Researchers find powerful combo weapon against aggressive lymphoma

The targeted therapy combination of ibrutinib and venetoclax significantly improved progression-free survival (PFS) and achieved an overall remission rate in 82% of patients with relapsed/refractory mantle cell lymphoma (MCL), according to researchers at The University of Texas MD Anderson Cancer Center. Results from the Phase III SYMPATICO trial were presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

At a median follow-up of 51.2 months, median PFS was 31.9 months with the combination compared to 22.1 months with ibrutinib plus placebo. PFS benefits were consistent across patient subgroups, including those with blastoid-variant or TP53-mutated MCL. On the combination arm, 54% of patients achieved a complete remission compared to 32% on the placebo arm, a significant improvement.

We are very encouraged by the data from this trial and for our patients to have achieved remissions using this targeted therapy. This combination allowed us to attack the cancer cells in two ways, which made it harder for the tumor to find resistance."

Michael Wang, M.D., principal investigator, professor of Lymphoma & Myeloma

This international, multi-center trial evaluated ibrutinib, a BTK inhibitor, paired with venetoclax, a BCL-2 inhibitor; the two work together to attack MCL cells. MCL is a rare type of non-Hodgkin lymphoma with about 4,000 new cases diagnosed each year in the U.S. Often is diagnosed at stage IV, MCL has an aggressive disease course. According to Wang, MCL is becoming more common as the population ages.

The trial enrolled 267 adults with relapsed/refractory MCL who had previously received at least one prior line of therapy. Patients were randomly assigned to receive ibrutinib and venetoclax or ibrutinib and placebo.

Side effects were manageable and consistent with previous studies. Grade 3 or higher adverse events occurred in 84% of patients treated with the combination and 76% of those on the placebo arm. The most common side effect experienced was neutropenia.

"I am encouraged by our findings as we work to identify effective, targeted, chemo-free treatment options for patients with MCL," Wang said. "We look forward to longer follow-up data from this trial to determine the best therapeutic approach for these patients. This is a milestone achievement for our patients with MCL."

The trial was supported by AbbVie.