Ibrutinib (ibr) is a first-in-class oral inhibitor of Bruton’s tyrosine kinase approved for relapsed/refractory (R/R) mantle-cell lymphoma (MCL). The results of a pooled analysis of 370 patients with R/R MCL treated with ibr in the SPARK, RAY, and PCYC-1104 studies were previously reported (median follow-up, 24 months).1 At ASH 2017, the authors presented median 3.5-year follow-up in these patients, including additional exposure and follow-up of 87 patients across the 3 studies who enrolled in the long-term access study, CAN3001.2
Patients enrolled in SPARK, RAY, and PCYC-1104 received ibr 560 mg orally once daily until progressive disease or unacceptable toxicity. Study inclusion and exclusion criteria were similar, except that patients in SPARK were required to have received both rituximab and bortezomib, and in RAY, prior rituximab. Patients who continued to benefit from ibr therapy at the end of the study were eligible to enroll in CAN3001, an open-label phase 3b study providing continued access to ibr. The pooled analysis presented at ASH 2017 was limited to patients receiving ibr therapy, excluding crossover patients. Investigator-assessed tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated. Of 370 patients, 111 were enrolled in PCYC-1104, 120 in SPARK, and 139 in RAY; 87 of the 370 patients subsequently enrolled in CAN3001. The median duration of follow-up in the pooled data set was 41 months, with a median treatment exposure of 11 months.
At 2 and 3 years, respectively, 36% and 26% of patients were progression-free, and the median PFS was 13.0 months. Median PFS in patients with 1 prior line of therapy was 33.6 (19.4-42.1) months, and in patients achieving complete response (CR) was 46.2 (42.1-not estimable) months. Overall, 53%, 45%, and 37% of patients were alive at 2, 3, and 5 years, respectively. Median OS was 26.7 months.
Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 295 (79.7%) patients, with the new-onset events decreasing after year 1 (67.8%, 47.8%, 34.8%, 36.1%, and 20.0% for years 1, 2, 3, 4, and >4, respectively). The most common (incidence ≥5%) grade ≥3 TEAEs were neutropenia (17.0%), thrombocytopenia (12.2%), pneumonia (11.9%), anemia (9.5%), atrial fibrillation (5.9%), and hypertension (5.1%). Most of these were more common during the first year of ibr treatment.
The authors concluded that in this pooled analysis of ibr-treated patients with R/R MCL with a median 3.5 years of follow-up, more than a quarter of patients remained progression-free and nearly half were alive at 3 years. Clinical outcomes were best for patients who achieved CR and those who were treated with ibr at first relapse/progression.
1. Rule S, et al. Br J Haematol. 2017;179:430-438.
2. Rule S, et al. ASH 2017. Abstract 151.