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[Preprint]. 2023 Oct 23:rs.3.rs-3378634.
doi: 10.21203/rs.3.rs-3378634/v1.

Mode of Progression in Smoldering Multiple Myeloma: A study of 406 patients

S Rajkumar  1 , Nadine Abdallah  2 , Arjun Lakshman  2 , Shaji Kumar  2 , Joselle Cook  1 , Moritz Binder  1 , Prashant Kapoor  1 , Angela Dispenzieri  1 , Morie Gertz  1 , Martha Lacy  1 , Suzanne Hayman  1 , Francis Buadi  1 , David Dingli  1 , Yi Lin  1 , Taxiarchis Kourelis  1 , Rahma Warsame  1 , P Leif Bergsagel  3
Affiliations

Mode of Progression in Smoldering Multiple Myeloma: A study of 406 patients

S Rajkumar et al. Res Sq. .

Update in

  • Mode of progression in smoldering multiple myeloma: a study of 406 patients.
    Abdallah NH, Lakshman A, Kumar SK, Cook J, Binder M, Kapoor P, Dispenzieri A, Gertz MA, Lacy MQ, Hayman SR, Buadi FK, Dingli D, Lin Y, Kourelis T, Warsame R, Bergsagel L, Rajkumar SV. Abdallah NH, et al. Blood Cancer J. 2024 Jan 17;14(1):9. doi: 10.1038/s41408-024-00980-5. Blood Cancer J. 2024. PMID: 38228628 Free PMC article.

Abstract

The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

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Conflict of interest statement

Conflict of Interest Statement: S.V.R reports grants from NIH, outside the submitted work. P.K. received research funding from Takeda Pharmaceuticals, Celgene, and Amgen. A.D. received research funding from Celgene, Millennium Pharmaceuticals, Pfizer, and Janssen and received a travel grant from Pfizer. M.A.G. served as a consultant for Millennium Pharmaceuticals and received honoraria from Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Prothena, Ionis Pharmaceuticals, and Amgen. M.Q.L. received research funding from Celgene. S.K.K. served as a consultant for Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Janssen, and Bristol-Myers Squibb and received research funding from Celgene, Millennium Pharmaceuticals, Novartis, Onyx Pharmaceuticals, AbbVie, Janssen, and Bristol-Myers Squibb. The remaining authors declare no competing financial interests.

Figures

Figure 1
Figure 1. MDEs by SMM risk group.
MDEs in patients with high-risk, intermediate- or low-risk, and unknown risk SMM. Abbreviations: BMPCs: bone marrow plasma cells, FLCs: free light chains, MDE: myeloma-defining event, MRI: Magnetic Reasonance Imaging, SMM: smoldering multiple myeloma.
Figure 2
Figure 2. Presentations at progression by SMM risk group.
Presentations leading to the diagnosis of MM in patients with high-risk, intermediate- or low-risk, and unknown risk SMM. Abbreviations: ED: emergency department, MM: multiple myeloma, SMM: smoldering multiple myeloma.
See this image and copyright information in PMC

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