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Cited by 2,560CAR-T cell therapy researchMultiple Myeloma Research and TreatmentsProtein Degradation and Inhibitors

Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

Open access
Munshi, Nikhil C., Anderson, Larry D., Shah, Nina, Madduri, Deepu, Berdeja, Jesús, Lonial, Sagar, Raje, Noopur, Lin, Yi +20 more·2021·New England Journal of Medicine
DOI 10.1056/nejmoa2024850
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Abstract

BACKGROUND: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma. METHODS: CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses). RESULTS: nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion. CONCLUSIONS: Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).

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Crossref · 10.1056/nejmoa2024850

Cites

18 of 18 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 10 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The BCMA-directed CAR T cell ide-cel showed promising efficacy in a phase 1 study involving patients with relapsed or refractory myeloma.

    “The B-cell maturation antigen (BCMA)-directed CAR T cell idecabtagene vicleucel (ide-cel, also called bb2121) showed promising efficacy in a phase 1 study involving patients with relapsed or refractory myeloma.11”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] 11. Raje N, Berdeja J, Lin Y, et al. Anti- BCMA CAR T-cell therapy bb2121 in re- lapsed or refractory multiple myeloma. N Engl J Med 2019; 380: 1726-37. source
  • Interpretationcitation

    These efficacy results compare favorably with results in similarly heavily pretreated patients with relapsed or refractory myeloma treated with selinexor plus dexamethasone and belantamab mafodotin (median progression-free survival, 3.7 months and 2.9 months, respectively).

    “These efficacy results compare favorably with results in similarly heavily pretreated patients with relapsed or refractory myeloma treated with two recently approved regimens, selinexor plus dexamethasone and belantamab mafodotin (median progression-free survival, 3.7 months and 2.9 months, respectively).5,17”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [5] 5. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med 2019; 381: 727-38. source
    • cites [17] 17. Lonial S, Lee HC, Badros A, et al. Belan- tamab mafodotin for relapsed or refracto- ry multiple myeloma (DREAMM-2): a two- arm, randomised, open-label, phase 2 study. Lancet Oncol 2020; 21: 207-21. source
    • Rests on an assumption: Cross-trial comparisons of progression-free survival between the KarMMa study and trials of selinexor plus dexamethasone or belantamab mafodotin are valid.
  • Interpretationcitation

    Observed toxic effects were consistent with those in previous reports.

    “Observed toxic effects were consistent with those in previous reports.11”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] 11. Raje N, Berdeja J, Lin Y, et al. Anti- BCMA CAR T-cell therapy bb2121 in re- lapsed or refractory multiple myeloma. N Engl J Med 2019; 380: 1726-37. source

      The Results (Safety; page unavailable) document the observed toxic effects. The Discussion compares them with previous studies, but reports a lower incidence of severe cytokine release syndrome with bb2121 and cautions that cross-study comparisons are complicated. It does not establish that the toxic effects were generally consistent with previous reports. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Findingown data

    Clearance of sBCMA at month 2 was associated with longer progression-free survival.

    “Duration of undetectable sBCMA correlated with response duration, and clearance of sBCMA at month 2 was associated with longer progression-free survival (Fig. S5E and S5F).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Soluble BCMA is a serum-based universal marker of myeloma burden.
  • Findingown data

    Peak levels of proinflammatory markers were higher in patients having cytokine release syndrome of grade 3 or higher.

    “with peak levels higher in patients having cytokine release syndrome of grade 3 or higher (Fig. S6).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 12
  • May combine two claims. 32
  • The quote only partly states this claim. 1

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

    Premisecitation

    CD19 epitope loss is reported to be a relatively common escape mechanism after treatment with CD19-directed CAR T-cell therapy, especially in patients with acute leukemia.

