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Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that has an aggressive clinical course and poor prognosis. Although current front-line combination chemo-immunotherapies followed by autologous stem-cell transplantation (ASCT) have improved the outcomes of affected patients (pts), this disease is still incurable and relapse is common. Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase that showed significant activity in relapsed/refractory MCL in clinical trials, but in real-life routine, the efficacy and safety may not always mirror those seen in clinical trials.

We investigated the clinical use of ibrutinib as a single-agent in 31 pts with relapsed or refractory MCL to obtain additional information about predictive factors, outcomes and toxicity in a real-life context.

We studied a group of 31 pts treated (or still in treatment) with ibrutinib to assess effectiveness in terms of overall response rate, complete response rate, progression free survival and adverse events (AEs) in a real-life context. Data were collected also with reference to clinical and biological characteristics of the disease (MIPI, MIPIb, bone marrow involvement, stage, histology, presence of bulky mass and/or extranodal disease) both at the time of diagnosis and at the time of the start of ibrutinib therapy, and to the type and number of previous therapies.

At the start of ibrutinib therapy, the median age was 70 years (range, 45-82), 100% of pts had high risk MCL according to the MIPI score, 83.9% of pts had disease stage III or higher, 41.9% of pts had bone marrow involvement, and 45.2% of pts presented extranodal involvement of MCL. 26 pts were treated for relapsed MCL, 5 for refractory disease. They had received a median of 2 (range, 1-5) prior regimens including different chemo-immunotherapy schemes, ASCT and newer agents such us bortezomib, lenalidomide, temsirolimus. We observed 6 complete responses, 1 after only 2 months of therapy, the others within 6 months of therapy. After 15 months, we observed 4 relapses, characterized by leukemic disease and one of them also presented central nervous system involvement, and 8 progression. 80% of pts treated for refractory disease presented progression within 6 months. The most common AEs were fatigue (13% of pts) and weight increase (13% of pts), followed by diarrhea and bleeding (grade ≤ 2) (6.4% of pts). The most common hematologic event observed was neutropenia (9.7% of pts, grade ≤ 2). With an estimated median follow-up of 6 months (range, 4-29), 19 pts are still receiving treatment, 12 have discontinued therapy for relapse or progression of disease. Follow-up is still ongoing.

Single-agent oral ibrutinib shows a high response rate and produces rapid responses regardless of the number and quality of prior regimens. However, the quality and time of response does not seem to be predictive of a better PFS or longer duration of response. Furthermore, resistance to ibrutinib in pts with MCL is associated with fulminant, severe progression. Ibrutinib is well tolerated also in real-life experience. The weight increase in 13% of pts suggests that ibrutinib may have an anabolic effect, including alterations in blood pressure and lipid profile. Larger cohorts of pts and longer follow-up are warranted to confirm these preliminary data.