Pooled analysis results from open-label studies for patients with R/R MCL treated with ibrutinib

The results of a pooled analysis were published in the British Journal of Haematology on 18^th August 2017 by Simon Rule, Plymouth University Medical School, UK, and colleagues. The purpose of the pooled analysis was to determine ibrutinib use and impact in Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL).

Patients with R/R MCL (n = 370) were evaluated from three open-label studies; PCYC-1104 (n = 111), SPARK (n = 120), and RAY (n = 139). The median age of patients was 67.5 years and they had received, on average, two previous lines of therapy.

Key Findings:

Efficacy:

• ORR = 66% (20% CR, 46% PR)
• DoR = 18.6 months
• PFS = 12.8 months
• OS = 25.0 months
• Patients who had received only one prior line of therapy had the longest PFS and OS
  • Median PFS and OS not reached
  • 2-year PFS = 57%; 2-year OS = 68%
• Patients treated with ibrutinib at second line achieved highest ORR = 73%; CR = 27%
  • Patients who achieved CR; 2-year PFS = 79% and OS =92%
• Univariate analysis:
  • Patients with blastoid and non-blastoid histology; ORR = 50% and 67.8% and best time to response 2.2 and 2.1 months but DoR, PFS, and OS were significantly shorter in blastoid patients
• Multivariate analysis:
  • Only significant for PFS in one versus more than one prior line of therapy

Safety:

• Grade ≥3 AEs = 71.6%
  • Most frequent AEs = diarrhoea (39.5%), fatigue (34.9%), cough (21.9%)

The results of the pooled analysis study showed that response rates to ibrutinib were high in all subgroups. PFS and OS depended on baseline characteristics although the analysis demonstrated improvement if ibrutinib was used in previous therapy. Patients who achieved CR with ibrutinib showed very high 2-year PFS and OS data. The study provides promising data to support the use of ibrutinib in R/R MCL with a good risk-benefit safety profile.

Abstract:

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease.