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Current approaches and advance in mantle cell lymphoma treatment.

ABSTRACT: Mantle cell lymphoma (MCL) is a set of heterogeneous non-Hodgkin lymphoma characterized by involvement of lymph nodes, spleen, bone marrow and blood. Under conventional treatment, survival time is 4 to 5 years with short remission period and there is still no standard treatment for MCL. In general, a close observation period called "watchful waiting" is used in elderly patients with low-risk slow clinical progress. And intensive chemotherapy including high-dose of cytarabine ± autologous hematopoietic stem cell transplantation (auto-HSCT) is recommended for younger and fit patients. Allogenic stem cell transplantation (allo-SCT) and drugs targeting the cell metabolic pathway, such as bortezomib (NF-?B inhibitor) and lenalidomide (anti-angiogenesis drug), are considerable treatments for relapsed/refractory patients. Clinical trials and less intensive chemotherapy such as R-CHOP (rituximab with cyclophosphamide, hydroxydaunomycin, oncovin and prednisone) and R-bendamustine should be considered for elderly MCL patients who are at intermediate/high risk. Recent clinical trials with ibrutinib (Bruton's Tyrosine Kinase inhibitor) and temsirolimus (mTOR inhibitor) have shown excellent efficacies in the treatment of MCL. This review will introduce the present status and major therapeutic progress in the treatment of MCL over recent years in order to provide a cutting edge to look into promising clinical progress of MCL.

SUBMITTER: Liu Y

PROVIDER: S-EPMC4923656 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Current approaches and advance in mantle cell lymphoma treatment.

Liu Yao Y Zhang Xi X Zhong Jiang-Fan JF

Stem cell investigation 20150929

Mantle cell lymphoma (MCL) is a set of heterogeneous non-Hodgkin lymphoma characterized by involvement of lymph nodes, spleen, bone marrow and blood. Under conventional treatment, survival time is 4 to 5 years with short remission period and there is still no standard treatment for MCL. In general, a close observation period called "watchful waiting" is used in elderly patients with low-risk slow clinical progress. And intensive chemotherapy including high-dose of cytarabine ± autologous hematop ...[more]

PMID: 27358886

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Project description:Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy. In general, given the unfavorable risk-benefit profile, older MCL patients should be spared intensive strategies, while younger and fit patients can be considered for intensive strategies. The bendamustine and rituximab (BR) regimen is becoming an increasingly popular treatment option among the elderly population, with improved progression-free survival (PFS) and acceptable side-effect profile. Although rituximab maintenance after R-CHOP improves survival outcomes in elderly patients, no clinical trial to date has shown statistical significance to support the use of rituximab maintenance after BR induction in older patients. In young and fit patients with MCL, an intensive strategy to maximize the length of first remission has emerged as a worldwide standard of care. With current high-dose cytarabine-containing immunochemotherapy regimens followed by autologous stem cell transplantation, the median PFS has exceeded 7 years. In the relapsed or refractory (R/R) setting, reduced intensity conditioning allogeneic hematopoietic stem cell transplantation may offer the highest likelihood of long-term survival in young R/R MCL patients, at the cost of increased risk of non-relapse mortality and chronic graft versus host disease. Novel agents targeting activated pathways in MCL cells, such as bortezomib, lenalidamide, ibrutinib and temsirolimus are now available for the management of R/R disease.

Project description:BackgroundMantle-cell lymphoma is generally incurable. Initial treatment is not standardized but usually includes cytotoxic chemotherapy. Lenalidomide, an immunomodulatory compound, and rituximab, an anti-CD20 antibody, are active in patients with recurrent mantle-cell lymphoma. We evaluated lenalidomide plus rituximab as a first-line therapy.MethodsWe conducted a single-group, multicenter, phase 2 study with induction and maintenance phases. During the induction phase, lenalidomide was administered at a dose of 20 mg daily on days 1 through 21 of every 28-day cycle for 12 cycles; the dose was escalated to 25 mg daily after the first cycle if no dose-limiting adverse events occurred during the first cycle and was reduced to 15 mg daily during the maintenance phase. Rituximab was administered once weekly for the first 4 weeks and then once every other cycle until disease progression. The primary end point was the overall response rate. Secondary end points included outcomes related to safety, survival, and quality of life.ResultsA total of 38 participants were enrolled at four centers from July 2011 through April 2014. The median age was 65 years. On the basis of the Mantle Cell Lymphoma International Prognostic Index scores, the proportions of participants with low-risk, intermediate-risk, and high-risk disease at baseline were similar (34%, 34%, and 32%, respectively). The most common grade 3 or 4 adverse events were neutropenia (in 50% of the patients), rash (in 29%), thrombocytopenia (in 13%), an inflammatory syndrome ("tumor flare") (in 11%), anemia (in 11%), serum sickness (in 8%), and fatigue (in 8%). At the median follow-up of 30 months (through February 2015), the overall response rate among the participants who could be evaluated was 92% (95% confidence interval [CI], 78 to 98), and the complete response rate was 64% (95% CI, 46 to 79); median progression-free survival had not been reached. The 2-year progression-free survival was estimated to be 85% (95% CI, 67 to 94), and the 2-year overall survival 97% (95% CI, 79 to 99). A response to treatment was associated with improvement in quality of life.ConclusionsCombination biologic therapy consisting of lenalidomide plus rituximab was active as initial therapy for mantle-cell lymphoma. (Funded by Celgene and Weill Cornell Medical College; ClinicalTrials.gov number, NCT01472562.).

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Current approaches and advance in mantle cell lymphoma treatment.

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Current approaches and advance in mantle cell lymphoma treatment.

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