Study reading
Daratumumab combination produced more deep treatment responses
Patients with newly diagnosed multiple myeloma who were not having an initial transplant received a combination including daratumumab or the comparison combination without it. More patients receiving daratumumab reached complete response or better and tested negative for minimal residual disease. These responses were more often sustained, while progression-free survival among patients testing negative showed only a nonsignificant trend favoring daratumumab. The trial enrolled patients who were transplant-ineligible or deferred transplant as initial therapy, so it does not establish the same result for all newly diagnosed patients. Among patients who achieved minimal-residual-disease negativity, the progression-free-survival difference was not statistically significant, so an advantage in that subgroup remains uncertain. The median follow-up was 58.7 months, so outcomes beyond that period are not established.
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Patients with newly diagnosed multiple myeloma who were not having an initial transplant received a combination including daratumumab or the comparison combination without it. More patients receiving daratumumab reached complete response or better and tested negative for minimal residual disease. These responses were more often sustained, while progression-free survival among patients testing negative showed only a nonsignificant trend favoring daratumumab.
What the study found
Patients with newly diagnosed multiple myeloma who were not having an initial transplant received a combination including daratumumab or the comparison combination without it. More patients receiving daratumumab reached complete response or better and tested negative for minimal residual disease. These responses were more often sustained, while progression-free survival among patients testing negative showed only a nonsignificant trend favoring daratumumab. Source ↗
With median follow-up of 58.7 months, overall minimal-residual-disease negativity at the 10-5 threshold was 60.9% with D-VRd and 39.4% with VRd. Source ↗
Who and what was studied
Patients with newly diagnosed multiple myeloma who were transplant-ineligible or deferred transplant as initial therapy. Source ↗
D-VRd, containing daratumumab, bortezomib, lenalidomide and dexamethasone, was compared with VRd. Source ↗
What remains uncertain
The trial enrolled patients who were transplant-ineligible or deferred transplant as initial therapy, so it does not establish the same result for all newly diagnosed patients. Among patients who achieved minimal-residual-disease negativity, the progression-free-survival difference was not statistically significant, so an advantage in that subgroup remains uncertain. The median follow-up was 58.7 months, so outcomes beyond that period are not established. Source ↗
Follow the evidence.
Source links and automated passage checks do not establish clinical review.
Supporting passages: Daratumumab combination produced more deep treatment responses
In the phase 3 CEPHEUS study, D-VRd (daratumumab/bortezomib/lenalidomide/dexamethasone) increased overall minimal residual disease (MRD)-negativity rates vs VRd in patients who were transplant ineligible/deferred with newly diagnosed multiple myeloma (NDMM). We present an expanded MRD analysis of CEPHEUS. Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd. Overall MRD negativity (next-generation sequencing) was defined as the proportion of patients achieving complete response or better and MRD-negative status assessed at 10-5 (primary end point) and 10-6 thresholds. In total, 395 patients were randomized (D-VRd, n = 197; VRd, n = 198). With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd vs VRd (10-5: 60.9% vs 39.4%; odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P< .0001; 10-6: 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P = .0001). Sustained MRD negativity (≥12 months) was significantly higher with D-VRd vs VRd (10-5: 49.2% vs 27.3%; 10-6: 34.0% vs 16.2%; each P< .0001), with similar benefits at ≥24 and ≥36 months. MRD-negativity rates were higher at all prespecified time points and cumulatively with D-VRd. Among patients who achieved MRD negativity, progression-free survival (PFS) trended in favor of D-VRd vs VRd (10-5: hazard ratio, 0.61; 95% CI, 0.35-1.06; P = .0755; 10-6: 0.66; 95% CI, 0.31-1.41; P = .2811). Responses with D-VRd were deeper and more durable vs VRd, with increased overall, sustained, and landmark MRD-negativity rates, translating into improved overall PFS with D-VRd vs VRd (intent-to-treat), with potential to improve PFS even among patients with MRD negativity. D-VRd is therefore a new standard-of-care treatment for transplant-ineligible/transplant-deferred NDMM. This trial was registered at www.clinicaltrials.gov as NCT03652064.
PMID 42234958 · abstract-1
Supporting passages: Patients with newly diagnosed multiple myeloma who were not having an initial transplant received a combination including daratumumab or the comparison combination without it. More patients receiving daratumumab reached complete response or better and tested negative for minimal residual disease. These responses were more often sustained, while progression-free survival among patients testing negative showed only a nonsignificant trend favoring daratumumab. The trial enrolled patients who were transplant-ineligible or deferred transplant as initial therapy, so it does not establish the same result for all newly diagnosed patients. Among patients who achieved minimal-residual-disease negativity, the progression-free-survival difference was not statistically significant, so an advantage in that subgroup remains uncertain. The median follow-up was 58.7 months, so outcomes beyond that period are not established.
