A Phase 3 study comparing two therapies in patients with previously treated mantle cell lymphoma has found the drug ibrutinib to be superior to temsirolimus in terms of progression-free survival and overall response rate. The trial’s data are detailed in the abstract titled “Ibrutinib Vs Temsirolimus: Results from a Phase 3, International, Randomized, Open-Label, Multicenter Study in Patients with Previously Treated Mantle Cell Lymphoma (MCL),” presented at the 57th American Society of Hematology (ASH) annual meeting by Dr. Simon Rule, MD, head of lymphoma service at Derrifield Hospital and senior lecturer at Plymouth University Peninsulas School of Medicine and Dentistry.
Ibrutinib (Imbruvica; Janssen, Pharmacyclics) is a first-in-class inhibitor of the enzyme Bruton’s tyrosine kinase, essential for B-cell development. It is FDA-approved for the treatment of chronic lymphocytic leukemia and mantle cell lymphoma (MCL), an aggressive B-cell lymphoma with a poor prognosis. Ibrutinib has previously been shown to be highly effective in MCL patients who fail initial therapy, with overall response rate (ORR) of 65% and complete response (CR) of 20% in Phase 2 studies. However, temsirolimus (Torisel, Pfizer) has demonstrated significantly longer progression-free survival (PFS) when compared to other drugs.
Researchers for this study compared ibrutinib with temsirolimus in 280 patients with relapsed or refractory MCL who had received prior therapy with rituximab. Patients were randomized to receive either oral ibrutinib (139 patients) or intravenous temsirolimus (141 patients). Treatment was carried out until disease progression or unacceptable toxicity. The primary endpoint of the study was PFS and secondary endpoints were ORR, overall survival (OS), time to next treatment (TTNT), time to worsening of lymphoma symptoms, and safety.
The results showed that the median PFS was of 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group. Moreover, at the two-year mark, more patients in the ibrutinib group achieved PFS compared to temsirolimus-treated patients, 41% versus 7%, respectively. Additionally, ORR was significantly higher for ibrutinib when compared to temsirolimus (71.9% vs 40.4%), and the complete response rate was 18.7% for ibrutinib and 1.4% for temsirolimus. Ibrutinib reduced the risk of death by 24% and a greater number of treated patients avoided a worsening of their lymphoma symptoms (27% versus 52% worsening).
Median TTNT with ibrutinib was not reached versus 11.6 months with temsirolimus; median treatment duration was of 14.4 months for ibrutinib and three months for temsirolimus. Discontinuation of treatment due to adverse effects (AEs) was seen in 6.5% of subjects receiving ibrutinib and 25.5% of subjects receiving temsirolimus. The most common AEs for ibrutinib treatment included diarrhea, fatigue, and cough. Most common Grade 3 AEs, including thrombocytopenia (platelet deficiency), anemia, and neutropenia (low concentration of neutrophils), were observed in 67.6% of ibrutinib patients and 87.1% of temsirolimus patients.
Although researchers warn that results might be confounded due to 23% of patients crossing over to the ibrutinib group, the study’s conclusions state that “ibrutinib is superior to temsirolimus for PFS and ORR, and showed preferable tolerability. The results of this phase 3 trial confirm the efficacy and favorable safety profile of ibrutinib shown in phase 2 studies. Future concepts will investigate ibrutinib-based combination approaches for patients with R/R MCL.”