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Cited by 1,445Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchMonoclonal and Polyclonal Antibodies Research

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Open access
Dimopoulos, Meletios A., Oriol, Albert, Nahi, Hareth, San-Miguel, Jesus, Bahlis, Nizar J., Usmani, Saad Z., Rabin, Neil, Orlowski, Robert Z. +16 more·2016·New England Journal of Medicine
DOI 10.1056/nejmoa1607751
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Abstract

BACKGROUND: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. RESULTS: white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. CONCLUSIONS: The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009 .).

Integrity signals

Registry

Crossref · 10.1056/nejmoa1607751

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

14 of 40 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The category of minimal residual disease status had not been examined to date in patients with relapsed or refractory multiple myeloma.

    “However, this category of minimal residual disease status has not been examined to date in patients with relapsed or refractory multiple myeloma, in part because of limited availability of data showing a correlation between depth of response and survival outcomes in patients at this stage of the disease.7”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [7] source

      The “Relapsed and/or refractory” section (page unavailable) says data linking depth of response to outcomes are limited, supporting the citing sentence’s rationale. The “Redefining CR” section discusses minimal residual disease (MRD) studies in newly diagnosed patients, but does not state that MRD status had never been examined in relapsed or refractory patients. The relapsed-setting section’s “MR” means minimal response, not minimal residual disease. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Premisecitation

    In the CASTOR trial, the addition of daratumumab to a standard-of-care regimen of bortezomib and dexamethasone was associated with a significantly lower risk of disease progression or death.

    “As in our trial (POLLUX), the addition of daratumumab to a standard-of-care regimen of bortezomib and dexamethasone in the CASTOR trial was associated with a significantly lower risk of disease progression or death.18”
    Quote in the paperNot a substantial claim1 of 1 sources checked
  • Interpretationcitation

    Daratumumab with lenalidomide and dexamethasone was associated with clinically manageable adverse events that were consistent with the known toxic effects of lenalidomide and dexamethasone and of daratumumab.

    “Daratumumab with lenalidomide and dexamethasone was associated with clinically manageable adverse events that were consistent with the known toxic effects of lenalidomide and dexamethasone 27,28,30,31 and of daratumumab.9,10”
    Quote in the paperSubstantial claim3 of 6 sources checked
    • cites [27] source
    • cites [28] source
    • cites [30] source
    • cites [31] source
    • cites [9] source
    • cites [10] source
  • Findingown data

    Similar overall response results were observed in the intention-to-treat population.

    “Similar results were observed in the intentionto-treat population (Table S3 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The rate of results below the threshold for minimal residual disease was significantly higher in the daratumumab group than in the control group by 3 to 5 times at all evaluated thresholds (1 tumor cell per 10^4, 10^5, and 10^6 white cells).

    “Consistent with the higher rates of deeper responses in the daratumumab group, the rate of results below the threshold for minimal residual disease was significantly higher in the daratumumab group than in the control group (by 3 to 5 times) at all evaluated thresholds (1 tumor cell per 10 4 , 10 5 , and 10 6 white cells) (Fig. S4 in the Supplementary Appendix).”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Premisecitation

    Daratumumab has shown substantial single-agent efficacy and a manageable safety profile in phase 1-2 studies involving patients with heavily pretreated relapsed or refractory multiple myeloma, with reported overall response rates of 29% and 36%.

    “Daratumumab, a human IgGκ monoclonal antibody that targets CD38, 8 has shown substantial single-agent efficacy and a manageable safety profile in phase 1-2 studies involving patients with heavily pretreated relapsed or refractory multiple myeloma, with reported overall response rates of 29% and 36%.9,10”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [9] source
    • cites [10] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

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

    Premisecitation

    Daratumumab is a human IgGκ monoclonal antibody that targets CD38.