In the phase 3 CEPHEUS study, D-VRd (daratumumab/bortezomib/lenalidomide/dexamethasone) increased overall minimal residual disease (MRD)-negativity rates vs VRd in patients who were transplant ineligible/deferred with newly diagnosed multiple myeloma (NDMM). We present an expanded MRD analysis of CEPHEUS. Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd. Overall MRD negativity (next-generation sequencing) was defined as the proportion of patients achieving complete response or better and MRD-negative status assessed at 10-5 (primary end point) and 10-6 thresholds. In total, 395 patients were randomized (D-VRd, n = 197; VRd, n = 198). With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd vs VRd (10-5: 60.9% vs 39.4%; odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P< .0001; 10-6: 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P = .0001). Sustained MRD negativity (≥12 months) was significantly higher with D-VRd vs VRd (10-5: 49.2% vs 27.3%; 10-6: 34.0% vs 16.2%; each P< .0001), with similar benefits at ≥24 and ≥36 months. MRD-negativity rates were higher at all prespecified time points and cumulatively with D-VRd. Among patients who achieved MRD negativity, progression-free survival (PFS) trended in favor of D-VRd vs VRd (10-5: hazard ratio, 0.61; 95% CI, 0.35-1.06; P = .0755; 10-6: 0.66; 95% CI, 0.31-1.41; P = .2811). Responses with D-VRd were deeper and more durable vs VRd, with increased overall, sustained, and landmark MRD-negativity rates, translating into improved overall PFS with D-VRd vs VRd (intent-to-treat), with potential to improve PFS even among patients with MRD negativity. D-VRd is therefore a new standard-of-care treatment for transplant-ineligible/transplant-deferred NDMM. This trial was registered at www.clinicaltrials.gov as NCT03652064.
PMID 42234958 · abstract-1
Supporting passages: Patients with newly diagnosed multiple myeloma who were not having an initial transplant received a combination including daratumumab or the comparison combination without it. More patients receiving daratumumab reached complete response or better and tested negative for minimal residual disease. These responses were more often sustained, while progression-free survival among patients testing negative showed only a nonsignificant trend favoring daratumumab.
In the phase 3 CEPHEUS study, D-VRd (daratumumab/bortezomib/lenalidomide/dexamethasone) increased overall minimal residual disease (MRD)-negativity rates vs VRd in patients who were transplant ineligible/deferred with newly diagnosed multiple myeloma (NDMM). We present an expanded MRD analysis of CEPHEUS. Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd. Overall MRD negativity (next-generation sequencing) was defined as the proportion of patients achieving complete response or better and MRD-negative status assessed at 10-5 (primary end point) and 10-6 thresholds. In total, 395 patients were randomized (D-VRd, n = 197; VRd, n = 198). With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd vs VRd (10-5: 60.9% vs 39.4%; odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P< .0001; 10-6: 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P = .0001). Sustained MRD negativity (≥12 months) was significantly higher with D-VRd vs VRd (10-5: 49.2% vs 27.3%; 10-6: 34.0% vs 16.2%; each P< .0001), with similar benefits at ≥24 and ≥36 months. MRD-negativity rates were higher at all prespecified time points and cumulatively with D-VRd. Among patients who achieved MRD negativity, progression-free survival (PFS) trended in favor of D-VRd vs VRd (10-5: hazard ratio, 0.61; 95% CI, 0.35-1.06; P = .0755; 10-6: 0.66; 95% CI, 0.31-1.41; P = .2811). Responses with D-VRd were deeper and more durable vs VRd, with increased overall, sustained, and landmark MRD-negativity rates, translating into improved overall PFS with D-VRd vs VRd (intent-to-treat), with potential to improve PFS even among patients with MRD negativity. D-VRd is therefore a new standard-of-care treatment for transplant-ineligible/transplant-deferred NDMM. This trial was registered at www.clinicaltrials.gov as NCT03652064.
PMID 42234958 · abstract-1
Supporting passages: Patients with newly diagnosed multiple myeloma who were not having an initial transplant received a combination including daratumumab or the comparison combination without it. More patients receiving daratumumab reached complete response or better and tested negative for minimal residual disease. These responses were more often sustained, while progression-free survival among patients testing negative showed only a nonsignificant trend favoring daratumumab.
