Journal Article

Concurrent ibrutinib plus venetoclax in relapsed/refractory mantle cell lymphoma: the safety run-in of the phase 3 SYMPATICO study

Ramchandren, Radhakrishnan, Neuenburg, Jutta K., Eckert, Karl, Karlin, Lionel, Wu, Ka Lung, Lee, Yihua, Jurczak, Wojciech, Eliadis, Paul, Wang, Michael, Chong, Geoffrey, Tam, Constantine S., Collins, Graham P., Peyrade, Frédéric, Bishton, Mark, Chen, Robert

2021

Overview

Ibrutinib plus venetoclax, given with an ibrutinib lead-in, has shown encouraging clinical activity in early phase studies in mantle cell lymphoma (MCL). The ongoing phase 3 SYMPATICO study evaluates the safety and efficacy of concurrently administered, once-daily, all-oral ibrutinib plus venetoclax in patients with relapsed/refractory MCL. A safety run-in (SRI) cohort was conducted to inform whether an ibrutinib lead-in should be implemented for the randomized portion. Patients received concurrent ibrutinib 560 mg continuously plus venetoclax in a 5-week ramp-up to venetoclax 400 mg for up to 2 years. The primary endpoint was occurrence of tumor lysis syndrome (TLS) and dose-limiting toxicities (DLTs). The SRI cohort enrolled 21 patients; six and 15 were in low- or increased-risk categories for TLS, respectively. During the 5-week venetoclax ramp-up, three patients had DLTs, and one patient at increased risk for TLS had a laboratory TLS; no additional TLS events occurred during follow-up. With a median follow-up of 31 months, the overall response rate was 81% (17/21); 62% (13/21) of patients had a complete response. SRI data informed that the randomized portion should proceed with concurrent ibrutinib plus venetoclax, with no ibrutinib lead-in. Ibrutinib plus venetoclax demonstrated promising efficacy; no new safety signals were observed. Trial registration : ClinicalTrials.gov, NCT03112174. Registered 13 April 2017, https://clinicaltrials.gov/ct2/show/NCT03112174 .

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Antimitotic agents / Antineoplastic agents / Apoptosis / Blood / Blood cancer / Bone marrow / Cancer Research / Cardiac arrhythmia / Creatinine / Development and progression / Hematological cancers/lymphomas / Hematology / Ibrutinib / Inhibitor drugs / Laboratories / Leukemia / Lymphoma / Lysis / Mantle cell lymphoma / Medicine / Medicine & Public Health / Neutropenia / Non-Hodgkin's lymphomas / Oncology / Patients / Potassium / Rapid Communication / Safety / Safety and security measures / Small molecule agents/kinase inhibitors / Targeted cancer therapy / Tumors / Venetoclax