Mantle cell lymphoma: advances in biology and therapy : Current Opinion in Hematology (original) (raw)

Lymphoid biology and diseases: Edited by Nancy Berliner

Lymphoma Service, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

Correspondence to Mitchell R. Smith, MD, PhD, Lymphoma Service, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA Tel: +1 215 728 2674; fax: +1 215 728 3639; e-mail: [email protected]

Abstract

Purpose of review

Mantle cell lymphoma is characterized by dysregulation of cyclin D1, but this is not sufficient for lymphoma development. It is a difficult disease to treat, being incurable with standard chemotherapy and having a median survival of approximately 5 years. The purpose of this review is to update recent advances in mantle cell lymphoma biology with prognostic and potentially therapeutic implications, and mantle cell lymphoma treatment approaches and new agents.

Recent findings

Genetic alterations that cooperate with cyclin D1 have been described that alter proliferation, in particular p27Kip and p16INK4, or apoptosis. Biological factors such as high-proliferation signature defined by gene expression profiles, loss of p27 and presence of mutant p53 confer poor prognosis. Proliferative rate also predicts patient outcome. Clinical criteria such as the international prognostic index, follicular lymphoma international prognostic index or a formula using age, performance status, white blood cell count and lactate dehydrogenase, separate prognostic groups. Not all patients require therapy at diagnosis.

Although the best reported results have been with rituximab–hyperfractionated cyclophosphamide–vincristine–doxorubicin–dexamethasone–methotrexate/cytarabine, a cooperative group study of this regimen appears not quite as successful. Consolidation of remission after rituximab–cyclophosphamide–doxorubicin–vincristine–prednisone with high-dose therapy/stem-cell support prolongs remission and consolidation with radioimmunotherapy shows promise. Intensifying induction by alternating intensified rituximab–cyclophosphamide–doxorubicin–vincristine–prednisone with rituximab and high-dose cytarabine, followed by high-dose therapy appears quite promising. Novel agents active in relapsed disease include bortezomib, mammalian target of rapamycin inhibitors, immunomodulatory agents, antibodies and cyclin pathway-directed agents such as flavopiridol and cyclin-dependent kinase inhibitors.

Summary

New insights into mantle cell lymphoma biology may lead to targeted therapy. Meanwhile, combinations of existing therapeutic approaches seem to have improved outcomes.