    “In contrast, CD19 epitope loss is reported to be a relatively common escape mechanism after treatment with CD19-directed CAR T-cell therapy, especially in patients with acute leukemia.18,19”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [18] 18. Cheng J, Zhao L, Zhang Y, et al. Un- derstanding the mechanisms of resis- tance to CAR T-cell therapy in malignan- cies. Front Oncol 2019; 9: 1237. source

      The Tumor Factors section reports that loss of the targeted CD19 epitope enabled escape after anti-CD19 CAR T-cell therapy in relapsed B-ALL. It also reports that target-antigen-negative relapse accounts for approximately 9–25% of B-ALL relapses, but does not establish that epitope loss specifically is relatively common or more common in acute leukemia than in other malignancies. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [19] 19. Badar T, Shah NN. Chimeric antigen receptor T cell therapy for acute lympho- blastic leukemia. Curr Treat Options On- col 2020; 21: 16. source

  • May combine two claims.

    Findingown data

    Among patients with persistent grade 3 or 4 neutropenia or thrombocytopenia 1 month after infusion, median time to recovery to grade 2 or lower was 1.9 months and 2.1 months, respectively.

    “Among patients with persistent grade 3 or 4 neutropenia (52 patients) or thrombocytopenia (62 patients) 1 month after infusion, the median time to recovery to grade 2 or lower was 1.9 months (range, 1.2 to 5.6) and 2.1 months (range, 1.2 to 13.8), respectively”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Median progression-free survival was 12.1 months at the 450 × 10^6 dose and 20.2 months in patients with complete or stringent complete response.

    “The Kaplan-Meier estimated median progression-free survival was 8.8 months overall (95% CI, 5.6 to 11.6), 12.1 months (95% CI, 8.8 to 12.3) at the 450 × 10 6 dose, and 20.2 months (95% CI, 12.3 to could not be estimated) in patients having a complete or stringent complete response”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The 128 treated patients had received a median of 6 previous antimyeloma regimens, and 120 (94%) had received previous autologous hematopoietic stem-cell transplants.

    “The 128 treated patients had received a median of 6 previous antimyeloma regimens (range, 3 to 16), and 120 (94%) had received previous autologous hematopoietic stem-cell transplants (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    High interpatient variability was observed at all doses, and upper quartiles of exposure were observed more frequently at the 450 × 10^6 dose.

    “Although high interpatient variability was observed at all doses, upper quartiles of exposure (area under the curve of the transgene level from time of dose to 28 days [AUC 0-28 days ]) were observed more frequently at the 450 × 10 6 dose (Fig. 3B).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Among treated patients, 5 were positive for antidrug antibodies before infusion.

    “Among treated patients, 5 were positive for antidrug antibodies before infusion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Baseline sBCMA levels were elevated in treated patients and decreased rapidly after infusion in patients who had a response, with nadir values achieved within 3 months.

    “Baseline sBCMA levels were elevated in treated patients and de-creased rapidly after infusion in patients who had a response, with nadir values achieved within 3 months (Fig. 3A and Fig. S5B and S5C).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Soluble BCMA is a serum-based universal marker of myeloma burden.

  • May combine two claims.

    Findingown data

    Neurotoxic effects developed in 23 of 128 treated patients (18%) and were grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred.

    “Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred.”
    • Also stated in: § Table 1. (Continued.) · plain
      “Investigator-identified neurotoxic effects were reported in 23 patients (18%), of whom 4 (3%) had grade 3 events; no grade 4 or 5 neu-rotoxic effects were observed”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Median time to first response was 1.0 month, and median time to complete response or better was 2.8 months.

    “The median time to first response was 1.0 month (range, 0.5 to 8.8); the median time to a complete response or better was 2.8 months (range, 1.0 to 11.8).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At doses of 150, 300, and 450 × 10^6 CAR+ T cells, neurotoxic effects of any grade occurred in 0%, 17%, and 20%, and grade 3 events in 0%, 1%, and 6%, respectively.

    “At doses of 150 × 10 6 , 300 × 10 6 , and 450 × 10 6 CAR+ T cells, neurotoxic effects of any grade were reported in 0 of 4 patients, 12 of 70 patients (17%), and 11 of 54 patients (20%), respectively, with grade 3 events in 0 patients, 1 patient (1%), and 3 patients (6%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Antidrug antibodies had no effect on the incidence of response or of complete response or better.

