference was not statistically significant. 

Adverse events were more common among patients who received the combination therapy, with the most frequent events including low white blood cell count, low platelet count, pneumonia, and anemia. About 60% of participants in both study arms experienced adverse events that were considered serious. Adverse events of grade three or higher were more common among those receiving the combination therapy, 84% of whom experienced such events compared to 76% in the control arm. 

The study was funded by AbbVie, maker of ibrutinib.  

Michael Wang, MD, of MD Anderson Cancer Center, will discuss this study in the Late-Breaking Abstracts Session on Tuesday, Dec. 12, 2023, at 9:00 a.m. Pacific time in Hall A (San Diego Convention Center).

The ÎÚÑ»´«Ã½ (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology.

ASH’s flagship journal, Blood () is the most cited peer-reviewed publication in the field, and Blood Advances () is an open-access, online journal that publishes more peer-reviewed hematology research than any other academic journal worldwide. Two new journals will be joining the Blood Journals portfolio in 2024, Blood Neoplasia () and Blood Vessels, Thrombosis & Hemostasis ().

Contact:  
Melissa McGue, ASH, [email protected]
Kira Sampson, ASH, [email protected] 
Brianne Cannon, FleishmanHillard, [email protected]