Journal
LEUKEMIA & LYMPHOMA
Volume 59, Issue 12, Pages 2769-2781Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2018.1457148
Keywords
Mantle cell lymphoma; ibrutinib; venetoclax; resistance mechanisms
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Funding
- Leukemia Lymphoma Society [0862-15]
- National Health and Medical Research Council of Australia
- NHMRC Postgraduate fellowship
- HSANZ Young Investigator Fellowship
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Novel targeted therapeutics has significantly improved the outlook of patients with relapsed/refractory mantle cell lymphoma (R/R MCL). Despite significant efficacy, one of the major limitations of these targeted agents is presence of primary or acquired resistance to these novel drugs. Patients who fail primary therapy especially with ibrutinib have poor outcomes and may respond poorly to subsequent therapies. Hence, it is important to understand resistance mechanisms a priori to identify patients who are unlikely to respond, and to explore alternative therapeutic strategies. In this review, we will discuss the currently most active two drugs: ibrutinib and venetoclax, both of which have shown high response rates in R/R MCL. We review current understanding of genomic alterations associated with resistance, and discuss possible strategies to overcome these resistance mechanisms.
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