ORLANDO – Ibrutinib is superior to temsirolimus for progression-free survival and overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL) and has preferable tolerability, according to a phase 3, international, randomized, open-label, multicenter study.1
MCL patients typically achieve only short-term remissions with conventional therapies, so the positive results seen with Imbruvica in this phase 3 trial are particularly striking,” said lead investigator Simon Rule, MD, consultant hematologist and head of the lymphoma service at Derriford Hospital in Plymouth, United Kingdom.2
For the RAY trial, researchers enrolled 280 patients with relapsed or refractory MCL. Participants were randomly assigned to receive ibrutinib 560 mg orally daily or temsirolimus 175 mg intravenously on days 1, 8, and 15 of cycle 1, followed by 75 mg on days 1, 8, and 15 of subsequent 3-week cycles, until unacceptable toxicity or disease progression.
Results showed that the median progression-free survival with ibrutinib was 14.6 months compared with 6.2 months with temsirolimus after a median follow-up of 20 months, which corresponds to a 57% reduction in the risk of disease progression or death (HR, 0.43; 95% CI, 0.32 – 0.58; P < .0001).
In addition, ibrutinib treatment was associated with an overall response rate of 72% vs 40% in the temsirolimus arm (difference, 31.5%; 95% CI, 20.1 – 42.5; P < .0001). Of those in the ibrutinib arm, 19% achieved a complete response while only 1% of those who received temsirolimus achieved a complete response. Median overall survival has not yet been reached with ibrutinib compared with 21.3 months with temsirolimus (HR, 0.76; 95% CI, 0.53 – 1.09)
In regard to safety, the most common ibrutinib-associated adverse events were diarrhea, cough, and fatigue, with the most common hematologic toxicities being thrombocytopenia, anemia, and neutropenia. A total of 7% and 26% of patients in the ibrutinib and temsirolimus arms, respectively, discontinued treatment as a result of adverse events.
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“As clinicians, we strive to ensure our patients receive safe and effective treatment options. The RAY data show Imbruvica was associated with an improved risk-benefit profile compared to temsirolimus,” Dr Rule said.2
Ibrutinib, a Bruton’s tyrosine kinase inhibitor, is already approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with MCL or chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy and patients with CLL and 17p deletion.
- Rule S, Jurczak W, Jerkeman M, et al. Ibrutinib vs temsirolimus: results from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma (MCL). Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
- IMBRUVICA® (ibrutinib) phase 3 RAY data show significant reductions in disease progression versus temsirolimus in relapsed/refractory mantle cell lymphoma patients [news release]. North Chicago, IL: Abbvie; December 7, 2015. http://abbvie.mediaroom.com/2015-12-07-IMBRUVICA-Ibrutinib-Phase-3-RAY-Data-Show-Significant-Reductions-in-Disease-Progression-versus-Temsirolimus-in-Relapsed-Refractory-Mantle-Cell-Lymphoma-Patients. Accessed December 7, 2015.