Treatment approaches for patients with TP53-mutated mantle cell lymphoma. Issue 2 (February 2023)

• Record Type: Journal Article
• Authors: Lew, Thomas E; Minson, Adrian; Dickinson, Michael; Handunnetti, Sasanka M; Blombery, Piers; Khot, Amit; Anderson, Mary Ann; Ritchie, David; Tam, Constantine S; Seymour, John F
• Is Part Of: Lancet. Volume 10:Issue 2(2023)
• Page Start: e142
• Page End: e154
• Publication Date: 2023-02
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15005
• DOI: 10.1016/S2352-3026(22)00355-6
• Languages: English
• ISSNs: 2352-3026

Abstract

Summary: Mantle cell lymphoma is an uncommon subtype of lymphoma characterised by clinical and biological heterogeneity. Although most patients with mantle cell lymphoma have durable responses after chemoimmunotherapy, there is a need to prospectively identify high-risk subsets of patients for whom disease control with standard chemotherapy will be short lived. Among the available prognostic factors, TP53 mutations are uniquely informative owing to their strong association with early disease progression and death among patients receiving conventional chemoimmunotherapy, with the highest negative prognostic value compared with other established risk indicators, including the mantle cell lymphoma international prognostic index, histological features, elevated Ki-67, and other genetic lesions. The poor outcomes for patients with TP53 -mutated mantle cell lymphoma receiving chemoimmunotherapy and second-line Bruton tyrosine kinase inhibitors represent an urgent need for alternative approaches. In this Review, we synthesise the available data to inform the management of this high-risk subset of patients and present a treatment strategy prioritising clinical trials and early use of cellular therapies.