Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

In the paper

“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”

What the sources say

• ?Not checked — no full text of the sourcecites [9] source
• Partly supported

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

  cites [10] sourceExperimental — accuracy not yet measured

In the paper

“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”

What the sources say

• Supported

  The Ab generation section states that all antibodies described, including daratumumab, were human IgG1, κ antibodies. The Discussion identifies daratumumab as a human IgG1 antibody that binds CD38. The later phase 1–2 efficacy claims carry separate citations and are not attributed to this source. (LLM, conf=0.94)

  cites [8] source

In the paper

“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”

What the sources say

• ?Not checked — no full text of the sourcecites [20] source
• Partly supported

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

  cites [21] sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [9] source

In the paper

“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”

What the sources say

• Supported

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

  cites [18] source

In the paper

“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.”

What the sources say

• ?Not checked — no full text of the sourcecites [9] source
• Supported

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

  cites [10] source
• Partly supported

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

  cites [18] sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites [19] Plesner T, Blood
• ?Could not verify

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

  cites [32] Chari A, 2015, Blood sourceExperimental — accuracy not yet measured

In the paper

“Response was assessed according to the Uniform Criteria Consensus recommendations of the International Myeloma Working Group.20,21”

What the sources say

• ?Not checked — no full text of the sourcecites [20] source
• Supported

  The Response criteria section recommends using the IMWG uniform response criteria in clinical trials and says the panel endorsed their response definitions. The citation therefore supports the identification of the criteria used; it does not independently document how the citing study assessed response. (LLM, conf=0.93)

  cites [21] source

In the paper

“Daratumumab interferes with laboratory-based bloodcompatibility tests, including indirect Coombs' test, because of binding to CD38 on red cells.26”

What the sources say

• Supported

  The Discussion says daratumumab interferes with blood compatibility testing because it binds directly to CD38 on red cells. The “DARA causes plasma panreactivity in vitro” section reports panreactivity at the antihuman globulin phase, supporting the reference to the indirect Coombs test. (LLM, conf=0.93)

  cites [26] source

In the paper

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

In the paper

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

In the paper

“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).”

In the paper

“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.”

In the paper

“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”

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

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

In the paper

“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).”

In the paper

“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.”

In the paper

“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).”

In the paper

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

In the paper

“Stringent complete response § 51 (18.1) 20 (7.2) -”

In the paper

“The incidence of daratumumab infusionrelated reactions of any grade was 47.7%, with 92% of the reactions occurring during the first infusion.”

In the paper

“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).”

In the paper

“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%).”

In the paper

“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.”

In the paper

“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).”

In the paper

“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”

What the sources say

• ?Not matched

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

  cites [19] Plesner T, Blood

In the paper

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

In the paper

“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]”

What the sources say

• ?Not matched

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

  cites [1][2][3]

In the paper

“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.”

In the paper

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

In the paper

“At 18 months, the rate of progression-free survival was 72%, and the rate of overall survival was 90%.19”

What the sources say

• ?Not matched

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

  cites [19] Plesner T, Blood

In the paper

“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).”

In the paper

“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.”

In the paper

“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.”

In the paper

“Figure 2. Prespecified Subgroup Analyses.”

In the paper

“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.”