    “Daratumumab, a human IgGκ monoclonal antibody that targets CD38, 8 has shown substantial single-agent efficacy and a manageable safety profile in phase 1-2 studies involving patients with heavily pretreated relapsed or refractory multiple myeloma, with reported overall response rates of 29% and 36%.9,10”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Study design and conductcitation

    Progression was determined with a validated computer algorithm that combined laboratory results and applicable imaging and generated the outcome according to IMWG criteria; this algorithm previously showed very strong concordance with independent reviews in a phase 2 study.

    “The primary end point was progression-free survival, with progression determined with the use of a validated computer algorithm that combined laboratory results (e.g., M-protein level) and applicable imaging and generated the outcome according to IMWG criteria (see the Supplementary Appendix).20,21 This algorithm previously showed very strong concordance with independent reviews in a phase 2 study”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [20] source
    • cites [21] source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [9] source

  • May combine two claims.

    Premisecitation

    A phase 3 trial of bortezomib and dexamethasone, with or without daratumumab, met its primary end point at the interim analysis and showed a significantly higher rate of progression-free survival, with a 61% lower risk of progression or death in the daratumumab group than in the control group.

    “A phase 3 trial of bortezomib and dexamethasone, with or without daratumumab, met its primary end point at the interim analysis and showed a significantly higher rate of progression-free survival, with a 61% lower risk of progression or death in the daratumumab group than in the control group.18”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    After the implementation of guidelines from other studies of daratumumab regarding the management of infusion-related reactions, infusion-related reactions were consistent with daratumumab monotherapy and combination therapy, were mostly of grade 1 or 2, and usually occurred during the first infusion.

    “After the implementation of guidelines from other studies of daratumumab regarding the management of infusion-related reactions, infusion-related reactions were consistent with daratumumab monotherapy 9,10 and combination therapy, 18,19,32 were mostly of grade 1 or 2, and usually occurred during the first infusion.”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [9] source
    • cites [10] source
    • cites [18] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [19] Plesner T, Blood

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

    • cites [32] Chari A, 2015, Blood source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Response was assessed according to the Uniform Criteria Consensus recommendations of the International Myeloma Working Group.

    “Response was assessed according to the Uniform Criteria Consensus recommendations of the International Myeloma Working Group.20,21”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [20] source
    • cites [21] source

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

    Premisecitation

    Daratumumab interferes with laboratory-based blood compatibility tests, including the indirect Coombs' test, because of binding to CD38 on red cells.

    “Daratumumab interferes with laboratory-based bloodcompatibility tests, including indirect Coombs' test, because of binding to CD38 on red cells.26”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Findingown data

    Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy.

    “Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Daratumumab-associated infusion-related reactions occurred in 47.7% of patients and were mostly of grade 1 or 2.

    “Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the time-to-event analysis of disease progression, 148 events were observed (44 patients [15.4%] in the daratumumab group vs. 104 [36.7%] in the control group), with a hazard ratio of 0.34 (95% CI, 0.23 to 0.48; P<0.001).

    “Similarly, in the time-toevent analysis of disease progression, a total of 148 events (in 44 patients [15.4%] in the daratumumab group vs. 104 [36.7%] in the control group) were observed (hazard ratio, 0.34; 95% CI, 0.23 to 0.48; P<0.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The rates of treatment discontinuation owing to adverse events were low and similar in the two groups (6.7% in the daratumumab group and 7.8% in the control group).

    “The percentage of patients with adverse events leading to the discontinuation of treatment was similar in the two groups: 6.7% in the daratumumab group and 7.8% in the control group.”
    • Also stated in: § Patients who have very good partial responses · plain
      “The rates of treatment discontinuation owing to adverse events were low and similar in the two groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The treatment effect of daratumumab was consistent regardless of previous exposure to lenalidomide and across all subgroups, including patients 65 years of age or older, those with disease refractory to proteasome inhibitors or the most recent line of therapy, those with International Staging System stage III disease, and those with previous exposure to a proteasome inhibitor or immunomodulatory药物

    “The treatment effect of daratumumab was consistent regardless of previous exposure to lenalidomide (a limitation being the relatively small number of patients with previous exposure to lenalidomide) and across all subgroups, including patients 65 years of age or older, those with disease that was refractory to proteasome inhibitors or the most recent line of therapy, those with International Stag”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although higher rates of neutropenia and infusion-related reactions were observed with daratumumab plus lenalidomide and dexamethasone than with lenalidomide and dexamethasone alone, these events did not result in higher rates of treatment discontinuation or death.

