The current therapeutic scenario for relapsed mantle cell lymphoma

Abstract

Purpose of reviewPatients with relapsing mantle cell lymphoma (MCL) still represent a demanding challenge for the hematooncologist. The dismal prognosis and the absence of generally accepted therapeutic standards hamper the clinical management of such cases. Moreover, the availability of many targeted approaches, in a field so far missing efficient salvage regimens, challenges current therapeutic algorithms in these patients. Recent findingsMolecular targeted drugs provide unprecedented response rates in relapsed and even chemorefractory MCL. Many phase II studies demonstrated impressive antilymphoma activity of compounds such as bortezomib, lenalidomide and temsirolimus, whereas ongoing phase III trials currently assess the 'real world' benefit and the impact on survival, both alone and in combination with chemotherapy or monoclonal antibodies. Recently, the Bruton's tyrosine kinase inhibitor ibrutinib, targeting the B-cell receptor cascade, showed impressive response rates and will be soon available in phase III trials. SummaryIn the present review we focus on the major therapeutic discoveries of the last few years to offer a practical algorithm to select the appropriate treatment in patients with relapsed MCL.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study

“…See Online for appendix randomly permuted blocks and stratifi ed by number of previous lines of therapy (one, two, or three or more) and simplifi ed mantle-cell lymphoma international prognostic index (sMIPI) score 22 (low risk [0-3] vs intermediate risk [4][5] vs high risk [6][7][8][9][10][11]). The randomisation scheme was implemented within the interactive web response system that determined treatment assignment and matching study drug kits.…”

“…Despite recent advances, and with the exception of a small patient population eligible for allogeneic stem cell transplantation, there is no globally recognised standard of care in relapsed mantle-cell lymphoma. [3][4][5] Ibrutinib is a fi rst-in-class, once-daily, oral, covalently binding inhibitor of Bruton's tyrosine kinase. Bruton's tyrosine kinase belongs to the cytoplasmic tyrosine kinase family (Tec kinases) and is important for B-cell receptor signalling and other pathways downstream of the B-cell receptor.…”

Downregulation of deoxycytidine kinase in cytarabine-resistant mantle cell lymphoma cells confers cross-resistance to nucleoside analogs gemcitabine, fludarabine and cladribine, but not to other classes of anti-lymphoma agents

“…Prognosis of relapsed/refractory (RR) MCL is dismal. Currently, there is no second-line standard-of-care for RR-MCL [6]. Available treatment approaches for RR-MCL include cisplatin, fludarabine, cladribine, gemcitabine, temsirolimus, bortezomib, bendamustine, lenalidomide and ibrutinib-based regimen [7-16].…”