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Cited by 534Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchBone health and treatments

Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management

Open access
Rajkumar, S. Vincent·2024·American Journal of Hematology
DOI 10.1002/ajh.27422PMC PMC11404783
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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 (hypercalcemia, renal failure, anemia, or lytic bone 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 and urine monoclonal protein is ≥200 mg/24 h), 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, del 1p, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; 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 anti-CD38 monoclonal antibody plus bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT). Selected standard risk patients can delay transplant until first relapse. Frail patients who 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. Chimeric antigen receptor T (CAR-T) cell therapy and bispecific antibodies are additional options.

Integrity signals

Registry

Crossref · 10.1002/ajh.27422

Cites

199 of 199 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

54 of 148 cited sources checked · 27 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Teclistamab and elranatamab are BCMA-targeting bispecific antibodies approved for use in patients with relapsed myeloma who have received at least 4 prior regimens.

    “Two BCMA-targeting bispecific antibodies, teclistamab and elranatamab, have been approved for use in patients with relapsed myeloma who have received at least 4 prior regimens.91,92”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [91] source

      The Discussion explicitly says that no CD3-redirecting therapy had been approved for myeloma, contrary to the approval claim attributed to this paper. It confirms that teclistamab targets BCMA, but the Methods describe trial eligibility after at least three prior therapy lines, not an approval criterion of at least four regimens. Page numbers were not supplied in our copy. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [92]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    Overall survival in multiple myeloma is influenced by host characteristics, tumor burden, disease biology, and response to therapy.

    “As in other cancers, OS in multiple myeloma is affected by host characteristics, tumor burden (stage), biology (cytogenetic abnormalities), and response to therapy.48–50”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [48]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [49] source
    • cites [50]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    Tumor burden in multiple myeloma has traditionally been measured with the Durie-Salmon Staging and the International Staging System.

    “Tumor burden in multiple myeloma has traditionally been assessed using the Durie-Salmon Staging (DSS)51 and the International Staging System (ISS).52,53”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [51] source
    • cites [52] source
    • cites [53] source
  • Premisecitation

    For patients older than 75, median overall survival is about 5 years.

    “Among elderly patients (age >75 years), median OS is lower, and is approximately 5 years.46,47”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [46] source

      The Results report median overall survival of 63 months—about five years—for patients older than 75 receiving VRd. But the median was 31 months for patients in that age group receiving Rd, so the paper does not support an unqualified five-year median for all patients older than 75. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [47]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Premisecitation

    The serum free light chain assay is useful in patients without a measurable M protein when the FLC ratio is abnormal and involved FLC is at least 100 mg/L.

    “The serum FLC assay is particularly useful in patients who lack a measurable M protein, provided the FLC ratio is abnormal and the involved FLC level is ≥100 mg/L.34”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [34] source

      The Conclusion (page unavailable) says the FLC assay allows quantitative monitoring of patients with oligosecretory disorders, including some previously classified as nonsecretory myeloma. The AL amyloidosis section (page unavailable) uses an involved-FLC threshold greater than 10 mg per 100 ml (100 mg/L) to define response, but the passages do not establish the claimed combination of an abnormal ratio and ≥100 mg/L as a general condition for usefulness in patients without measurable M protein. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 8
  • May combine two claims. 38

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MGUS advances to multiple myeloma or a related malignancy at roughly 1% per year.

    “MGUS progresses to multiple myeloma or related malignancy a rate of 1% per year.16,17”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [16] source
    • cites [17] source

  • May combine two claims.

    Premisecitation

    Myeloma carries more than 400 canonical somatic mutations per patient, with common mutations in immunoglobulin heavy and light chain genes, NRAS, KRAS, and BRAF.

    “Studies show that myeloma is associated with more than 400 canonical somatic mutations per patient, and the most commonly mutated genes include immunoglobulin heavy chain and light chain genes, NRAS, KRAS and BRAF.43”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Idecabtagene vicleucel and ciltacabtagene autoleucel are BCMA-targeting CAR-T products active in relapsed refractory myeloma.

