In the open-label randomised phase 3 CANDOR trial, the addition of anti-CD38 antibody daratumumab to carfilzomib and dexamethasone reduced the risk of disease progression or death by 37% compared with carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma (MM).
Prof. Saad Z. Usmani (UNC-Chapel Hill School of Medicine, USA) presented the initial results of the trial, which randomised 466 patients (2:1 ratio) with relapsed/refractory MM previously treated with 1 to 3 prior therapies to either daratumumab + carfilzomib/dexamethasone (n=312) or carfilzomib/dexamethasone alone (n=154) . The primary endpoint of this study was progression-free survival (PFS). Key secondary endpoints were overall response rate, minimal residual disease-negative status, complete response rate at 12 months, overall survival (OS), duration of response, and safety.
The median PFS was not yet reached at median follow-up of 15.8 months, but the PFS was significantly improved with the addition of daratumumab versus carfilzomib/dexamethasone alone (HR 0.63; 95% CI 0.46-0.85; P=0.0014). The median OS had not yet been reached in either arm at a median follow-up of 17 months (HR 0.75; 95% CI 0.49-1.13; P=0.08). The overall response rate was 84.3% with daratumumab + carfilzomib/dexamethasone compared with 74.7% with only carfilzomib/dexamethasone (P=0.0040). Complete response was observed in 28.5% of the daratumumab + carfilzomib/dexamethasone arm versus 10.4% in the carfilzomib/dexamethasone arm. At 12 months, the minimal residual disease-negative rate was 12.5% for patients receiving daratumumab + carfilzomib/dexamethasone versus a mere 1.3% patients treated with carfilzomib/dexamethasone alone.
The safety profile was similar to what has been previously reported for each individual medicine. Grade ≥3 adverse events were reported in 56.2% (daratumumab + carfilzomib/dexamethasone¬) versus 45.8% patients (carfilzomib/dexamethasone). Treatment discontinuation rates due
to adverse events were similar in both arms (22.4% vs 24.8%, respectively). In the daratumumab + carfilzomib/dexamethasone arm, 5 treatment-related deaths occurred as compared with no deaths in the control arm; all were due to infections. Myeloma patients taking daratumumab are known to be at higher risk for infections attributable to reduced cellular immunity.
In conclusion, the CANDOR trial results showed deep and durable responses by adding daratumumab to carfilzomib/dexamethasone in relapsed/refractory MM patients, and the safety profile was consistent with previous experience.
1. Usmani SZ, et al. LBA-6, ASH 2019, 7-10 December, Orlando, USA.
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Table of Contents: ASH 2019
Letter from the Editor
Likely new standard of care: Blinatumomab for children with relapsed B-ALL
Pivotal phase 3 trial in cold agglutinin disease: sutimlimab can stop haemolysis
Oral azacitidine improves overall survival in patients with AML in remission
BCL11A as a novel target in gene therapy for sickle cell disease
Adding daratumumab to carfilzomib/dexamethasone prolongs PFS and OS in R/R MM
Long-term data of ropeginterferon alpha-2b in polycythaemia vera
Anti-CD70 is safe with hypomethylating agents in AML
MRD assessment to guide pre-emptive treatment decisions
Luspatercept effective for myelofibrosis-associated anaemia
Arsenic, ATRA, and ascorbic acid in acute promyelocytic leukaemia maintenance
Updated results ECOG-ACRIN E2906: decitabine maintenance after alloSCT
Sickle Cell Disease
Arginine supplements help against sickle cell disease pain
Abatacept prevents graft-versus-host disease in sickle cell patients after alloSCT
Plenary Scientific Session
HOVON-96: Better outcomes with cyclophosphamide after transplantation
Erythroferrone and skeletal changes associated with thalassaemia
Gene editing in congenital neutropenia
Experimental model for limitations of haematopoietic stem cells propagation
Mosunetuzumab: complete remissions in non-Hodgkin lymphoma
Socioeconomic disparities and survival in paediatric AML
Oral selinexor/pomalidomide/dexamethasone shows activity in heavily pre-treated multiple myeloma
CAR T-cell therapy successful in older non-Hodgkin’s lymphoma patients
Mild renal impairment in African Americans does not affect OS in AML
ALCYONE: New overall survival results for myeloma
Rivaroxaban is safe and effective for paediatric venous thromboembolism
Aspirin plus DOAC is not better than a DOAC alone
20-Year follow-up of imatinib in chronic myeloid leukaemia after failure with interferon
CAR T and Beyond
BCMA-targeted CAR T therapy yields 100% response in relapsed/refractory MM
Anti-BCMA/anti-CD38 in refractory multiple myeloma
Off-the-shelf natural killer cells