Multiple myeloma gammopathies

Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse

Abstract

Achieving a complete response (CR) is associated with improved overall survival (OS) in multiple myeloma (MM), but data on duration of CR (DurCR) are limited. We evaluated 351 patients (2004–2016), achieving CR with first-line therapy. Patients with sustained DurCR ≥ 24 months (n = 177) had better OS; 150 vs. 81 months, p < 0.001. DurCR ≥ 24 months remained a significant predictor for OS (HR: 0.3, 95% CI: 0.2–0.5, p < 0.001) after adjusting for age, revised ISS stage, transplant and maintenance therapy. Landmark analysis at 24 months demonstrated similar results, OS: 150 vs. 83 months, p < 0.001. Survival benefit persisted even after loss of CR, with median OS being 89 vs. 56 months (p = 0.005), respectively. Patterns of loss of CR were heterogeneous, with biochemical relapse in 59 (25%); symptomatic relapse in 58 (24%); positive immunofixation/monoclonal protein rise not meeting relapse/progression criteria in 88 (37%) and abnormal free light chain ratio in LC MM in 34 (14%) patients. OS from start of first-line therapy was superior in patients starting second-line treatment for biochemical vs. symptomatic relapse (125 vs. 81 months, p = 0.001). This is likely attributable to underlying disease biology and prevention of end-organ damage by early treatment initiation, as benefit was independent of R-ISS stage.

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Author contributions:

SS and SKK designed the study, collected and analyzed data and wrote the manuscript. NT collected the data and contributed to writing and critically appraising the manuscript. AD, MAG, FKB, MQL, DD, ALF, SRH, MAH, WIG, RMW, TK, YLH, PK, RAK, NL, RSG, SVR contributed to writing and critically appraising the manuscript.

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Correspondence to Shaji K. Kumar.

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The authors declare that they have no conflict of interest directly related to this work. Below is a list of all financial disclosures for authors: SS: Honoraria for advisory board, Janssen AD: Research Funding from Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSKPK: Research Funding from Celgene, Takeda MQL: Research Funding from Celgene MAG: Honoraria/consultancy from Ionis, Alnylam, Prothena, Celgene, Janssen, Specytrum, Annexon, Apellis, Amgen, Medscape, Abbvie, Research to Practice, Physcians Education Resource and Teva; SKK: Research Funding and membership on an entity’s Board of Directors or advisory committees: AbbVie, Celgene, Janssen, KITE, Merck. Membership on an entity's Board of Directors or advisory committees: Oncopeptides, Takeda. Research funding from Novartis and Roche.

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