The primary endpoint of the phase 3 SELENE trial was not met after a median of 84 months of follow-up, with no significant difference in progression-free survival (PFS) among patients with relapsed/refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL) treated with ibrutinib or placebo plus chemoimmunotherapy (CIT).
These findings, which were presented at the International Conference on Malignant Lymphoma 2023, were consistent across all major subgroups, including background therapy, prior lines of therapy, disease status, and histology.
The double-blind, phase 3 SELENE trial (ClinicalTrials.gov identifier: NCT01974440) randomly assigned 403 patients with relapsed/refractory FL or MZL to receive either ibrutinib or placebo in addition to BR or R-CHOP. All patients had received at least 1 prior treatment with an anti-CD20-based regimen. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR), duration of response (DOR), and safety.
At baseline, the median age was 59, with 36% of patients aged 65 or older. There were 13.9% of patients in each treatment group with MZL. The median number of prior lines of treatment was 1 (range, 1-10). There were 23% of patients who were refractory to their last treatment. The majority of patients received BR in the trial at 90%.
The median PFS was 40.5 months with ibrutinib plus CIT compared with 23.8 months with placebo plus CIT; however, this was not statistically significant (hazard ratio [HR], 0.81; 95% CI, 0.63-1.04; P =.0922).
The median OS was not yet reached in either arm. The 7-year OS was 67.4% with ibrutinib compared with 68.3% with placebo. Among patients with MZL, the rates were 76.6% and 68.5% with ibrutinib or placebo, respectively (HR, 0.69; 95% CI, 0.24-2.00; P =0.4964).
The response rates to ibrutinib or placebo were similar, with an ORR Of 91.6% and 90.5%, respectively, and CR rates of 55.0% and 50.2%, respectively. Among patients with MZL, the ORR was 89.3% with ibrutinib and 82.1% with placebo. The CR rates were 64.3% and 60.7%, respectively.
However, the median DOR was 44.3 months with ibrutinib compared with 21.7 months with placebo. Among patients with MZL, the median DOR was not yet reached in the ibrutinib group compared with 89.2 months in the placebo group.
The rates of serious treatment-related treatment-emergent adverse events (TEAEs) was 34.8% with ibrutinib and 18.1% with placebo. The most common grade 3 or higher adverse events were thrombocytopenia, neutropenia, anemia, and diarrhea. TEAEs resulted in a dose reduction among 20.4% and 10.6% of patients in the ibrutinib and placebo groups, respectively, and discontinuation of the study drug among 30.8% and 18.6%, respectively.
Of the TEAEs of special interest, 13.9% of patients treated with ibrutinib experienced arthralgia compared with 18.1% in the placebo arm. Rates of hypertension were similar at 9.5% in each treatment arm. Atrial fibrillation occurred more frequently in the ibrutinib group at 6.5% compared with 2.0% in the placebo group.
“In the SELENE study, the addition of ibrutinib to CIT in patients with relapsed/refractory FL or MZL did not significantly improve PFS,” the authors concluded. “Further analyses are needed to define specific FL/MZL subgroups that could potentially benefit from extended treatment with ibrutinib following CIT.”
Disclosures: This research was supported by Janssen Pharmaceuticals, Inc. and Pharmacyclics LLC. Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Nastoupil LJ, Hess G, Pavlovsky MA, et al. Ibrutinib plus BR or R-CHOP in previously treated patients with follicular or marginal zone lymphoma: the phase 3 SELENE study. ICML 2023. June 13-17, 2023. Abstract LBA2.