    “Although higher rates of neutropenia and infusion-related reactions (primarily during the first infusion) were observed with this combination than with lenalidomide and dexamethasone alone, these events did not result in higher rates of treatment discontinuation or death.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After continued treatment, responses deepened, with a rate of complete response or better that was twice as high with daratumumab as with the backbone regimen alone.

    “After continued treatment, responses deepened, with a rate of complete response or better that was twice as high with daratumumab as with the backbone regimen alone.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Infusion-related reactions were mostly of grade 1 or 2; 15 patients (5.3%) had grade 3 infusion reactions, and no patient had an event of grade 4 or 5.

    “These reactions were mostly of grade 1 or 2; a total of 15 patients (5.3%) had grade 3 infusion reactions, and no patient had an event of grade 4 or 5.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The overall response rate was 92.9% (95% CI, 89.2 to 95.6) in the daratumumab group and 76.4% (95% CI, 71.0 to 81.3) in the control group (P<0.001).

    “Overall response No. with response 261 211 -Rate -% (95% CI) 92.9 (89.2-95.6)76.4 (71.0-81.3)<0.001”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Serious adverse events were reported in 48.8% of patients in the daratumumab group and 42.0% of those in the control group; pneumonia was the most common (8.1% vs. 8.5%).

    “Serious adverse events were reported in 48.8% of the patients in the daratumumab group and in 42.0% of those in the control group, among which pneumonia was the most common (in 8.1% of the patients in the daratumumab group and in 8.5% of those in the control group).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The most common infection of grade 3 or 4 was pneumonia, which occurred at similar rates in the two groups.

    “The rate of infection of grade 3 or 4 was also slightly higher in the daratumumab group than in the control group (28.3% and 22.8%, respectively); the most common infection of grade 3 or 4 was pneumonia, which occurred at similar rates in the two groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The most common adverse events leading to death were acute kidney injury (0.4% daratumumab vs. 1.1% control), septic shock (1.1% vs. 0.4%), and pneumonia (0.7% in each group).

    “The most common adverse events leading to death were acute kidney injury (in 0.4% of the patients in the daratumumab group and in 1.1% in the control group), septic shock (in 1.1% and 0.4%, respectively), and pneumonia (in 0.7% in each group).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Incidences of grade 3 or 4 diarrhea, fatigue, nausea, and dyspnea were slightly higher in the daratumumab group than in the control group.

    “incidences of grade 3 or 4 diarrhea, fatigue, nausea, and dyspnea were slightly higher in the daratumumab group than in the control group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The rate of stringent complete response was 18.1% in the daratumumab group and 7.2% in the control group.

    “Stringent complete response § 51 (18.1) 20 (7.2) -”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The incidence of daratumumab infusion-related reactions of any grade was 47.7%, with 92% of the reactions occurring during the first infusion.

    “The incidence of daratumumab infusionrelated reactions of any grade was 47.7%, with 92% of the reactions occurring during the first infusion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The most common adverse events that led to discontinuation of treatment included pneumonia (1.1% daratumumab vs. 0.7% control), pulmonary embolism (1.1% control), and deterioration in general physical health (1.1% daratumumab).

    “The most common adverse events (in ≥1% of the patients in either group) that led to the discontinuation of treatment included pneumonia (in 1.1% of the patients in the daratumumab group and in 0.7% of those in the control group), pulmonary embolism (in 1.1% in the control group), and deterioration in general physical health (in 1.1% in the daratumumab group).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Despite higher rates of neutropenia in the daratumumab group, the rate of grade 3 or 4 infection was only slightly higher in the daratumumab group than in the control group (28% vs. 23%).

