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Multiple myeloma: 2022 update on diagnosis, risk stratification, and management

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Rajkumar, S. Vincent·2022·American Journal of Hematology
DOI 10.1002/ajh.26590PMC PMC9387011
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Abstract

Disease Overview: Multiple myeloma accounts for approximately 10% of hematologic malignancies. Diagnosis: The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy‐proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hyper c alcemia, r enal failure, a nemia, or lytic b one lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging. Risk Stratification: The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high‐risk multiple myeloma. The presence of any two high risk factors is considered double‐hit myeloma, and three or more high risk factors is triple‐hit myeloma. Risk‐Adapted Initial Therapy: In patients who are candidates for autologous stem cell transplantation, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3–4 cycles followed by autologous stem cell transplantation (ASCT). In high‐risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara‐VRd) is an alternative to VRd. Selected standard‐risk patients can collect stem cells, get additional cycles of induction therapy, and delay transplant until first relapse. Patients who are not candidates for transplant are treated with VRd for approximately 8–12 cycles followed by maintenance or alternatively with daratumumab, lenalidomide, dexamethasone (DRd) until progression. Maintenance Therapy: Standard‐risk patients need lenalidomide maintenance, while bortezomib plus lenalidomide maintenance is needed for high‐risk myeloma. Management of Relapsed Disease: A triplet regimen is usually needed at relapse, with the choice of regimen varying with each successive relapse.

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  • There is a fraction of individuals with a genetic predisposition to develop multiple myeloma.

    “Finally, the idea that there is a fraction of individuals with a genetic predisposition to develop MM is further supported by two additional lines of evidence.”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [53]

    The Disease Overview (page unavailable) says that patients with certain cytogenetic abnormalities have a higher risk of progression from MGUS or smoldering myeloma to multiple myeloma. The Molecular Classification section (page unavailable) describes these as abnormalities in the plasma cells, including somatic changes. This supports a genetic influence on progression in a subset of patients, but not the broader claim that some individuals have an inherited predisposition to develop myeloma. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • Multiple myeloma can also occur in young adults.

    “However, this condition can also occur in young adults, likely reflecting a genetic predisposition, in line with patterns seen in other solid tumors.”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [53]

    The Disease Overview reports a median age at multiple myeloma diagnosis of about 65 years, but does not say whether it occurs in young adults. Searches for young patients and diagnoses under age 50 found no passage addressing that point; the reference to people aged 10–49 concerns MGUS, not multiple myeloma. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • Occurrence of multiple myeloma in young adults likely reflects a genetic predisposition.

    “However, this condition can also occur in young adults, likely reflecting a genetic predisposition, in line with patterns seen in other solid tumors.”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [53]

    The Disease Overview states that the median age at multiple myeloma diagnosis is about 65. The Molecular Classification section describes cytogenetic abnormalities in the disease, but does not link genetic predisposition to cases in young adults. Searches for young adults and inherited or familial susceptibility found no passage making that link; page numbers were unavailable in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Rajkumar, S. V.
Affiliations
Mayo Clinic (US)
Corresponding author
Rajkumar, S. Vincent
ORCID
Rajkumar, S. Vincent
Venue
American Journal of Hematology
Publisher
Wiley
Published
2022-05-23
Volume
97
Issue
8
Pages
1086-1107
ISSN
  • 0361-8609 (ISSN-L)
  • 1096-8652
DOI
10.1002/ajh.26590
PMC
PMC9387011
OpenAlex
W4280556871
Cited by
883
References
31
Citations by year
2026: 137 · 2025: 227 · 2024: 270 · 2023: 175 · 2022: 37 · 2021: 8 · 2020: 12 · 2019: 3 · 2018: 4 · 2017: 4 · 2015: 1 · 2013: 3
FWCI
129.08
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • American Journal of Hematology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (CA 168762, CA 186781)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Oncology › Bone health and treatments
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
Keywords
multiple myeloma, diagnosis, risk stratification, autologous stem cell transplantation, induction therapy, VRd, lenalidomide maintenance, bortezomib, daratumumab, relapsed multiple myeloma, maintenance therapy
MeSH terms
Bortezomib, Lenalidomide, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Humans, Multiple Myeloma, Neoplasm Recurrence, Local, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Risk Assessment

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