On February 2018, Professor Simon Rule from Plymouth University Medical School, UK and colleagues, in a letter to the editor of Leukemia, published the final 3-year follow-up results from the RAY phase III clinical trial (NCT01646021). This randomized, open-label study evaluated the efficacy and safety of ibrutinib versus temsirolimus for mantle cell lymphoma patients (MCL), who have previously relapsed from first-line therapy. The results of RAY indicated the superiority of ibrutinib over temsirolimus for MCL, in regards to efficacy, with ibrutinib-mediated progression-free survival (PFS) being significantly higher than that with temsirolimus (14.6 vs 6.2 months, HR 0.43, 95% CI [0.32–0.58]).
- Median follow-up: 38.7 months
- At this time 24% of ibrutinib-treated patients vs 0 temsirolimus-treated patients remained on the initial randomized treatment
- Fifty-five patients (39%) from the temsirolimus group, crossed over to ibrutinib treatment
- Disease progression or relapse was the most common reason for discontinuation for both groups (ibrutinib, 56% vs temsirolimus, 47%)
- Fewer patients discontinued treatment due to adverse events in the ibrutinib arm (9%) rather than the temsirolimus group (28%)
- Median duration of drug exposure:
- Ibrutinib vs temsirolimus: 14.4 vs 0 months
- Median PFS:
- Ibrutinib vs temsirolimus: 15.6 vs 2 months (HR 0.45, 95% CI [0.35–0.60])
- Median PFS for ibrutinib-treated patients was significantly longer independent of the prior treatment lines
- Median overall survival (OS):
- Ibrutinib vs temsirolimus: 30.3 vs 5 months (HR 0.74, 95% CI [0.54–1.02])
- Overall response rate (ORR): missing data
- Ibrutinib vs temsirolimus: 77% vs 47% (Odds ratio 4.27, 95% CI [2.47–7.39])
In this final follow-up analysis of the RAY phase III trial, three years post-treatment, the results were consistent to the ones observed in the primary analysis. In summary, ibrutinib led to significantly longer median PFS, OS and ORR, providing strong evidence on the sustained long-term clinical benefit of ibrunitib for primary relapsed MCL patients.