In the phase 3 CEPHEUS study, D-VRd (daratumumab/bortezomib/lenalidomide/dexamethasone) increased overall minimal residual disease (MRD)-negativity rates vs VRd in patients who were transplant ineligible/deferred with newly diagnosed multiple myeloma (NDMM). We present an expanded MRD analysis of CEPHEUS. Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd. Overall MRD negativity (next-generation sequencing) was defined as the proportion of patients achieving complete response or better and MRD-negative status assessed at 10-5 (primary end point) and 10-6 thresholds. In total, 395 patients were randomized (D-VRd, n = 197; VRd, n = 198). With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd vs VRd (10-5: 60.9% vs 39.4%; odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P< .0001; 10-6: 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P = .0001). Sustained MRD negativity (≥12 months) was significantly higher with D-VRd vs VRd (10-5: 49.2% vs 27.3%; 10-6: 34.0% vs 16.2%; each P< .0001), with similar benefits at ≥24 and ≥36 months. MRD-negativity rates were higher at all prespecified time points and cumulatively with D-VRd. Among patients who achieved MRD negativity, progression-free survival (PFS) trended in favor of D-VRd vs VRd (10-5: hazard ratio, 0.61; 95% CI, 0.35-1.06; P = .0755; 10-6: 0.66; 95% CI, 0.31-1.41; P = .2811). Responses with D-VRd were deeper and more durable vs VRd, with increased overall, sustained, and landmark MRD-negativity rates, translating into improved overall PFS with D-VRd vs VRd (intent-to-treat), with potential to improve PFS even among patients with MRD negativity. D-VRd is therefore a new standard-of-care treatment for transplant-ineligible/transplant-deferred NDMM. This trial was registered at www.clinicaltrials.gov as NCT03652064.
PMID 42234958 · abstract-1
Supporting passages: With median follow-up of 58.7 months, overall minimal-residual-disease negativity at the 10-5 threshold was 60.9% with D-VRd and 39.4% with VRd.
Overall MRD negativity (next-generation sequencing) was defined as the proportion of patients achieving complete response or better and MRD-negative status assessed at 10-5 (primary end point) and 10-6 thresholds.
PMID 42234958 · abstract-1
With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd vs VRd (10-5: 60.9% vs 39.4%; odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P< .0001; 10-6: 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P = .0001).
PMID 42234958 · abstract-1
Supporting passages: Patients with newly diagnosed multiple myeloma who were transplant-ineligible or deferred transplant as initial therapy.
Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd.
PMID 42234958 · abstract-1
Supporting passages: D-VRd, containing daratumumab, bortezomib, lenalidomide and dexamethasone, was compared with VRd.
In the phase 3 CEPHEUS study, D-VRd (daratumumab/bortezomib/lenalidomide/dexamethasone) increased overall minimal residual disease (MRD)-negativity rates vs VRd in patients who were transplant ineligible/deferred with newly diagnosed multiple myeloma (NDMM).
PMID 42234958 · abstract-1
Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd.
PMID 42234958 · abstract-1
Supporting passages: The trial enrolled patients who were transplant-ineligible or deferred transplant as initial therapy, so it does not establish the same result for all newly diagnosed patients. Among patients who achieved minimal-residual-disease negativity, the progression-free-survival difference was not statistically significant, so an advantage in that subgroup remains uncertain. The median follow-up was 58.7 months, so outcomes beyond that period are not established.
Patients who were transplant-ineligible or deferred transplant as initial therapy were randomized to D-VRd or VRd.
PMID 42234958 · abstract-1
With 58.7-months median follow-up, overall MRD-negativity rates were significantly higher with D-VRd vs VRd (10-5: 60.9% vs 39.4%; odds ratio [OR], 2.37; 95% confidence interval [CI], 1.58-3.55; P< .0001; 10-6: 46.2% vs 27.3%; OR, 2.24; 95% CI, 1.48-3.40; P = .0001).
PMID 42234958 · abstract-1
Among patients who achieved MRD negativity, progression-free survival (PFS) trended in favor of D-VRd vs VRd (10-5: hazard ratio, 0.61; 95% CI, 0.35-1.06; P = .0755; 10-6: 0.66; 95% CI, 0.31-1.41; P = .2811).
PMID 42234958 · abstract-1
- Daratumumab in transplant-ineligible or -deferred newly diagnosed multiple myeloma: minimal residual disease in CEPHEUS. ↗
2026 Aug 25
Source checked: 2026-09-15