Both ibrutinib and temsirolimus are effective in patients with previously treated mantle cell lymphoma (MCL). A recent randomized, head-to-head, phase III study showed that ibrutinib led to longer progression-free survival (PFS) and a higher objective response rate (ORR) in these patients.
“MCL patients typically achieve only short-term remissions with conventional therapies, so the positive results seen with ibrutinib in this phase III trial are particularly striking,” said Simon Rule, MD, from the Department of Hematology at Derriford Hospital in Plymouth, United Kingdom, said during his presentation at the 2015 ASH Annual Meeting in Orlando, Florida, last month.
In the open-label RAY study, a total of 280 patients (median age = 68 years; range = 34-88 years) were randomized 1:1 to receive:
- Ibrutinib: 560 mg once-daily (n=139)
- Temsirolimus: 175 mg, administered intravenously on days 1, 8, and 15 of cycle one followed by 75 mg on days 1, 8, and 15 during all subsequent cycles (n=141)
All patients had received one or more prior therapies containing rituximab, and all had experienced disease progression after receiving a median of two prior lines of therapy (range = 1-9). Nearly two-thirds of the patients in the study had intermediate- or high-risk disease.
PFS was the study’s primary endpoint; secondary endpoints included ORR, overall survival (OS), time to next treatment, time to worsening of lymphoma symptoms, and adverse events (AEs).
At the time of this reporting, the median follow-up was 20 months. Patients treated with ibrutinib had a statistically significant reduction in the risk of progression or death compared with temsirolimus (median PFS=14.6 months vs. 6.2 months, respectively; hazard ratio [HR] = 0.43; 95% CI 0.32-0.58; p<0.0001). After two years of follow-up, the PFS rate was 41 percent for ibrutinib and 7 percent for temsirolimus.
The ORR was also significantly higher for those receiving ibrutinib compared to temsirolimus: 71.9 percent versus 40.4 percent (p<0.0001). Median OS had not yet been reached in the ibrutinib cohort, but was 21.3 months in the temsirolimus cohort (HR=0.76; 95% CI 0.53-1.09).
Twenty-six patients (18.7%) in the ibrutinib group and two patients (1.4%) in the temsirolimus group achieved a complete response (CR).
The median treatment duration was 14.4 months for ibrutinib and three months for temsirolimus. Median time-to-next-treatment was 11.6 months for those taking temsirolimus, but had not been reached in the ibrutinib arm.
Dr. Rule noted that 32 patients (23%) initially enrolled in the temsirolimus arm crossed over to receive ibrutinib treatment. For patients who received other anti-cancer therapies after disease progression with either ibrutinib or temsirolimus, ORR was about 20 percent in each group; however, the rate of complete response was higher among those who received therapy after ibrutinib than after temsirolimus.
The most common treatment-related AEs for ibrutinib were diarrhea, fatigue, and cough, while the most common AEs associated with temsirolimus were thrombocytopenia, anemia, and diarrhea. The incidence of treatment-related AEs was consistently lower for patients treated with ibrutinib compared with temsirolimus, and fewer patients discontinued treatment due to AEs (12.9% vs. 29.5%). Disease progression was the most common cause of death in the ibrutinib arm, while AEs were the most common causes of death in the temsirolimus arm.
“This study provides further evidence that ibrutinib should be considered the treatment of choice for patients with previously treated MCL,” Dr. Rule said. Future planned trials will investigate the safety and efficacy of ibrutinib in combination with other treatments, as well as earlier in the disease course.
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). Abstract #469. Presented at the ASH Annual Meeting, December 7, 2015; Orlando, Florida.