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

The 59^th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on 9–12 December 2017. On December 9^th, 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