Ibrutinib Monotherapy in Patients with Relapsed/Refractory Mantle Cell Lymphoma in Community Clinical Practice Outside of Clinical Trials

Background. Ibrutinib became available for patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in Russia in the end of 2015 based on the results of phase 2 study by M. Wang from MD Anderson Cancer Center (NEJM 2013, Blood 2015). However, pts in routine clinical practice tend to differ significantly from the patients selected for clinical trials, which may lead to poorer results in off study treated patients. Aim. To assess efficacy and toxicity of ibrutinib monotherapy in pts with R/R MCL in routine community clinical practice outside of clinical trials. Materials & Methods. We analyzed the charts of all pts with R/R MCL who started ibrutinib from April 2016 to July 2019 in 7 Moscow's hospitals. The following criteria were used to initiate ibrutinib monotherapy: the age > 18 years, confirmed MCL diagnosis with nuclear hyperexpression of cyclin D1 and/or presence of the t(11;14)(q13;q32); symptomatic relapse or failure to achieve at least PR with a prior regimen. Poor physical status, pancytopenia grade 3-4, infectious complications (except for life-threatening conditions), blastoid variant and the number of previous treatment lines were not regarded as contraindications to ibrutinib therapy. Patients with CNS involvement were excluded from this analysis. Ibrutinib was administered once a day at a dose of 560 mg until progression or intolerable toxicity. Response to therapy was assessed every 2-3 months utilizing CT scan, PET/CT and bone marrow examination were required to confirm CR. Results. 54 pts with R/R MCL received ibrutinib monotherapy between April 2016 and July 2019. 26 pts (48%) were refractory to a prior therapy. The median age was 68 years (range 40-81); 69% of pts were men; ECOG > 2 in 22% of pts. 15 pts (28%) underwent a repeated biopsy before starting ibrutinib. 23 pts (43%) had an aggressive variant of MCL: either blastoid morphology (13/54 at diagnosis and 5/54 after repeated biopsy) or classical morphology with Ki-67>40% (4/54 at diagnosis and 1/54 after repeated biopsy). The median number of previous treatment lines was 2 (1-11). The response was evaluated in 53/54 pts. ORR was 81%, CR rate was 30% in the whole group. Pts with aggressive variants of MCL (group 1) had ORR of 65%, CR rate of 7%. In the group with classical morphology and Ki-67≤40% (group 2) ORR and CR rates were 93% and 47%. 2 pts with a response to therapy stopped ibrutinib early on their own accord, without signs of toxicity above gr.1. The median EF