Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma—a “real world” study

Abstract

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses.

Impact of novel therapies for mantle cell lymphoma in the real world setting: a report from the UK's Haematological Malignancy Research Network (HMRN)

“…Whilst guidelines are available in the UK for first line therapy, there is no agreed standard of care for the management of patients with relapsed/refractory (RR) MCL (McKay et al , ; Zaja et al , ; Atilla et al , ; Dreyling et al , ; Martin et al , ; National Comprehensive Cancer Network, ); options including additional immunochemotherapy, or treatment with novel targeted agents, such as ibrutinib (Dreyling et al , ; Wang et al , ; Martin et al , ). In this context, while real‐world data has linked recent changes in first‐line management to improvements in survival for the Nordic countries and parts of France (Abrahamsson et al , , ; Leux et al , ), as well as for RR MCL in Belgium(Epperla et al , ), comparable data from other countries are exceedingly sparse. Such data are, however, required in order to monitor the impact of therapeutic change at the population level, and to inform decision‐making for clinicians and regulatory agencies.…”

Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects

“…Epperla et al () reported an ORR of 65%, a median duration of response of 17 months, and a median OS of 22 months. Post‐ibrutinib therapy included a variety of regimens in this cohort (Table ).…”

“…Multivariate analysis of OS, taking into account the MCL International Prognostic Index (MIPI) and the type of subsequent therapy, did not show statistically significant predictive factors, from the start of the post-ibrutinib therapy (Martin et al, 2016). Epperla et al (2017) reported an ORR of 65%, a median duration of response of 17 months, and a median OS of 22 months. Post-ibrutinib therapy included a variety of regimens in this cohort (Table II).…”

“…Post‐ibrutinib therapy included a variety of regimens in this cohort (Table ). The median OS after ibrutinib failure was only 2·5 months (Epperla et al , ).…”

“…Post-ibrutinib therapy included a variety of regimens in this cohort (Table II). The median OS after ibrutinib failure was only 2Á5 months (Epperla et al, 2017). Dreyling et al (2016) reported a phase 3 randomized trial in 280 patients with R/R MCL comparing single agent ibrutinib to temsirolimus.…”