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Lookup NU author(s): Professor Graham Jackson
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© 2023 The American Society of HematologyPrediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in patients in the National Cancer Research Institute Myeloma XI (MyXI) trial. Patients in the MyXI trial randomized to Len maintenance or observation after ASCT were genetically profiled for t(4;14), t(14;16), t(14;20), del(1p), gain(1q), and del(17p) and co-occurrence of risk markers was computed. Progression-free survival (PFS), subsequent progression (PFS2), and overall survival (OS) were calculated from maintenance randomization, and groups were compared using Cox proportional hazards regression. Of 556 patients, 17% with double-hit multiple myeloma (MM) (≥2 risk markers), 32% with single-hit (1 risk marker), and 51% without risk markers were analyzed. Single-hit MM derived the highest PFS benefit from Len maintenance, specifically, isolated del(1p), del(17p), and t(4;14), with ∼40-fold, 10-fold, and sevenfold reduced risk of progression or death (PFS), respectively, compared with observation. This benefit translated into improved PFS2 and OS for this group of patients compared with observation; median PFS was 10.9 vs 57.3 months for observation vs Len maintenance. Patients with isolated gain(1q) derived no benefit, and double-hit MM limited benefit (regardless or risk lesions involved) from Len maintenance. Extended genetic profiling identifies patients deriving exceptional benefit from Len maintenance and should be considered for newly diagnosed patients to support management discussions along their treatment pathway. This trial was registered at www.isrctn.com/ISRCTN49407852 as # ISRCTN49407852.
Author(s): Panopoulou A, Cairns DA, Holroyd A, Nichols I, Cray N, Pawlyn C, Cook G, Drayson M, Boyd K, Davies FE, Jenner M, Morgan GJ, Owen R, Houlston R, Jackson G, Kaiser MF
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2023
Volume: 141
Issue: 14
Pages: 1666-1674
Print publication date: 06/04/2023
Online publication date: 23/12/2022
Acceptance date: 04/12/2022
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: Elsevier B.V.
URL: https://doi.org/10.1182/blood.2022018339
DOI: 10.1182/blood.2022018339
PubMed id: 36564045
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