マントル細胞リンパ腫の診断と治療

Diagnosis and Treatment of Mantle Cell Lymphoma

マントル細胞リンパ腫（mantle cell lymphoma ; MCL）は全非Hodgkinリンパ腫の3～6％を占めるB細胞リンパ腫であり，aggressiveな経過を示すことが多いが，一部に緩徐な経過を示すタイプがあることが知られている．CHOP療法での生存期間中央値は3～5年であるが，リツキシマブ，高用量シタラビン，自家造血幹細胞移植併用の大量化学療法を組み込んだ強力な化学療法の導入によって，65歳以下の若年初発MCLの生存は明らかに改善してきた．自家造血幹細胞移植が非適応である66歳以上の高齢初発MCLでは，R-CHOP療法後のリツキシマブ維持療法が生存改善をもたらすことが検証されている．しかし，適応が限定され，高率の治療関連死亡率を伴う同種移植以外では，MCLに対して治癒をもたらす標準治療は未確立であり，最近の治療戦略でも生存期間中央値は4～6年である．最近，MCLの分子生物学の進歩により，ベンダムスチン，プロテアソーム阻害薬のボルテゾミブ，BTK（Bruton's tyrosine kinase）阻害薬のイブルチニブなど，MCLに対する極めて有望な新薬の開発が進み，MCLのさらなる治療進歩が期待されている．本稿では，MCLの臨床的特徴，診断，標準的治療，新薬の開発動向について述べる．

　MCL（Mantle cell lymphoma）is a recognized lymphoma subtype accounting for 3～6% of all patients with non-Hodgkin lymphoma. The clinical course of MCL ranges from an indolent disease to a rapidly progressive malignancy. It typically has a poor prognosis and a median OS（overall survival）of approximately 3～5 years according to earlier data. Recent improvement has been achieved by the successful introduction of rituximab and dose-intensified approaches, including high-dose cytarabine and autologous stem cell transplantation for patients under 66-years-old. In elderly patients, rituximab maintenance after R-CHOP（rituximab cyclophosphamide, doxorubicin, vincristine, and prednisolone）therapy has been demonstrated to prolong survival. However, with the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are still noncurative, and the corresponding survival curves are characterized by a delayed but continuous decline with a median survival of 4～6 years. In recent years, new insights into the biology of MCL have been obtained, which have provided the rationale for the development of novel therapeutic strategies. Emerging drugs such as bendamustine, the proteasome inhibitors, ibrutinib and others are based on control of the dysregulated cell cycle machinery and impaired apoptotic pathways. The efficacy of these agents as monotherapy has been shown to be comparable with conventional chemotherapy in relapsed MCL, and combination strategies are currently being investigated in clinical trials.