Share on Facebook
Share on Twitter
Share on LinkedIn
Share by Email
Print
Adding venetoclax to treatment with ibrutinib can improve outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL), according to research presented at the ASH Annual Meeting 2023.
The combination improved progression-free survival (PFS), complete response (CR) rate, and time to next treatment, when compared to ibrutinib alone in the phase 3 SYMPATICO trial.
“In my personal opinion, in the countries where ibrutinib is indicated to treat mantle cell lymphoma, this combination is a new standard therapy for relapsed/refractory mantle cell lymphoma,” said Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, when presenting these results at the meeting.
The SYMPATICO trial (ClinicalTrials.gov Identifier: NCT03112174) included 267 patients relapsed or refractory MCL. The patients had received 1 to 5 prior lines of therapy, including at least 1 regimen containing anti-CD20 therapy.
The patients were randomly assigned to receive ibrutinib plus venetoclax (n=134) or ibrutinib plus placebo (n=133). Baseline characteristics were generally well balanced between the arms, but patients in the combination arm were older and more likely to have high-risk disease.
Ibrutinib was given at 560 mg daily, and venetoclax was given on a 5-week ramp up to 400 mg. Patients received their assigned treatment for 2 years and then received single-agent ibrutinib at 560 mg daily until disease progression or unacceptable toxicity.
The median treatment duration was 22.2 months in the combination arm and 17.7 months in the ibrutinib-alone arm. The median follow-up was 51.2 months.
The median PFS by investigator assessment was 31.9 months with ibrutinib-venetoclax and 22.1 months with ibrutinib alone (hazard ratio [HR], 0.65; 95% CI, 0.47-0.88; P =.0052).
The median time to next treatment was not reached in the ibrutinib-venetoclax arm and was 35.4 months in the ibrutinib-alone arm (HR, 0.60; 95% CI, 0.40-0.89; P =.0096).
The overall response rate was 82% in the combination arm and 84% with ibrutinib alone (P =.1279). The CR rate was 54% and 32%, respectively (P =.0004). The median duration of response was 42.1 months and 27.6 months, respectively.
The median overall survival was 44.9 months with ibrutinib plus venetoclax and 38.6 months with ibrutinib alone (HR, 0.85, 95% CI, 0.62-1.19; P =.3465).
Grade 3 or higher adverse events (AEs) occurred in 84% of patients in the ibrutinib-venetoclax arm and 76% of those in the ibrutinib-alone arm. Serious AEs occurred in 60% of patients in each arm.
The most frequent grade 3 or higher AEs (in the ibrutinib-venetoclax and ibrutinib-alone arms, respectively), were neutropenia (31% vs 11%), pneumonia (13% vs 11%), thrombocytopenia (13% vs 8%), anemia (10% vs 3%), diarrhea (8% vs 2%), leukopenia (7% vs 0%), worsening of MCL without meeting criteria for disease progression (7% vs 12%), atrial fibrillation (5% in both arms), COVID-19 (5% vs 1%), and hypertension (4% vs 9%).
There were 22 fatal AEs in the ibrutinib-venetoclax arm and 18 in the ibrutinib-alone arm. Per investigator opinion, there were 3 ibrutinib-related deaths in the combination arm and 2 in the monotherapy arm. There were no venetoclax-related deaths, but there was 1 placebo-related death.
There were 10 COVID-19-related deaths in each arm, which had “no meaningful impact” on the PFS or OS benefit with ibrutinib and venetoclax, according to Dr Wang.
Disclosures: This research was supported by Pharmacyclics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Wang M, Jurczak W, Trněný M, et al. Ibrutinib Combined with venetoclax in patients with relapsed/refractory mantle cell lymphoma: Primary analysis results from the randomized phase 3 Sympatico study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract LBA-2.
This article originally appeared on Cancer Therapy Advisor