    “Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are newly approved CAR-T products targeting BCMA that are active in relapsed refractory myeloma.89,90”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [89] source

      The Abstract reports that ide-cel is a BCMA-directed CAR-T therapy active in relapsed or refractory myeloma, with responses in 94 of 128 treated patients. This paper does not establish that ide-cel was newly approved. It does not address cilta-cel, which the other citation in the sentence may cover. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [90]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bortezomib, carfilzomib, and ixazomib are proteasome inhibitors.

    “Bortezomib, carfilzomib, and ixazomib are proteasome inhibitors.81–83”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [81] source
    • cites [82]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [83] source

      The To the Editor section identifies bortezomib as an agent that inhibits the proteasome and explicitly calls carfilzomib a proteasome inhibitor. Our copy does not mention ixazomib, so it supports only two of the three identifications. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Elotuzumab targets SLAMF7, while daratumumab and isatuximab target CD38.

    “Elotuzumab targets SLAMF7; daratumumab and isatuximab target CD38 respectively.84–87”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [84] source
    • cites [85] source
    • cites [86]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [87]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In an ECOG randomized trial, low-dose dexamethasone was associated with better overall survival and significantly less toxicity.

    “In a randomized trial conducted by the Eastern Cooperative Oncology Group (ECOG), the low-dose dexamethasone approach was associated with superior OS and significantly lower toxicity.110”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    In the same trial, 8-year survival was lower for t(4;14) at 33% and for gain(1q) at 36%.

    “In contrast, survival was lower for patients with t(4;14) translocation (8-year survival rate, 33%) and for patients with gain(1q) abnormality (8-year survival rate, 36%).56”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [56] source

      The adverse-cytogenetics results (p. 5) report 96-month overall survival of 33% for patients with t(4;14) and 36% for patients with gain 1q21, but both figures are for the PAD arm, not the trial as a whole. The section also says cytogenetic results were based only on GMMG patients; the citing sentence omits these restrictions. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationreasoning

    These findings show limitations of current risk stratification under modern therapy and support stratifying myeloma by individual genomic groups rather than broad risk categories.

    “These findings underscore the limitations of current risk stratification models in the context of modern therapy and highlight the need to stratify multiple myeloma based on individual genomic groups rather than arbitrary heterogeneous risk categories.36,57”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [36] source
    • cites [57] source

  • May combine two claims.

    Premisecitation

    In a large trial with bortezomib-based induction, early ASCT, and bortezomib maintenance, patients with del(17p) had a median OS of about 8 years and an 8-year survival of 52%, identical to standard-risk patients.

    “In a large trial using bortezomib-based induction, early ASCT, and bortezomib maintenance, the median OS of patients with del(17p) was approximately 8 years (8-year survival rate of 52%), and was identical to patients with standard risk multiple myeloma.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [56] source

      The ‘Impact of study treatment on adverse cytogenetics’ section (p. 5) reports 96-month OS of 52% for PAD-treated patients with del(17p), versus 54% for those without it, supporting a similar 8-year survival rate. It does not report a median OS of approximately 8 years for the del(17p) subgroup, and the comparison group is patients without del(17p), not explicitly standard-risk patients. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Talquetamab is a bispecific antibody that binds GPRC5D on myeloma cells and CD3 on T cells.

    “Talquetamab is another novel bispecific antibody that binds to G protein–coupled receptor class C group 5 member D (GPRC5D) on myeloma cells and CD3 on T cells.93”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    In patients with relapsed multiple myeloma refractory to both lenalidomide and bortezomib, median progression-free survival is 5 months and median overall survival is 9 months.

    “The median PFS and OS in patients with relapsed multiple myeloma refractory to lenalidomide and bortezomib is poor, with median times of 5 months and 9 months, respectively.154”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [154] source

      The Results (Survival outcomes; page unavailable) report median event-free survival of 5 months and overall survival of 9 months for the entire cohort, not specifically for patients refractory to both lenalidomide and bortezomib. The Patients and Methods and Results show that the cohort also included patients whose IMiD was thalidomide and patients who had relapsed, were intolerant, or were ineligible for an IMiD. The reported 5-month measure is EFS, rather than the PFS named in the claim. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the ide-cel phase II trial, cytokine release syndrome occurred in 84% of patients, with 5% grade 3 or higher, and neurotoxicity occurred in 18%, with 3% grade 3.

