Walking a tightrope: clinical use of ibrutinib in mantle cell lymphoma in the elderly

Abstract

Representative clinical case. A 74-year-old male patient was diagnosed with stage 3 mantle cell lymphoma in 2012. Because he was ineligible for intensive treatment (age, previous myocardial infarction [MI]), he received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy for 6 cycles (reaching complete response) and then rituximab maintenance (RM) for 2 years. One year after the end of RM, he relapsed with disseminated disease. He was started on ibrutinib 560 mg/day. Two weeks after the start of ibrutinib, he developed grade 3 diarrhea that required interruption of ibrutinib. Two weeks after the regular dose was restarted (month 3), the patient had repeated bleeding (patient was receiving aspirin for previous MI) and had to stop ibrutinib again. Because the patient was in partial response (PR) with lack of disease-associated symptoms, he was restarted on ibrutinib 280 mg/day with no further adverse events, and he had maintained PR at last follow-up (month 9 on ibrutinib). Learning Objectives• Treatment of MCL varies significantly between elderly and young patients • In elderly MCL, the achievement of deep responses should balance the management of co-morbidities and treatment toxicity • New targeted agents, like ibrutinib, could potentially change the treatment paradigm for elderly MCL thanks to their high efficacy associated with manageable toxicity Mantle cell lymphoma (MCL) represents 6% to 8% of non-Hodgkin lymphomas and has an annual incidence of 1 to 2 per 100 000 people in the United States and the European Union. 1 MCL typically presents predominantly in males who have late-stage disease and a median age at diagnosis of 65 to 68 years.2,3 More recent real-world studies indicate that the median age of patients with MCL may be older than 70 years.4-6 Therefore, MCL is considered a disease of the elderly, and a significant subset of patients displays reduced performance status at diagnosis. Overall, MCL has a poor prognosis with 4 to 5 years of median survival, 7 and elderly patients (age 65 to 70 years or older) have a worse outcome compared with younger patients, mostly because of increased treatment-related toxicity. This is reflected by the fact that age is one of the 4 key prognostic factors of the Mantle Cell Lymphoma International Prognostic Index. Elderly MCL patients are typically excluded from dose-intensified chemotherapeutic approaches and stem cell transplantation. However, in the absence of contraindications, they usually receive rituximab plus a chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]; bendamustine; or other drugs), with possible rituximab maintenance for 2 years after CHOP (the role of rituximab maintenance after bendamustine is still controversial 9 ). 1,10 Unfortunately, the majority of elderly MCL patients will relapse and then have a very poor prognosis. Managing relapsing or refractory (r/r) MCL is particularly challenging because these individuals often have a reduced performance status an...

Targeted Drugs as Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma

“…Ibrutinib is associated with toxicities including cytopenias, gastrointestinal symptoms, edema, and musculoskeletal symptoms, but these are typically mild [ 55 ]. Risk of bleeding seems to be increased with ibrutinib due to off-target effects on platelet function, and concurrent use of vitamin K antagonist anticoagulation is generally advised against [ 56 ].…”