Potential for chemotherapy-free standard of care in advanced mantle cell lymphoma

By Shreeya Nanda, Senior medwireNews Reporter

The combination of ibrutinib and rituximab shows activity in patients with relapsed or refractory mantle cell lymphoma, suggests research published in The Lancet Oncology.

“Our findings could lead to the use of ibrutinib and rituximab as a frontline combination, with a possibility of chemotherapy-free treatment”, says the team from The University of Texas MD Anderson Cancer Center, in Houston, USA, adding, however, that definitive conclusions cannot be drawn until phase III trial results become available.

In this phase II trial, concurrent open-label ibrutinib and rituximab elicited an objective response in 88% of 50 patients with stage IV disease who had previously received a median of three treatments. Of the responses observed, 44% were complete responses while 44% were partial.

Although median progression-free and overall survival had not been reached at the time of analysis, the corresponding 1-year rates were 75.0% and 85.5%.

When study participants were stratified by expression levels of the proliferation marker Ki-67, all 37 patients with levels below 50% achieved an objective response, with 54% achieving a complete response. By contrast, an objective response was observed in only half of the 12 patients with levels of at least 50%, of which just two had complete responses.

And seven of the nine patients who discontinued treatment as a result of disease progression had Ki-67 levels of 50% or higher.

Therefore, Michael Wang and co-researchers suggest that Ki-67 could serve as a predictive marker of response to ibrutinib plus rituximab in this patient population.

Atrial fibrillation was the most frequent grade 3 side effect, observed in 12% of the study cohort. But the authors find this “unsurprising” given that the study population was elderly and had been exposed to agents with associated cardiac toxicity, such as doxorubicin.

Adverse events of grade 4 occurred in two patients, one case each of diarrhoea and neutropenia. Five patients discontinued therapy as a result of adverse events and one of the two deaths that occurred during the course of the study was considered related to treatment.

But as the majority of side effects were of grade 1 or 2, Wang et al conclude that the combination is well tolerated, and therefore “could become a useful combination regimen in daily practice”.

Simon Rule (Plymouth University Peninsula Schools of Medicine and Dentistry, UK) notes in a linked comment that the addition of rituximab to the Bruton’s tyrosine kinase inhibitor “clearly improves efficacy”.

But he wonders whether some of the reported improvement could be attributed to the smaller proportion of patients with high-risk Mantle Cell International Prognostic Index scores in this trial than in the previously reported trial of ibrutinib alone (12 vs 49%).

The commentator adds that “longer term follow-up is needed to see if the increase in responses recorded will translate into an improvement in response duration.”

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