    “Cytokine release syndrome was seen in 84%, and 5% were grade 3 or higher. Neurotoxicity was seen in 18%, and was grade 3 in 3%.”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    VRd, VCd, and VTd are active regimens in relapsed multiple myeloma.

    “As in newly diagnosed multiple myeloma, VRd, VCd, and VTd are active regimens in relapsed disease.164,165”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [164] source
    • cites [165] source

      The Efficacy section reports responses to lenalidomide plus bortezomib in relapsed or relapsed/refractory myeloma, and reports responses among patients who received added dexamethasone. The Discussion also cites preliminary activity for VRd in relapsed disease. The paper does not establish activity for VCd or VTd in relapsed disease. Passage-level page numbers were not provided. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Elotuzumab does not have single-agent activity but shows synergistic activity when combined with lenalidomide and dexamethasone (Rd).

    “Unlike daratumumab, elotuzumab does not have single-agent activity but shows synergistic activity when combined with Rd (Table 8).84”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [84] source

      The Efficacy section (page unavailable in our copy) reports higher response rates with elotuzumab plus lenalidomide and dexamethasone than with lenalidomide and dexamethasone alone. That supports a benefit from adding elotuzumab, but the paper does not assess elotuzumab alone or establish that the combination is synergistic; searches for monotherapy and synergy found no such passage. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Once-weekly carfilzomib at 56 to 70 mg/m2 may be equally effective and safe as twice-weekly 27 mg/m2, and is more convenient.

    “Carfilzomib is typically administered twice-weekly at a dose of 27 mg/m2 (refer to Table 6), but a once-weekly schedule of 56 to 70 mg/m2 may be equally effective and safe, and more convenient.168”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [168] source

      The Introduction reports that a study of once-weekly 70 mg/m² versus twice-weekly 27 mg/m² found better efficacy with similar rates of severe adverse events. The Discussion says once-weekly dosing would reduce clinic visits. However, this paper’s pooled analysis compares 70 mg/m² once weekly with 36 mg/m² twice weekly; the cited passages do not establish comparable efficacy and safety for once-weekly 56 mg/m² versus twice-weekly 27 mg/m². Page numbers are unavailable in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In a phase II trial of 128 patients with relapsed refractory myeloma, ide-cel produced a response rate of 73%, with 33% achieving complete response or better, and a median progression-free survival of 8.8 months.

    “Among 128 patients with relapsed refractory myeloma treated on a phase II trial, ide-cel was associated with a response rate of 73%.89 Thirty three percent of patients had a complete response or better. The median PFS was 8.8 months.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Ixazomib is active in both the relapsed refractory setting and in newly diagnosed multiple myeloma.

    “Ixazomib is an oral proteasome inhibitor that is active in both the relapsed refractory setting and in newly diagnosed multiple myeloma.73,174”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [73] source
    • cites [174]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Early studies in SMM failed to show an advantage to preventive intervention, but were limited by lack of power, safe and effective drugs, and a risk-adapted strategy.

    “Early studies in SMM failed to show an advantage to preventive intervention, but were limited by lack of power, safe and effective drugs, and a risk-adapted strategy.195,196”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [195] source
    • cites [196] source

      The Materials and methods passage (p. 1102) reports no significant survival advantage for melphalan plus prednisone over no treatment in stage I multiple myeloma. The Discussion (p. 1104) describes ineffective therapies and inadequate prognostic tools for guiding treatment. The paper does not identify its stage I patients as having SMM or establish that the early trials lacked statistical power or safe drugs. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    About 40% of multiple myeloma is hyperdiploid with trisomies, while most of the remainder has an IgH translocation.

