Long-Term Ibrutinib Follow-up Demonstrates Continued Efficacy in MCL

More than one-quarter of patients with relapsed/refractory mantle cell lymphoma remained progression free and nearly half were alive at 3 years when treated with the BTK inhibitor ibrutinib (Imbruvica).

Simon Rule, MD, PhD

More than one-quarter of patients with relapsed/refractory mantle cell lymphoma (MCL) remained progression free and nearly half were alive at 3 years when treated with the BTK inhibitor ibrutinib (Imbruvica), according to results of a pooled analysis presented at the 2017 ASH Annual Meeting.1

Additionally, patients who were treated with ibrutinib following 1 line of prior therapy experienced the best outcomes.

At 2 and 3 years, 36% (95% CI, 0.31-0.42) and 26% (95% CI, 0.20-0.32) of patients were progression free, respectively. Overall, 53% (95% CI, 0.47-0.58), 45% (95% CI, 0.39-0.50), and 37% (95% CI, 0.25-0.49) of patients were alive at 2, 3, and 5 years, respectively. The median overall survival (OS) was 26.7 months and the complete response (CR) rate was 26.5%.

“Data from this large clinical trial data set with extended follow-up support the early use of ibrutinib in patients with relapsed or refractory mantle cell lymphoma,” Simon Rule, MD, professor of hematology at Plymouth University Medical School, United Kingdom, and lead investigator and presenter of the pooled analysis, said in a press release. “Long-term follow-up for ibrutinib demonstrates, that in addition to efficacy, new onset adverse events decrease over time and are generally less common when patients are treated earlier.”

The analysis included 370 patients who were enrolled in the phase II SPARK, phase III RAY, and phase II PCYC-1104 studies, as well as additional exposure and follow-up of 87 patients across the studies who were enrolled in the long-term CAN3001 access study. The median follow-up was 3.5 years.

Those who were enrolled in SPARK (n = 120), RAY (n = 139), and PCYC-1104 (n = 111) were treated with ibrutinib orally at 560 mg daily once daily until progressive disease or unacceptable toxicity. Across the 3 trials, inclusion and exclusion criteria were similar; however, patients in SPARK were required to have received rituximab (Rituxan) and bortezomib (Velcade) and in RAY to have received prior rituximab.

Those who continued to have a benefit with ibrutinib at the end of the study were eligible to enroll in the phase IIIb open-label CAN3001 study, which provided continued access to ibrutinib. The primary endpoints included investigator-assessed tumor response, progression-free survival (PFS), and OS.

The median duration of follow-up in the pooled set was 41.1 months (95% CI, 37.3-42.5) and the median treatment exposure was 11.1 months (range, 0.03-72.1). A total of 83 and 40 patients were exposed to ibrutinib at ≥3 and ≥4 years, respectively. Of the 87 patients enrolled on CAN3001, 54 (62.1%) remained on ibrutinib. The median number of prior lines of therapy before receiving ibrutinib was 2.

The median overall response rate (ORR) was 69.7%. Additionally, the partial response (PR) rate was 43.2% and the stable disease (SD) rate was 11.6%.

The median PFS overall was 13.0 months. Median PFS was 33.6, 8.4, 46.2, 14.3, and 4.9 months in patients with 1 prior line of therapy, more than 1 prior line of therapy, those who achieved a CR, those who achieved a PR, and those achieved SD, respectively. The median OS was not estimable, 22.5 months, not estimable, 26.2 months, and 10.0 months in those who received 1 prior line of therapy, more than 1 therapy, and those who achieved a CR, PR, and SD, respectively.

Patients with favorable baseline disease characteristics were more likely to remain on ibrutinib for more than 3 years.

Regarding safety, grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 295 patients (79.7%), and new onset events decreased after 1 year. The most common grade 3/4 TEAEs were neutropenia (17%), thrombocytopenia (12.2%), pneumonia (11.9%), anemia (9.5%), atrial fibrillation (5.9%), and hypertension (5.1%). The majority of these AEs were more common during the first year of ibrutinib therapy.

Treatment-emergent serious adverse events (SAEs) occurred in 229 patients (61.9%) and new onset SAEs decreased over time. Cumulative incidence of any major hemorrhage was 7.3% and new onset events decreased after year 1.

“We are proud to have helped so many patients worldwide in their battle against blood cancers such as mantle cell lymphoma with Imbruvica,” Craig Tendler, MD, vice president, late-stage development and global medical affairs for oncology, Janssen Research and Development, said in a press release. “Building on [the] oral presentation, we’re pleased that the early clinical benefit first seen with Imbruvica in patients with relapsed/refractory MCL has been maintained with longer follow-up, and enhanced for those patients treated earlier in their disease course.”

The FDA approved ibrutinib in November 2013 as a treatment for patients with MCL who have received at least 1 prior therapy. The decision was based on the initial findings from the PCYC-1104 trial, in which ibrutinib demonstrated an ORR of 68%, including a CR rate of 21%.2


  1. Rule S, Dreyling M, Goy A, et al. Median 3.5-year follow-up of ibrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: a pooled analysis. In: Proceedings from the 2017 ASH Annual Meeting; December 9-12, 2017; Atlanta, Georgia. Abstract 151.
  2. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507-516. doi: 10.1056/NEJMoa1306220.