    “Antidrug antibodies had no effect on the incidence of response or of complete response or better and had no noticeable effect on progression-free survival.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The absence of a detectable effect of antidrug antibodies on efficacy is not due to insufficient statistical power.

  • May combine two claims.

    Findingown data

    Median overall survival was 19.4 months, with 78% overall survival at 12 months.

    “The Kaplan-Meier estimated median overall survival was 19.4 months (95% CI, 18.2 to could not be estimated), with an overall survival of 78% at 12 months (Fig. 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Exposures were higher in patients who had a response than in those who did not, and higher exposure was associated with deeper response and longer progression-free survival.

    “Exposures were higher in patients who had a response than in those who did not (Fig. S5A), and higher exposure was associated with deeper response and longer progression-free survival (Fig. 3C and 3D).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Achievement of undetectable sBCMA levels increased with depth of response (17 of 27 [63%] with a partial response, 21 of 26 [81%] with a very good partial response, and 36 of 38 [95%] with a complete or stringent complete response).

    “Achievement of undetectable sBCMA levels increased with depth of response (17 of 27 pa-”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Soluble BCMA is a serum-based universal marker of myeloma burden.

  • May combine two claims.

    Findingown data

    At doses of 150, 300, and 450 × 10^6 CAR+ T cells, cytokine release syndrome of any grade occurred in 50%, 76%, and 96%, and grade 3 or higher in 0%, 6%, and 6%, respectively.

    “At doses of 150 × 10 6 , 300 × 10 6 , and 450 × 10 6 CAR+ T cells, cytokine release syndrome of any grade was observed in 2 of 4 patients (50%), 53 of 70 patients (76%), and 52 of 54 patients (96%), respectively, with cytokine release syndrome of grade 3 or higher observed in 0 patients, 4 patients (6%), and 3 patients (6%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Median duration of response was 10.7 months overall and 11.3 months at the 450 × 10^6 dose.

    “The Kaplan-Meier estimate for median duration of response was 10.7 months (95% CI, 9.0 to 11.3) overall and 11.3 months (95% CI, 10.3 to 11.4) at the 450 × 10 6 dose”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cytokine release syndrome was reported in 107 of 128 treated patients (84%), including 7 patients (5%) with grade 3 or higher events.

    “Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher.”
    • Also stated in: § Table 1. (Continued.) · plain
      “Cytokine release syndrome occurred in 107 patients (84%) and was mostly of grade 1 or 2 (Table 2 and Table S10).Five patients (4%) had grade 3 cytokine release syndrome, 1 (<1%) had grade 4, and 1 (<1%) had grade 5 (300 × 10 6 dose level).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Infections occurred in 88 patients (69%) and were grade 3 or 4 in 28 (22%).

    “Infections occurred in 88 patients (69%) and were of grade 3 or 4 in 28 (22%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Many patients had high tumor burden, high-risk cytogenetic abnormalities, and extramedullary disease.

    “including many with a high tumor burden, high-risk cytogenetic abnormalities, and extramedullary disease.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Common toxic effects among 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%).

    “Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After disease progression, 28 patients were retreated with ide-cel; 6 (21%) had a second response, with durations of 1.9 to 6.8 months, and all responders were retreated at a higher dose.

    “After disease progression, 28 patients were retreated with ide-cel (Table S4).Six patients (21%) had a second response, with durations of response ranging from 1.9 to 6.8 months; all the patients who had a response were retreated at a dose higher than their initial dose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most grade 3 or 4 events were hematologic toxic effects, including neutropenia in 114 patients (89%), anemia in 77 (60%), and thrombocytopenia in 67 (52%).

    “Most grade 3 or 4 events were hematologic toxic effects, including neutropenia in 114 patients (89%), anemia in 77 (60%), and thrombocytopenia in 67 (52%), and were at least partially related to the lymphodepleting chemotherapy administered before ide-cel infusion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A total of 44 treated patients (34%) died during the study, with most deaths (27) attributed to complications of myeloma progression.