    “Despite higher rates of neutropenia in the daratumumab group, the rate of infection of grade 3 or 4 was only slightly higher in the daratumumab group than in the control group (28% vs. 23%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In our trial, the addition of daratumumab to the backbone regimen resulted in a significantly higher rate of overall response, deeper responses, and longer duration of response.

    “As in the CASTOR trial, 18 the addition of daratumumab to the backbone regimen in our trial resulted in a significantly higher rate of overall response, deeper responses, and longer duration of response.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most common infusion-related reactions were cough (8.5%), dyspnea (8.5%), and vomiting (5.7%).

    “The most common infusion-related reactions were cough (in 8.5% of the patients), dyspnea (in 8.5%), and vomiting (in 5.7%) (Table S5 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A phase 1-2 study of daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma showed that this combination provided therapeutic benefits, no dose-limiting toxic effects, and an 81% rate of overall response, including a 25% rate of stringent complete response.

    “A phase 1-2 study of daratumumab, lena-lidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma showed that this combination provided therapeutic benefits, no dose-limiting toxic effects, and an 81% rate of overall response, including a 25% rate of stringent complete response”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Plesner T, Blood

      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).

    Study design and conductnone given

    The group-sequential design had one planned interim analysis to evaluate the primary end point.

    “The group-sequential design had one planned interim analysis to evaluate the primary end point.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The incorporation of proteasome inhibitors and immunomodulatory drugs into the standard of care has improved outcomes in patients with multiple myeloma over the past 10 years.

    “he incorporation of proteasome inhibitors and immunomodulatory drugs into the standard of care has improved outcomes in patients with multiple myeloma over the past 10 years, [1][2][3]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1][2][3]

      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). May combine two claims.

    Study design and conductown data

    The trial was approved by the independent ethics committee or institutional review board at each site before initiation, patients provided written informed consent, and the trial was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice guidelines.

    “The trial was approved by the independent ethics committee or institutional review board at each site before the initiation of the trial.Patients provided written informed consent, and the trial was conducted in accordance with the principles of the Declaration of Helsinki and current International Conference on Harmonisation Good Clinical Practice guidelines.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    An independent data and safety monitoring committee was established to periodically review unblinded safety data.

    “An independent data and safety monitoring committee was established to periodically review unblinded safety data.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    At 18 months, the rate of progression-free survival was 72%, and the rate of overall survival was 90% in that phase 1-2 study.

    “At 18 months, the rate of progression-free survival was 72%, and the rate of overall survival was 90%.19”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Plesner T, Blood

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

  • May combine two claims.

    Study design and conductown data

    The most common reasons for discontinuation of treatment were progressive disease (14.1% in the daratumumab group vs. 34.2% in the control group) and adverse events (6.7% vs. 8.2%).

    “The most common reasons for the discontinuation of treatment were progressive disease (in 14.1% of the patients in the daratumumab group vs. 34.2% of those in the control group) and adverse events (in 6.7% vs. 8.2%) (Fig. S2 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The trial was calculated to need approximately 560 patients with 295 events to provide 85% power to detect a 30% lower risk of disease progression or death (hazard ratio, 0.70), using a log-rank test, with an overall two-sided significance level of 0.05.

    “We calculated that approximately 560 patients with 295 events (disease progression or death) would be needed to provide the trial with 85% power to detect a 30% lower risk of disease progression or death (hazard ratio, 0.70), using a log-rank test, with an overall two-sided significance level of 0.05.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Results below the threshold for minimal residual disease should be a treatment goal in the context of relapsed or refractory disease.

    “This suggests that results below the threshold for minimal residual disease also should be a treatment goal in the context of relapsed or refractory disease.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Subgroup analyses were prespecified.

    “Figure 2. Prespecified Subgroup Analyses.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Progression-free survival was analyzed in the intention-to-treat population, which included all patients who underwent randomization.

    “Shown are the results of the Kaplan-Meier analysis of progression-free survival among patients in the intention-totreat population, which included all patients who underwent randomization.”
    Quote in the paperSubstantial claim
37 of 37

  • The paper relies on this without support.

