Early SYMPATICO Data Support Ibrutinib-Venetoclax Use in Frontline MCL

The use of ibrutinib (Ibr) and venetoclax (Ven) as first-line treatment can benefit older patients with mantle cell lymphoma (MCL) and younger patients with TP53 mutations, according to a study presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

The phase 3 SYMPATICO study was led by Michael Wang, MD, of the MD Anderson Cancer Center. It showed promising efficacy with high complete response (CR) rates and durable remissions among older patients with treatment-naive (TN) MCL and younger patients who had a TP53 mutation.

 The study included two groups of patients with TN MCL: those aged 65 years and older and younger patients with a TP53 mutation who needed novel and better tolerated treatment options. The study had an open-label safety run-in phase, a randomized phase, and an open-label cohort.

During the treatment period, patients received 560 mg of Ibr and 400 mg of Ven (after ramp-up) once daily for 2 years, then single-agent Ibr 560 mg until disease progression or unacceptable toxicity occurred. The median time spent by patients in the study was 40.5 months, and the median duration of treatment was 24 months (range, 0.6-46.9 months).

The primary end point was CR rate, and key secondary end points included overall response rate (ORR), duration of response, and time to next treatment. Subgroup analyses were performed according to TP53 mutation status and age. Among 78 patients with TN MCL, the CR rate was 69% (95% CI, 58%-79%), and the ORR was 95% (95% CI, 87%-99%).

The most common adverse events (AEs) were diarrhea (49%), fatigue (37%), neutropenia (35%), and COVID-19 infection (32%). The most common AE of grade 3 or higher was neutropenia (29%). Overall, safety was acceptable and trended better among younger patients. The investigators determined that Ibr+Ven treatment is a potential option for older patients with TN MCL or patients of any age with a TP53 mutation.

“Ibrutinib in combination with venetoclax, two oral chemotherapy-free targeted agents, induced good efficacy and [had an acceptable] toxicity profile with durable remission times in older patients with newly diagnosed mantle cell lymphoma or in young patients with TP53 mutations,” Michael Wang, MD, told Blood Cancers Today.