Ibrutinib effective at first MCL relapse in a real-world study

A real-world analysis builds on trial evidence that ibrutinib is most effective for patients with mantle cell lymphoma (MCL) at first relapse.

The Bruton tyrosine kinase inhibitor is now widely available in the relapsed/refractory MCL setting, but there remains no consensus on the optimal timing of the agent. A pooled trial analysis previously showed a substantially better progression-free survival when ibrutinib was used at first relapse compared to its use at a later relapse.

“However, general applicability of trial findings to real‐world populations enriched with frailer patients prone to drug toxicity is unknown, and uncertainties persist regarding post‐ibrutinib outcomes,” wrote study authors led by Dr Rory McCulloch, of University Hospitals Plymouth NHS Trust, in the British Journal of Haematology.

The authors conducted a retrospective real-world analysis of 211 patients with relapsed/refractory MCL, all of whom received ibrutinib as second-line therapy at multiple centres across the NHS. The median age in the cohort was 73 years.

The overall response rate to ibrutinib was 69%, with a complete response rate of 27%. The median PFS was 17.8 months, and the median OS was 23.9 months. In 40% of evaluable patients, the PFS with ibrutinib exceeded the PFS achieved with frontline therapy.

Drug-related adverse events resulted in a dose reduction of ibrutinib in 10% of patients, and discontinuation of therapy in 5%.

Of the 152 patients who stopped ibrutinib, most did so for progressive disease, and 43% received further systemic therapy. There was a trend toward improved survival with post-ibrutinib rituximab, bendamustine, and cytarabine, compared with other systemic treatments, with a median OS of 14.0 months vs. 3.6 months (p = .06).

The authors noted that the response rates in this real-world study mirrored those in the previously published pooled trial analysis, in spite of this being an unselected group. The PFS is slightly reduced from that analysis (17.8 months vs. 25.4 months), but still exceeds that observed in patients receiving ibrutinib at later relapses on clinical trials.

The median OS showed a “marked divergence” from the previous analysis (23.9 months vs. 61.6 months), which likely is due to large differences in patient demographics. Most notably, the median age in the real-world study was 73 years, compared with 67 years in the trials, and 24% of the real-world cohort had an ECOG performance status of 2 or higher, compared with 6% in the trial analysis.

“Our findings consolidate the central role of ibrutinib in MCL therapy and support use at first relapse,” the authors wrote. “Developing ibrutinib combination therapies for high risk patients and more effective salvage therapies remains a priority.”

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