Clinical efficacy and management of temsirolimus in patients with relapsed or refractory mantle cell lymphoma

摘要

Most patients with mantle cell lymphoma (MCL) relapse within a few years of treatment. Conventional agents provide little benefit, thus identification of new therapies is critical to improve patient outcomes. Temsirolimus, an inhibitor of mammalian target of rapamycin, is an effective, well-tolerated option authorized in Europe for treatment of patients with relapsed/refractory MCL. Intravenous temsirolimus has been extensively studied in MCL and has consistently demonstrated single-agent antitumor activity. In the pivotal phase III trial, treatment with temsirolimus 175 mg weekly for 3 weeks followed by 75 mg weekly (175/75 mg) resulted in significant improvements in progression-free survival (P =.0009) and objective response rate (P =.002) vs. investigator's choice of therapy. Hematologic toxicities (thrombocytopenia, neutropenia) were the principal grade 3/4 adverse events associated with temsirolimus 175/75 mg. Other toxicities included increases in serum cholesterol and triglycerides, hyperglycemia, fatigue, and dyspnea. Overall, the safety profile of temsirolimus is acceptable in this setting, and most toxicities are manageable with dose modification or medical intervention. Clinical studies of temsirolimus in relapsed or refractory MCL patients aim to clarify the optimal treatment schedule and to assess rational combinations with other therapeutic agents, such as rituximab or chemotherapy. Practical considerations are discussed for the clinical use of temsirolimus in patients with MCL.