    “A total of 44 treated patients (34%) died during the study, with most deaths (27) attributed by the investigator to complications of myeloma progression (Table S12).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Levels of proinflammatory markers, including cytokines, ferritin, and C-reactive protein, increased early after ide-cel infusion and decreased by month 1.

    “Levels of proinflammatory markers, including cytokines, ferritin, and C-reactive protein, increased early after ide-cel infusion and decreased by month 1”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Response duration increased with depth of response; median response duration was 4.5 months for partial response, 10.4 months for very good partial response, and 19.0 months for complete or stringent complete response.

    “The response duration increased with the depth of response; the median response duration was 4.5 months (95% CI, 2.9 to 6.7), 10.4 months (95% CI, 5.1 to 11.3), and 19.0 months (95% CI, 11.3 to could not be estimated) in patients having a best response of partial response (27 patients), very good partial response (25 patients), and complete or stringent complete response (42 patients),”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At target doses of 150, 300, and 450 × 10^6 CAR+ T cells, response was observed in 50%, 69%, and 81%, and complete response or better in 25%, 29%, and 39%, respectively.

    “At the target doses of 150 × 10 6 , 300 × 10 6 , and 450 × 10 6 CAR+ T cells, a response was observed in 2 of 4 patients (50%), in 48 of 70 patients (69%), and in 44 of 54 patients (81%), respectively, and a complete response or better was observed in 1 of 4 patients (25%), in 20 of 70 patients (29%), and in 21 of 54 patients (39%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Five patients (4%) died after 6 months from unrelated adverse events, and an additional 8 patients (6%) died after disease progression.

    “Five patients (4%) died after 6 months from unrelated adverse events, and an additional 8 patients (6%) died after disease progression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MRD-negative status (<10^-5 nucleated cells) was confirmed in 33 patients, representing 26% (95% CI, 19 to 34) of all 128 treated patients and 79% of the 42 patients with a complete or stringent complete response.

    “Minimal residual disease (MRD)-negative status (<10 -5 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better.”
    • Also stated in: § Efficacy · plain
      “Of the 42 patients with a complete or stringent complete response, 33 (79%) also had MRDnegative status at a sensitivity level of 10 -5 , corresponding to 26% (95% CI, 19 to 34) of the treated population; the remaining 9 patients (21%) could not be evaluated for MRD”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    High-grade hematologic toxic effects were common but transient.

    “High-grade hematologic toxic effects were common but transient.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    MRD-negative responses occurred in approximately a quarter of the patients, highlighting the depth of response induced by ide-cel.

    “The fact that MRDnegative responses occurred in approximately a quarter of the patients highlights the depth of response induced by ide-cel.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: MRD negativity at a sensitivity of 10^-5 is a valid measure of depth of response and clinical benefit.

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

    Study design and conductnone given

    The study protocol was approved by local or independent institutional review boards or ethics committees at participating sites, and all patients provided written informed consent.

    “The study protocol was approved by local or independent institutional review boards or ethics committees at participating sites.All the patients provided written informed consent.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Nearly all tumors expressed BCMA, a finding that supports the use of ide-cel in relapsed and refractory myeloma without restriction based on tumor BCMA expression.

    “Nearly all tumors expressed BCMA, a finding that supports the use of ide-cel in relapsed and refractory myeloma without restriction based on tumor BCMA expression.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: BCMA expression is required for ide-cel efficacy, so lack of tumor BCMA expression would limit its use.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The primary efficacy analysis was performed in the population of patients treated with ide-cel (128 patients).

    “The primary efficacy analysis was performed in the population of patients treated with ide-cel (128 patients).”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Of 140 patients enrolled, 128 received ide-cel infusions; 12 discontinued before infusion.