    “Approximately 40% of multiple myeloma is characterized by the presence of trisomies in the neoplastic plasma cells (hyperdiploid multiple myeloma), while most of the rest have a translocation involving the immunoglobulin heavy chain (IgH) locus on chromosome 14q32 (IgH translocated multiple myeloma).38–41”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [38] source
    • cites [39] source
    • cites [40] source
    • cites [41] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Belantamab mafodotin is a humanized anti-BCMA antibody conjugated to monomethyl auristatin-F, a microtubule disruptor.

    “Belantamab mafodotin is a humanized antibody targeting B cell maturation agent (BCMA) that is conjugated to monomethyl auristatin-F, a microtubule disrupting agent.88”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Dara-VRd gives better response rates, MRD negativity rates, and progression-free survival than VRd.

    “Response rates, MRD negative rates, and progression free survival (PFS) are superior with Dara-VRd when compared to bortezomib, lenalidomide, and dexamethasone (VRd) (Table 7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the IFM trial, early ASCT significantly improved PFS, but at 8 years overall survival was 60% with delayed ASCT and 62% with early ASCT.

    “Updated results from the Intergroupe Francophone du Myelome (IFM) trial continued to show a significant improvement in PFS with early ASCT, but at 8years, OS was 60% in the delayed ASCT groups and 62% in the early ASCT group.95”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [95]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Bortezomib neurotoxicity can be greatly reduced by giving it once weekly instead of twice weekly and subcutaneously instead of intravenously.

    “However, the neurotoxicity of bortezomib can be greatly diminished by administering bortezomib once a week instead of twice-weekly,116,117 and by administering the drug subcutaneously instead of the intravenous route.118”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [116] source
    • cites [117] source
    • cites [118]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Recent data show that quadruplet regimens give better response rates, MRD negativity rates, and progression-free survival than triplets even in patients over 65.

    “Recent data show that response rates, MRD negative rates, and progression free survival (PFS) are superior with quadruplet regimens compared to triplets even in patients over the age of 65 (Table 7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    MRD negativity, assessed by next-generation molecular methods or flow cytometry, has favorable prognostic value and may serve as a surrogate endpoint in myeloma trials.

    “Recent data show that MRD negative status (as estimated by next generation molecular methods or flow cytometry) has favorable prognostic value and may be of value as a surrogate endpoint for clinical trials in myeloma.35,108,109”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [35]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [108] source
    • cites [109] source

  • May combine two claims.

    Premisecitation

    Once-weekly subcutaneous bortezomib is now standard and has made serious neuropathy less frequent.

    “The once-weekly subcutaneous bortezomib schedule is now the standard (Table 6), and has made serious neuropathy a less frequent problem.119”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The treatment-related mortality rate for allogeneic transplantation is 10-20%, and GVHD rates are fairly high.

    “The treatment related mortality (TRM) rate (10–20%) and GVHD rates are fairly high.141”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [141]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    The BMT-CTN 0702 trial specifically isolated the effect of consolidation, making it more compelling than earlier trials that could not determine the precise added value of consolidation on PFS and OS.

    “Unlike earlier trials, the BMT-CTN 0702 trial specifically isolated the effect of consolidation and is therefore more compelling than trials where one could not ascertain the precise added value of consolidation therapy on PFS and OS.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Pomalidomide-containing triplet regimens such as daratumumab, pomalidomide, dexamethasone (DPd) and carfilzomib, pomalidomide, dexamethasone (KPd) are important options at relapse for patients who are considered lenalidomide-refractory.

    “Pomalidomide-containing triplet regimens such as daratumumab, pomalidomide, dexamethasone (DPd) and carfilzomib, pomalidomide, dexamethasone (KPd) are important options at relapse for patients who are considered lenalidomide-refractory (Table 8).71,173”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [71]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [173]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Bortezomib administered every other week improves overall survival, particularly in patients with del(17p).

    “Bortezomib administered every other week has been shown to improve OS, particularly in patients with del(17p).145”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [145] source

  • May combine two claims.

