Among patients with relapsed or refractory mantle cell lymphoma (MCL), concurrent ibrutinib and venetoclax may yield a high overall response rate (ORR) with no unexpected safety signals, according to research published in the Journal of Hematology & Oncology.

The advent of targeted therapies including ibrutinib has greatly improved outcomes among patients with relapsed or refractory MCL. There is, however, a need for effective therapy combinations that prolong progression-free survival (PFS) in this patient population.

Ibrutinib is approved in the United States for treating patients who have progressed on at least 1 prior therapy line, yielding ORRs of up to 77%. Venetoclax, similarly, has shown promise in phase 1 study of relapsed or refractory MCL, demonstrating an ORR of 75%.

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For the randomized phase 3 SYMPATICO study ( Identifier: NCT03112174), researchers are evaluating the safety and efficacy of combination ibrutinib and venetoclax among patients with relapsed or refractory MCL. For the present paper, the authors aimed to determine the safety of this combination without lead-in, hypothesizing that safety run-in (SRI) results might help to inform treatment dosing.

Overall, 21 patients were enrolled in this study. The median age was 68 years, 62% of patients were male sex, 6 patients were at low risk of tumor lysis syndrome (TLS), and 15 patients were at increased risk of TLS. The median number of prior therapy lines was 2 regardless of TLS risk status. All patients received ibrutinib 560 mg concurrently with a 5-week ramp-up to venetoclax 400 mg.

The overall median follow-up was 31 months. During the venetoclax ramp-up period, 3 patients had dose-limiting toxicities, with 1 patient in the higher TLS-risk group developing TLS. The overall response rate was 81%, with a complete response rate of 62%.

The authors noted that no new safety signals were observed. The most common grade 3-4 adverse events were diarrhea (7%), infection (7%), and neutropenia (7%).

“In conclusion, SYMPATICO SRI results demonstrate that ibrutinib plus venetoclax was well tolerated without an ibrutinib lead-in,” the authors wrote. “The randomized portion of the SYMPATICO study is evaluating ibrutinib plus venetoclax versus ibrutinib plus placebo in patients with relapsed/refractory MCL.”

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Wang M, Ramchandren R, Chen R, et al. Concurrent ibrutinib plus venetoclax in relapsed/refractory mantle cell lymphoma: the safety run-in of the phase 3 SYMPATICO study. J Hematol Oncol. 2021;14(1):179. doi:10.1186/s13045-021-01188-x