CNS prophylaxis for diffuse large B-cell lymphoma

Author(s): Toby A Eyre, MD1;Prof Kerry J Savage, MD2;Prof Chan Y Cheah, MD3,4,5;Prof Tarec C El-Galaly, MD6,7,8;Katharine L Lewis, MD3,4,5;Pamela McKay, MD9;Matthew R Wilson, MD10;Prof Andrew M Evens, PhD11,12;Sabela Bobillo, MD13;Diego Villa, MD14;Matthew J Maurer, DMSc15;Kate Cwynarski, PhD16;Prof Andrés J M Ferreri, MD17
Source: DOI:doi.org/10.1016/S1470-2045(22)00371-0
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

This is a nice historical accounting of this sometimes-challenging paradigm. No randomized, prospective trials exist to guide practice management.  The question in clinic is often, when to use prophylaxis and when not? The CNS-IPI is the best scoring system validated in the Rituximab era.  This did not account for double/triple hit genetics, ABC subtypes or sites of disease (gonads, >3 sites).  A high score or any of these groups are generally those that benefit the most from CNS-prophylaxis. The field has moved away from IT-MTX therapy to HD-IV-MTX since most secondary CNSL is parenchymal in nature. Most relapses occur at months 6-9 so sooner is probably better in terms of timing.

SUMMARY

CNS relapse in the brain parenchyma, eyes, or leptomeninges is an uncommon but devastating complication of diffuse large B-cell lymphoma. CNS prophylaxis strategies, typically involving intrathecal or high-dose antimetabolites, have been developed in the front-line treatment setting with the aim to reduce this subsequent risk. Clinical and biological features associated with elevated risk are increasingly well defined and are discussed in this Review. This Review summarises both the historical and current developments in this challenging field, provides a nuanced discussion regarding current reasons for and against standard prophylactic measures, outlines evidence for the timing of prophylactic measures when delivered, and reflects on possible future developments.

Author Affiliations

Toby A Eyre, MD1;Prof Kerry J Savage, MD2;Prof Chan Y Cheah, MD3,4,5;Prof Tarec C El-Galaly, MD6,7,8;Katharine L Lewis, MD3,4,5;Pamela McKay, MD9;Matthew R Wilson, MD10;Prof Andrew M Evens, PhD11,12;Sabela Bobillo, MD13;Diego Villa, MD14;Matthew J Maurer, DMSc15;Kate Cwynarski, PhD16;Prof Andrés J M Ferreri, MD17 1Department of Haematology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom;2British Columbia Cancer Centre for Lymphoid Cancer and the University of British Columbia, BC Cancer, Vancouver, BC, Canada;3Department of Haematology, Sir Charles Gairdner Hospital, Perth, WA, Australia;4Department of haematology, University of Western Australia, Perth, WA, Australia;5Linear Clinical Research, Perth, WA, Australia;6Department of Hematology, Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark;7Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;8Department of Hematology, Odense University Hospital, Odense, Denmark;9Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom;10Department of Haematology, Queen Elizabeth University Hospital, Glasgow, United Kingdom;11Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA;12Departments of Medicine and Maternal Fetal Medicine, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA;13Department of Hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Barcelona, Spain;14British Columbia Cancer Centre for Lymphoid Cancer and the University of British Columbia, BC Cancer, Vancouver, BC, Canada\;15Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA;16Department of Haematology, University College London Hospitals, London, United Kingdom;17Lymphoma Unit, Department of Onco-Haematology, IRCCS San Raffaele Scientific Institute, Milan, Italy

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