    Premisecitation

    The KRd regimen has been shown to be effective in a randomized trial and is a major option for the treatment of relapsed multiple myeloma.

    “The KRd regimen has been shown to be effective in a randomized trial, and is a major option for the treatment of relapsed disease (Table 8).67”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] source

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Based on these results, delayed ASCT is reasonable at least for standard-risk patients who prefer it for personal and logistic reasons.

    “Based on these results, it is reasonable to consider a delayed ASCT at least in patients with standard-risk multiple myeloma who prefer such an approach for personal and logistic reasons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Current clinical practice typically involves patients who have been treated with lenalidomide and are often relapsing while on a lenalidomide-containing regimen.

    “In contrast, current clinical practice typically consists of patients who have been treated with lenalidomide and are often relapsing while on a lenalidomide-containing regimen.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Patients with SMM have a risk of progression of approximately 10% per year for the first 5 years, 3% per year for the next 5 years, and 1% per year thereafter.

    “Patients with SMM have a risk of progression of approximately 10% per year for the first 5 years, 3% per year for the next 5 years, and 1% per year thereafter.19”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Denosumab is an alternative to bisphosphonates, especially in patients with significant renal dysfunction.

    “Denosumab, a high-affinity monoclonal antibody targeting RANKL is an alternative especially in patients with significant renal dysfunction.189”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Smoldering multiple myeloma (SMM) is a stage clinically positioned between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma.

    “SMM is a stage that is clinically positioned between MGUS and multiple myeloma.192”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [192]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The presence of 2 or 3 risk factors is associated with a median time to progression to multiple myeloma of approximately 2 years, and is considered high risk SMM.

    “Presence of 2 or 3 of these factors is associated with a median TTP to multiple myeloma of approximately 2 years, and is considered high risk SMM (Mayo 2018 criteria).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Bispecific antibodies can be administered rapidly in patients with aggressive relapse, unlike CAR-T cell products which require several weeks for collection, manufacture, and administration.

    “Bispecific antibodies can be administered rapidly in patients with aggressive relapse unlike CAR-T cell products which require several weeks of time for collection, manufacture, and administration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Teclistamab and elranatamab have shown significant activity as single agents, with an overall response rate approximately double that previously seen with earlier myeloma agents, with the exception of CAR-T cell therapy.

    “Both have shown significant activity as single agents, with overall response rate approximately double that previously seen with earlier myeloma agents with the exception of CAR-T cell therapy (Table 9).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    An initial randomized trial of belantamab mafodotin did not show significant benefit, and the drug was taken off the market.

    “Unfortunately the development of keratopathy results frequently in disruption of therapy after 2 doses limiting the efficacy and feasibility of this treatment, and an initial randomized trial did not show significant benefit, and hence the drug has been taken of the market.161”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [161]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In the cilta-cel phase II study, cytokine release syndrome occurred in 95% of patients, with 4% grade 3-4, and neurotoxicity occurred in 21%, with 9% grade 3-4 severity.

    “Cytokine release syndrome occurred in 95%, and were grade 3–4 in 4%. Neurotoxicity occurred in 21%, and were grade 3–4 severity in 9%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In the initial phase II study of 97 patients with relapsed refractory multiple myeloma, cilta-cel produced an overall response rate of 97%, with 67% achieving stringent complete response, and 12-month progression-free survival and overall survival of 77% and 89%, respectively.

    “In the initial phase II study of 97 patients with relapsed refractory multiple myeloma, the overall response rate was 97% with 67% achieving stringent complete response.90 The 12-month PFS and OS were 77% and 89%, respectively.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [90]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Myeloma patients do not respond adequately to COVID vaccines and need boosters as recommended.

    “Myeloma patients do not respond adequate to COVID vaccines and need boosters as recommended.191”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [191] source

  • May combine two claims.

    Premisereasoning

    Talquetamab is a bispecific antibody that targets GPRC5D and can therefore be valuable even in patients who have been previously treated with BCMA-directed therapy.