    “Between December 13, 2017, and November 13, 2018, a total of 140 patients were enrolled and underwent leukapheresis, of whom 128 received ide-cel infusions.Twelve patients discontinued the study before ide-cel infusion (including 1 patient who discontinued after unsuccessful manufacture of the CAR T-cell product)”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The study was designed by the authors in conjunction with the sponsors and conducted in accordance with ICH Good Clinical Practice guidelines and the principles of the Declaration of Helsinki.

    “The study was designed by the authors in conjunction with the sponsors and conducted in accordance with the International Council for Harmonisation guidelines for Good Clinical Practice and the principles of the Declaration of Helsinki.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The sample size for the primary end point was based on a one-sample binomial test with normal approximation, under the assumption of 15% dropout between enrollment and ide-cel treatment.

    “The sample size for the primary end point (overall response) was based on a onesample binomial test with normal approximation, under the assumption of 15% dropout between the time of enrollment and ide-cel treatment.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Statistical tests were not performed on subgroup analyses.

    “Statistical tests were not performed on subgroup analyses.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The primary end point was overall response (partial response or better), defined according to IMWG Uniform Response Criteria and assessed by an independent review committee.

    “The primary end point was an overall response (partial response or better), defined according to IMWG Uniform Response Criteria for Multiple Myeloma 12 as assessed by an independent review committee.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    MRD negativity was evaluated in bone marrow aspirates by next-generation sequencing (clonoSEQ, Adaptive Biotechnologies) with a minimum cutoff of 10^-5 nucleated cells.

    “MRD negativity was evaluated in bone marrow aspirates by next-generation sequencing (clonoSEQ, Adaptive Biotechnologies) with a minimum cutoff of 10 -5 nucleated cells.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The actual doses of ide-cel delivered were within 20% of the target doses.

    “The actual doses delivered were within 20% of the target doses.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    Adverse events were graded according to NCI CTCAE version 4.03, and cytokine release syndrome was graded according to published criteria.

    “Adverse events were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.Cytokine release syndrome was graded according to published criteria (Table S2).14”
    Quote in the paperNot a substantial claim
41 of 41

  • The paper relies on this without support.

    Soluble BCMA is a serum-based universal marker of myeloma burden.

    “Soluble BCMA was assessed as a serum-based universal marker of myeloma burden.”

  • The paper relies on this without support.

    Cross-trial comparisons of progression-free survival between the KarMMa study and trials of selinexor plus dexamethasone or belantamab mafodotin are valid.

    “These efficacy results compare favorably with results in similarly heavily pretreated patients with relapsed or refractory myeloma treated with two recently approved regimens, selinexor plus dexamethasone and belantamab mafodotin (median progression-free survival, 3.7 months and 2.9 months, respectively).5,17”

  • The paper relies on this without support.

    MRD negativity at a sensitivity of 10^-5 is a valid measure of depth of response and clinical benefit.

    “The fact that MRDnegative responses occurred in approximately a quarter of the patients highlights the depth of response induced by ide-cel.”

  • The paper relies on this without support.

    BCMA expression is required for ide-cel efficacy, so lack of tumor BCMA expression would limit its use.

    “Nearly all tumors expressed BCMA, a finding that supports the use of ide-cel in relapsed and refractory myeloma without restriction based on tumor BCMA expression.”

  • The paper relies on this without support.

    The absence of a detectable effect of antidrug antibodies on efficacy is not due to insufficient statistical power.

    “Antidrug antibodies had no effect on the incidence of response or of complete response or better and had no noticeable effect on progression-free survival.”
5 of 5

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?

  • 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”

    From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [89]

    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

  • Ide-cel safety profile remained consistent with prior reports, with no new safety signals, no additional CRS or iiNT events, and no parkinsonism, Guillain-Barré syndrome, or SPMs of T-cell origin reported.

    “Safety of ide-cel remained consistent with the IA, with no parkinsonism, Guillain-Barré syndrome, or SPMs of T-cell origin reported. 13”

    From Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. (2024) · cites this paper as [18]

    The Safety section and Table 2 report ide-cel adverse events in 128 treated patients, supporting the general reference to its safety profile. They do not compare these findings with a later analysis or state that no parkinsonism, Guillain-Barré syndrome, or T-cell–origin second primary malignancies were reported; Table 2 lists only adverse events occurring in at least 15% of patients. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Common side effects of Abecma such as CRS and ICANS were mostly low grade.

