We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, EU Clinical Trials Register, ClinicalTrials.gov, WHO ICTRP, and conference proceedings from 2010 to September 2023.
SELECTION CRITERIA: We included four open-label, two-armed randomised controlled trials (34 publications) involving a total of 1783 participants. The ALCYONE, MAIA, and OCTANS trials were multicentre trials conducted worldwide in middle- and high-income countries. The AMaRC 03-16 trial was conducted in one high-income country, Australia. The mean age of participants was 69 to 74 years, and the proportion of female participants was between 40% and 54%. All trials evaluated
antineoplastic therapies with or without
daratumumab. In the ALCYONE and OCTANS trials,
daratumumab was combined with
bortezomib and
melphalan-
prednisone. In the AMaRC 03-16 study, it was combined with
bortezomib,
cyclophosphamide, and
dexamethasone, and in the MAIA study, it was combined with
lenalidomide and
dexamethasone. None of the included studies was blinded (high risk of performance and detection bias). One study was published as abstract only, therefore the risk of bias for most criteria was unclear. The other three studies were published as full texts. Apart from blinding, the risk of bias was low for these studies. Overall survival Treatment with
daratumumab probably increases overall survival when compared to the same treatment without
daratumumab (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.53 to 0.76, 2 studies, 1443 participants, moderate-certainty evidence). After a follow-up period of 36 months, 695 per 1000 participants survived in the control group, whereas 792 per 1000 participants survived in the
daratumumab group (95% CI 758 to 825). Progression-free survival Treatment with
daratumumab probably increases progression-free survival when compared to treatment without
daratumumab (HR 0.48, 95% CI 0.39 to 0.58, 3 studies, 1663 participants, moderate-certainty evidence). After a follow-up period of 24 months, progression-free survival was reached in 494 per 1000 participants in the control group versus 713 per 1000 participants in the
daratumumab group (95% CI 664 to 760). Quality of life Treatment with
daratumumab may result in a very small increase in quality of life after 12 months, evaluated on the EORTC QLQ-C30 global health status scale (GHS), when compared to treatment without
daratumumab (mean difference 2.19, 95% CI -0.13 to 4.51, 3 studies, 1096 participants, low-certainty evidence). The scale is from 0 to 100, with a higher value indicating a better quality of life. On-study mortality Treatment with
daratumumab probably decreases on-study mortality when compared to treatment without
daratumumab (risk ratio (RR) 0.72, 95% CI 0.62 to 0.83, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 366 per 1000 participants in the control group and 264 per 1000 participants in the
daratumumab group died (95% CI 227 to 304). Serious adverse events Treatment with
daratumumab probably increases serious adverse events when compared to treatment without
daratumumab (RR 1.18, 95% CI 1.02 to 1.37, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 505 per 1000 participants in the control group versus 596 per 1000 participants in the
daratumumab group experienced serious adverse events (95% CI 515 to 692). Adverse events (Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3) Treatment with
daratumumab probably results in little to no difference in adverse events (CTCAE grade ≥ 3) when compared to treatment without
daratumumab (RR 1.01, 95% CI 0.99 to 1.02, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 953 per 1000 participants in the control group versus 963 per 1000 participants in the
daratumumab group experienced adverse events (CTCAE grade ≥ 3) (95%
CI 943 to 972). Treatment with
daratumumab probably increases the risk of
infections (CTCAE grade ≥ 3) when compared to treatment without
daratumumab (RR 1.52, 95% CI 1.30 to 1.78, 3 studies, 1644 participants, moderate-certainty evidence). After the longest follow-up available (12 to 72 months), 224 per 1000 participants in the control group versus 340 per 1000 participants in the
daratumumab group experienced
infections (CTCAE grade ≥ 3) (95% CI 291 to 399).
AUTHORS' CONCLUSIONS: