Exploiting gene mutations and biomarkers to guide treatment recommendations in mantle cell lymphoma

ABSTRACT

Introduction: While there has been an improvement in the treatment of mantle cell lymphoma (MCL) in both median progression-free survival (PFS; >7–8 years) and overall survival (OS; >10–12 years), patients with high-risk features such as high risk MIPI (mantle cell international prognostic index), high Ki-67 (≥30%), or blastoid variants still carry poor outcome with a median OS of 3 years. Furthermore, patients with high-risk molecular features, such as TP53 mutations, show dismal outcome, with a median OS of 1.8 years, regardless of therapy used. Further studies have led to the development of six novel drugs approved for the treatment of relapse/refractory (R/R) MCL, leading to improved survival even in refractory or high-risk patients.

Areas covered: This review covers clinical biological and molecular features that impact MCL outcome with current standards. Beyond the recognition of separate subentities, we review how high-risk molecular features have paved the way toward a new paradigm away from chemoimmunotherapy.

Expert opinion: Progress in novel therapies and in routine diagnostics, particularly next-generation sequencing (NGS), support the development of new treatment strategies, not based on the dose intensity/age dichotomy, which may prevent the need for chemotherapy and improve outcome across MCL including in high-risk subsets.

KEYWORDS:

• Mantle cell
• novel therapies
• molecular high-risk features
• p53
• complex karyotypes
• ngs
• mrd
• precision medicine

Declaration of interest

A Goy reports research funding to institution from Acerta; personal fees, consulting, and research funding to institution from Celgene; research funding to institution from Constellation; and research funding to institution from Infinity; research funding to institution from Infinity Verastem; personal fees, consulting, and research funding to institution from Janssen; research funding to institution from Karyopharm; personal fees, consulting, and research funding to institution from Pharmacyclics/Abbvie; personal fees, consultant, and advisory board from Elsevier’s PracticeUpdate Oncology; personal fees and advisory board from Gilead; personal fees and consulting from Michael J Hennessey Associates, INC; personal fees and moderator from OncLive Peer Exchange; personal fees, faculty member and chair and consulting faculty from Physcians Education Resource, LLC; personal fees and consulting from Xcenda; consulting, and research funding to institution from Genentech-Hoffman La Roche; personal fees, advisor, steering committee, research funding to institution from Astrazenca; research funding to institution from Genentech; research funding to institution from Hoffman La Roche; personal fees and steering committee and research funding to institution from MorphoSys and Incyte; personal fees, board of directors, and stock from COTA; personal fees, board of directors, and stock options from Genomic Testing Cooperative; personal fees, advisory role, advisory board, and research funding to institution, from Kite Pharma; personal fees and consulting from Novartis; personal fees and consulting faculty from Rosewell Park; personal fees, and scientific advisory board from Vincerx; personal fees, board of directors, and stock options from Resilience; personal fees, and consulting from Medscape; personal fees, and consulting from BMS outside the submitted work. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.