    “Common side effects such as CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were mostly low grade, indicating manageable toxicity.”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [243]

    Table 2 reports that CRS and investigator-identified neurotoxic effects were predominantly below grade 3, supporting the low-grade characterization. The Safety section also reports grade 3 or 4 adverse events in 99% of treated patients, so describing toxicity overall as manageable overstates what the low grades of these two effects establish. The paper calls the neurological events neurotoxic effects rather than explicitly identifying them as ICANS. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The median duration of response to Abecma was 11 months in patients achieving CR and 19 months in those achieving sCR.

    “The median duration of response (mDOR) was 11 months in patients achieving CR and 19 months in those achieving stringent complete response (sCR).”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [243]

    The Efficacy section reports a median response duration of 10.7 months overall (11.3 months at the highest dose), not 11 months specifically for patients achieving CR. It reports 19.0 months for patients achieving either CR or sCR combined, not for sCR alone. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • A number of BCMA-directed therapies, including belantamab mafodotin, idecabtagene vicleucel, ciltacabtagene autoleucel and teclistamab, have shown efficacy in clinical trials and are approved for treatment of relapsed or refractory multiple myeloma.

    “A number of BCMA-directed therapies, including belantamab mafodotin, idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel) and teclistamab, have shown efficacy in clinical trials and are approved for the treatment of relapsed or refractory multiple myeloma4–9.”

    From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [5]

    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

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Authors
Munshi, N. C., Anderson, L. D., Shah, N., Madduri, D., Berdeja, J., Lonial, S., Raje, N., Lin, Y., Siegel, D., Oriol, A., Moreau, P., Yakoub-Agha, I., Delforge, M., Cavo, M., Einsele, H., Goldschmidt, H., Weisel, K., Rambaldi, A., Reece, D., Petrocca, F., Massaro, M., Connarn, J. N., Kaiser, S., Patel, P., Huang, L., Campbell, T. B., Hege, K., & San-Miguel, J.
Affiliations
  • Harvard University (US)
  • Mayo Clinic (US)
  • Hackensack University Medical Center (US)
  • From the Jerome Lipper Multiple Myeloma Center, Dana–Farber Cancer Institute (N.C.M.), the Veterans Affairs Boston Healthcare System, Harvard Medical School (N.C.M.), and Massachusetts General Hospital (N.R.), Boston, and bluebird bio, Cambridge (F.P., M.M.) — all in Massachusetts; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas (L.D.A.); the University of California, San Francisco, San Francisco (N.S.); Icahn School of Medicine at Mount Sinai, New York ...
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2021-02-25
Volume
384
Issue
8
Pages
705-716
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2024850
OpenAlex
W3133229959
Semantic Scholar
fd96e2f87dff7d1153a17b78b56fbbab69cb714e
Cited by
2,560
References
17
Citations by year
2026: 411 · 2025: 486 · 2024: 540 · 2023: 493 · 2022: 436 · 2021: 186 · 2013: 2
FWCI
150.68
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, other-oa)
  • Lirias (KU Leuven) (submittedVersion)
Funders
Bristol-Myers Squibb
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
idecabtagene vicleucel, CAR T-cell therapy, relapsed/refractory multiple myeloma, BCMA, minimal residual disease, cytokine release syndrome, neurotoxicity, CAR T cell persistence, progression-free survival, complete response, neutropenia, anemia, thrombocytopenia, chimeric antigen receptor T cells
MeSH terms
Receptors, Chimeric Antigen, Progression-Free Survival, Cytokine Release Syndrome, Adult, Aged, Female, Hematologic Diseases, Humans, Male, Middle Aged, Multiple Myeloma, Recurrence, Biomarkers, Immunotherapy, Adoptive, Drug Resistance, Neoplasm

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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