    Relapse can occur even after standard complete remission in the context of first-line therapy.

    “Relapse can occur even after standard complete remission in the context of first-line therapy, and studies are therefore evaluating deeper responses in a category termed “minimal residual disease-negative””

  • The paper relies on this without support.

    The combination of lenalidomide and dexamethasone is an appropriate standard control regimen for patients with relapsed or refractory multiple myeloma who have received one or more previous lines of therapy.

    “we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group).”

  • The paper relies on this without support.

    The open-label design does not bias the assessment of progression-free survival.

    “In this randomized, open-label, multicenter, phase 3 trial, we assigned patients who had relapsed or refractory multiple myeloma and had received one or more lines of previous therapy to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group) or lenalidomide and dexamethasone (control group).”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Daratumumab targets CD38 (a receptor highly expressed on myeloma cells) and has become a favorite for later line induction regimens.

    “The recently approved monoclonal antibody, daratumumab, which targets CD38 (a receptor highly expressed on myeloma cells), has become a favorite for later line induction regimens [35,36].”

    From Epidemiology, Staging, and Management of Multiple Myeloma (2021) · cites this paper as [36]

    The paper’s Efficacy section reports benefit from adding daratumumab for patients previously treated for multiple myeloma, and Table 3’s accompanying text describes its binding to CD38. Our copy does not establish that CD38 is highly expressed on myeloma cells or that daratumumab had become a favored later-line induction regimen. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Response rates to single-agent lenalidomide have consistently been surpassed by doublet or triplet combinations, which has been taken as evidence for synergistic activity of lenalidomide with other anti-myeloma agents.

    “Response rates to single-agent lenalidomide have consistently been surpassed by those achieved with doublet or triplet combinations, which has been taken as evidence for synergistic activity of this agent with other anti-myeloma agents48.”

    From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [48]

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.

  • Control-group adverse-event discontinuation rates differ

    Minor

    The results give 8.2% of control-group patients as discontinuing treatment because of adverse events, but the safety section gives 7.8% for adverse events leading to treatment discontinuation. The text does not explain the difference.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Krejcik J, Blood
  2. Plesner T, Blood

Cited by

Sorted by citations

Related

Authors
Dimopoulos, M. A., Oriol, A., Nahi, H., San-Miguel, J., Bahlis, N. J., Usmani, S. Z., Rabin, N., Orlowski, R. Z., Komarnicki, M., Suzuki, K., Plesner, T., Yoon, S.-S., Ben Yehuda, D., Richardson, P. G., Goldschmidt, H., Reece, D., Lisby, S., Khokhar, N. Z., O’Rourke, L., Chiu, C., Qin, X., Guckert, M., Ahmadi, T., & Moreau, P.
Affiliations
Karolinska University Hospital (SE)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2016-10-06
Volume
375
Issue
14
Pages
1319-1331
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1607751
OpenAlex
W2528329272
Cited by
1,445
References
32
Citations by year
2026: 50 · 2025: 78 · 2024: 78 · 2023: 108 · 2022: 138 · 2021: 221 · 2020: 236 · 2019: 175 · 2018: 193 · 2017: 148 · 2016: 15 · 2015: 1
FWCI
168.28
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, other-oa)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Funders
  • Amgen
  • Bristol-Myers Squibb
  • Spectrum Pharmaceuticals
  • Celgene
  • Incyte
  • Otsuka Pharmaceutical
  • Chugai Pharmaceutical
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
daratumumab, lenalidomide, dexamethasone, relapsed/refractory multiple myeloma, progression-free survival, minimal residual disease, complete response, neutropenia, thrombocytopenia, adverse events, monoclonal antibody therapy, combination therapy, overall response rate, safety and tolerability
MeSH terms
Lenalidomide, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Humans, Middle Aged, Multiple Myeloma, Recurrence, Thalidomide, Disease-Free Survival, Drug Resistance, Neoplasm, Kaplan-Meier Estimate

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 by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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