Despite unprecedented clinical activity in mantle cell lymphoma (MCL), primary and acquired resistance to ibrutinib is common. The outcomes and ideal management of patients who experience ibrutinib ...failure are unclear. We performed a retrospective cohort study of all patients with MCL who experienced disease progression while receiving ibrutinib across 15 international sites. Medical records were evaluated for clinical characteristics, pathological and radiological data, and therapies used pre- and postibrutinib. A total of 114 subjects met eligibility criteria. The median number of prior therapies was 3 (range, 0-10). The Mantle Cell Lymphoma International Prognostic Index (MIPI) scores at the start of ibrutinib were low, intermediate, and high in 46%, 31%, and 23% of patients, respectively. Of patients with available data prior to ibrutinib and postibrutinib, 34 of 47 and 11 of 12 had a Ki67 >30%. The median time on ibrutinib was 4.7 months (range 0.7-43.6). The median overall survival (OS) following cessation of ibrutinib was 2.9 months (95% confidence interval CI, 1.6-4.9). Of the 104 patients with data available, 73 underwent subsequent treatment an average of 0.3 months after stopping ibrutinib with a median OS of 5.8 months (95% CI, 3.7-10.4). Multivariate Cox regression analysis of MIPI before postibrutinib treatment, and subsequent treatment with bendamustine, cytarabine, or lenalidomide failed to reveal any association with OS. Poor clinical outcomes were noted in the majority of patients with primary or secondary ibrutinib resistance. We could not identify treatments that clearly improved outcomes. Future trials should focus on understanding the mechanisms of ibrutinib resistance and on treatment after ibrutinib.
•Patients with mantle cell lymphoma who progressed during treatment with ibrutinib have a poor outcome.•There are no therapies that appear to be uniquely successful in the postibrutinib setting. The postibrutinib setting is an unmet need.
BACKGROUND Chronic lymphocytic leukemia (CLL) is the most common leukemia affecting older adults. As such, many of these patients suffer from co-existing disease states, and the provider must take ...these comorbidities into account when determining a treatment regimen. The widespread use of monoclonal antibodies (mAbs) has drastically changed the treatment landscape of multiple diseases, ranging from leukemia to autoimmune conditions such as rheumatoid arthritis. CASE REPORT We present the case of a patient who had progression of his CLL and rheumatoid symptoms on rituximab therapy, and was subsequently treated with the second-generation anti-CD20 antibody obinutuzumab. Obinutuzumab therapy was associated with simultaneous sustained remission of both disease states, allowing for discontinuation of all other disease-modifying anti-rheumatic drugs (DMARDs), and prolonged remission of his CLL. CONCLUSIONS While anti-CD20 antibodies have a clear role in the treatment of leukemia and inflammatory conditions, the success of obinutuzumab in RA has not been fully evaluated. We present this case as further evidence of the strong role of anti-CD 20 therapy in multiple conditions, and the unique opportunity for control of simultaneous disease states through targeted inhibition of shared common pathways.
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