MCL

ASH 2017 | Pooled analysis results of ibrutinib therapy in R/R MCL patients for a median of 3.5 years

The 59th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on 9–12 December 2017. On December 9th, an oral abstract session was held on “Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Mantle Cell Lymphoma, New Therapies”. This session was moderated by Jonathon B Cohen, Emory University - Winship Cancer Institute and Craig A. Portell, University of Virginia.

Abstract #151 was presented during this session, titled “Median 3.5-Year Follow-up of Ibrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis” by Simon Rule, Plymouth University Medical School, UK, and colleagues. This article is based on data presented at the live session, which may supersede information in the pre-published ASH Abstract.

The analysis showed 370 patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) who received one (n = 99) or more (n = 271) prior lines of ibrutinib therapy across three studies (SPARK, RAY and PCYC-1104). The authors noted that patients who had been treated with ibrutinib at first relapse or progression had better outcomes.

Study Highlights
  • Overall, 370 patients were enrolled in this pooled analysis CAN3001 (NCT01804686):
    • 115 patients (31.1%) were treated with ibrutinib for ≥ 2 years: 32 of them were treated for 2 to > 3 years (27.8%), 43 patients were treated for 3 to > 4 years and 40 patients for ≥ 4 years (34.8%)
    • Median ibrutinib exposure = 46.3 months (28.8–72.1)
  • Patients received 560 mg ibrutinib once daily with a median follow-up: 41.1 months (95% CI, 37.3–42.5)
  • Median PFS overall: 13.0 (95% CI, 8.4–16.8) months
  • Median OS overall: 26.7 (95% CI, 22.5–38.4) months
  • Overall Response Rates (ORR) by best response:
    • ORR in all patients: 69.7%, 26.5 % achieved Complete Response (CR), 43.2% received Partial Response (PR)
    • ORR in patients with 1 prior line of therapy: 77.8%, CR: 36.4%, PR: 41.4%
    • ORR in patients with > 1 prior line of therapy: 66.8%, CR: 22.9%, PR: 43.9%
  • Duration of Response (DOR) by best response and line of therapy
    • DOR in all patients: 22.2 (95%CI, 16.5–28.8) months, CR: 55.7% (95% CI, 55.7–NE), PR: 10.4% (95% CI, 7.7–14.9)
    • DOR in patients with 1 prior line of therapy: 34.4 (95% CI, 23.1–NE) months, CR: 55.7 % (95% CI, 33.1–NE), PR: 22.1% (95% CI, 10.6–34.4)
    • DOR in patients with > 1 prior line of therapy: 16.0 (95% CI, 12.9–23.5) months, CR: NE (95%CI, 40.7–NE), PR: 8.5 (6.2–12.1)
  • 2-year PFS and OS for patients who had received only 1 prior line of therapy
    • 2 years PFS: 57% (95% CI, 0.31–0.42)
    • 2 years OS: 68% (95% CI, 0.47–0.58)
Safety
  • Treatment-emergent adverse events (TEAEs) grade ≥ 3 = 79.7% of patients
  • Most common TEAEs: neutropenia 17.0%, thrombocytopenia 12.2%, pneumonia 11.9%
  • Secondary malignancies: 9.7%, mostly non-melanoma skin cancer
  • The speaker commented on atrial fibrillation (AF) occurring in 5.1% of patients stating that patients in the study had significant cardiac risk factors including a history of AF. He added that the majority of these patients did not have a recurrence of AF or arrhythmia and that bleeding and AF was managed so that only a few (<2%) required a dose reduction or treatment discontinuation
References
  1. Rule S. et al. Median 3.5-Year Follow-up of Ibrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis. Oral Abstract #151: ASH 59th Annual Meeting and Exposition, December 2017, Atlanta, GA.