Phase III trial findings suggest that patients with relapsed or refractory mantle cell lymphoma derive significantly greater benefits from ibrutinib than from temsirolimus therapy.
The results of this direct comparison of the two treatment options approved in the European Union for this patient population “clearly establish ibrutinib as a new standard for treatment” of relapsed or refractory mantle cell lymphoma, says Peter Martin, M.D., of Weill Cornell Medicine, in a comment accompanying the report in The Lancet.
He adds: “Many clinicians expect that, within the next two years, ibrutinib will find its way into the front-line setting for treatment of mantle cell lymphoma in combination with standard chemotherapy”.
In the trial, a total of 280 patients with relapsed or refractory disease who had previously been treated with at least one rituximab-containing regimen were followed up for a median of 20 months.
Median progression-free survival (PFS) was 14.6 months for the 139 patients randomly assigned to receive open-label oral ibrutinib and 6.2 months for the 141 patients given intravenous temsirolimus, a significant difference with a hazard ratio for progression or death of 0.43. The corresponding 2-year PFS rates were 41% and 7%.
Significantly more patients given the Bruton’s tyrosine kinase inhibitor ibrutinib achieved an overall response compared with those given the mammalian target of rapamycin antagonist temsirolimus, with rates of 72% versus 40%. And complete responses were observed in 19% and 1% of patients, respectively.
Although overall survival showed a “tendency towards improvement” with ibrutinib (median not reached vs 21.3 months), the difference was not statistically significant, say the study authors. They point out, however, that 23% of temsirolimus-treated participants crossed over to the ibrutinib arm.
The researchers report that ibrutinib had “better tolerability” than temsirolimus, with fewer patients experiencing treatment-related adverse events of grade 3 or worse (68 vs 87%) and fewer patients discontinuing as a result of unacceptable toxic effects (6 vs 26%).
The improved tolerability was despite ibrutinib treatment duration being four times longer than that for temsirolimus (median 14.4 vs 3.0 months), they observe.
“The results of this phase 3 trial confirm the efficacy and favourable safety profile of ibrutinib as shown in previous phase 2 studies”, conclude Martin Dreyling (Klinikum der Universität München, Germany) and colleagues.
The trial also confirms the positive benefit–risk ratio for ibrutinib as an effective targeted therapy in this setting.
This article first appeared in News Medical.