    “Talquetamab, is a bispecific antibody that targets GPRC5D and can hence be valuable even in patients who have been previously treated with BCMA directed therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Within the current definition of SMM, there are two groups of patients: high risk (25% per year risk of progression in the first 2 years) and low risk (~5% per year risk of progression).

    “Within the current definition of SMM (Table 1), there are two groups of patients: high risk (25% per year risk of progression in the first 2 years) and low risk (~ 5% per year risk of progression).192”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [192]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

45 of 45

  • The paper relies on this without support.

    Smoldering multiple myeloma progresses to multiple myeloma at about 10% per year in the first five years after diagnosis, 3% per year in the next five years, and 1.5% per year thereafter.

    “SMM is prevalent in approximately 0.5% of the general population 40 years of age or older,20 and progresses to multiple myeloma at a rate of approximately 10% per year over the first 5 years following diagnosis, 3% per year over the next 5 years, and 1.5% per year thereafter.”

  • The paper relies on this without support.

    Most patients in the trial who were considered transplant ineligible because of age 65–70 would be considered transplant candidates in the United States.

    “However, most patients considered transplant ineligible in this trial (age 65–70), will be considered transplant candidates in the US.”

  • The paper relies on this without support.

    Almost all patients with multiple myeloma eventually relapse.

    “Almost all patients with multiple myeloma eventually relapse.”

  • The paper relies on this without support.

    Most patients eventually become refractory to all drug classes.

    “Despite the multiple options available, most patients eventually become refractory to all drug classes.”

  • The paper relies on this without support.

    Lenalidomide maintenance is associated with a 2–3 fold increase in the risk of second cancers.

    “Lenalidomide maintenance is associated with a 2–3 fold increase in the risk of second cancers and patients must be counseled in this regard and monitored.”

  • The paper relies on this without support.

    Many patients seek a drug-free interval.

    “Many patients seek a drug-free interval.”

  • The paper relies on this without support.

    The dosing of bispecific antibodies is not yet optimized.

    “The dosing of bispecific antibodies is not yet optimized, and is likely that abbreviated dosing schedules may produce durable remissions and less toxicity.”
7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting long-term progression rates for smoldering myeloma

    Minor

    The disease overview gives the annual progression rate after the first 10 years as 1.5%, while the smoldering myeloma section gives it as 1%.

1 of 1

Cites

Flagged first, then by citations

2 of the 201 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Facon T, 1996, Front‐line or rescue autologous bone marrow transplantation (ABMT) following a first course of high dose melphalan (HDM) in multiple myeloma (MM). Preliminary results of a prospective randomized trial (CIAM) protocol, Blood, 88
  2. Fermand JP, 2003, Single versus tandem high dose therapy (HDT) supported with autologous blood stem cell (ABSC) transplantation using unselected or CD34‐enriched ABSC: results of a two by two designed randomized trial in 230 young patients with multiple myeloma (MM), Hematol J, 4, S59
  3. Goldschmidt H, 2003, Single vs. tandem autolgous transplantation in multiple myeloma: the GMMG experience, Hematol J, 4, S61

Cited by

Sorted by citations

Related

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
2024-06-28
Volume
99
Issue
9
Pages
1802-1824
ISSN
  • 0361-8609 (ISSN-L)
  • 1096-8652
DOI
10.1002/ajh.27422
PMC
PMC11404783
OpenAlex
W4400157075
Cited by
534
References
201
Citations by year
2026: 276 · 2025: 242 · 2024: 15 · 2020: 1
FWCI
42.29
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)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
National Institutes of Health (CA168762, CA186781)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
multiple myeloma, diagnosis, risk stratification, autologous stem cell transplantation, lenalidomide maintenance, bortezomib, anti-CD38 monoclonal antibody, 17p deletion, TP53 mutation, relapsed multiple myeloma, CAR T-cell therapy, bispecific antibodies, monoclonal immunoglobulin light chains, plasmacytoma
MeSH terms
Antineoplastic Combined Chemotherapy Protocols, Humans, Multiple Myeloma, Risk Factors, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Risk Assessment, Disease Management

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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