First-line acotinib/acalabrutinib plus chemoimmunotherapy induces meaningful survival benefit in MCL

Acalabrutinib plus bendamustine (Bendamustine; B Endeka) and rituximab (Rituxan; Rituxan), a standard-of-care chemoimmunotherapy regimen, provides a progression-free survival (PFS) benefit compared with standard-of-care alone in adult patients with untreated mantle cell lymphoma (MCL).

High-level data to be released demonstrate statistically significant and clinically meaningful improvements in PFS when adding acotinib to bendamustine and rituximab. Additionally, patients treated with the study arm showed a positive trend in overall survival (OS) compared with the standard treatment arm alone, although OS results were not yet mature at the time of analysis. Safety results were consistent with the known safety profile of acotinib, and no new safety signals were reported.

These positive PFS results fromthe phase 3 ECHO trial may provide a new standard of care for MCL patients. Incorporating acotinib into the first-line MCL setting will give more patients the opportunity to benefit from this drug's strong efficacy and strong safety profile. ECHO is an ongoing double-blind, placebo-controlled, multicenter study enrolling patients with MCL who are at least 65 years of age and previously untreated (n=598). Eligible patients were required to have pathologically confirmed chromosomal translocation t(11;14)(q13;q32) and/or cyclin D1 overexpression, an ECOG performance status of 2 or less, and use an effective method of contraception during the study within 6 months after the last dose of bendamustine, and/or within 12 months after the last dose of rituximab.

After enrollment, patients were randomly assigned1:1 to receive oral acotinib or placebo twice daily during a 28-day treatment cycle. Both groups received bendamustine on days 1 and 2 of each cycle and rituximab on day 1. After 6 cycles of acotinib or placebo, patients received maintenance therapy with acotinib or placebo plus rituximab for 2 years and then received acotinib or placebo alone until disease progression. The primary endpoint of the study was PFS according to the Lugano classification of non-Hodgkin lymphoma. Secondary endpoints included overall response rate, OS, duration of response, and time to response.

Acotinib inIn October 2017, it received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with MCL who have received at least one prior treatment. The drug was also approved by the FDA in November 2019 to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Acotinib has been approved for the treatment of CLL in the European Union (EU), as well as relapsed/refractory CLL and SLL in China and Japan; the drug has not yet received approval for MCL in Japan or the EU.

These impactful results in mantle cell lymphoma demonstrate that the introduction of acotinib into first-line therapy can significantly delay disease progression and show for the first time the potential to extend survival,The improvement in PFS is important as is the differentiated safety profile of acotinib.