The CASTOR studyr investigated the role of daratumumab when added to bortezomib and dexamethasone. In this randomised, Phase III open-label study, patients who had received at least one prior line of therapy were assigned to receive up to 8 cycles of subcutaneous bortezomib, given days 1,4,8 and 11 of a 21 day cycle, in combination with dexamethasone given on the day of, and day after, each bortezomib administration. Patients randomised to the experimental arm additionally received daratumumab once-weekly for the first 3 cycles, followed by 3-weekly doses (given on day 1 of each cycle) for cycles 4-8, followed by 4-weekly doses until progressive disease or discontinuation due to toxicity. Patients may have received prior bortezomib if they were not refractory to it and had not discontinued due to toxicity. The primary end-point was progression-free survival (PFS). Show Efficacy251 patients were randomised to receive daratumumab; 247 were assigned to the control group. After a median follow-up of 7.4 months, the median progression-free survival (PFS) was not reached (NR) in the daratumumab arm, and 7.2 months in the control group (HR 0.39, p<0.001). The 12 month PFS was 60.7% versus 26.9%, favouring the daratumumab arm. Overall response rate was 82.9% in the daratumumab group versus 63.2% in the control group (p<0.001). Similarly, complete response rates favoured the experimental arm (19.2% v 9.0%, p=0.001).  © NEJM 2016 © NEJM 2016 An update of CASTOR with three years of follow-up has been publishedr, and a more recent abstract presentation confirmed ongoing efficacy at 4 years of follow-up.r With a median follow-up of 47 months, PFS remained significantly prolonged in the daratumumab arm compared to the control arm (median 16.7 vs 7.1 months, P <0.00001). 3-year overall survival was similar at 61% and 51% respectively. A recent sub-analysis explored the effect of cytogenetic risk on outcomes in the CASTOR data.r In this analysis at median of 40 months follow-up, DVd prolonged PFS compared with Vd in both standard (16.6 vs 6.6 months, p<0.0001) and high (12.6 vs 6.2 months, p=0.0106) cytogenetic risk. Higher rates of MRD negativity and sustained MRD negativity were seen in the DVd group regardless of cytogenetic risk. The use of once-weekly bortezomib in combination with daratumumab and dexamethasone has not been investigated in prospective studies. Small retrospective studies demonstrate efficacy and tolerability, particularly in patients with pre-existing neuropathy.r ToxicityOverall rates of adverse events were similar in the two groups. Grades 3 and 4 events were more common in the daratumumab arm (76.1% v 62.4%), with haematological toxicity (thrombocytopenia, anaemia and neutropenia) being the most common adverse events with higher incidence rates. Rates of discontinuation were similar in the two groups. Infusion-related reactions were common, but almost all were Grades 1 and 2.r No new safety signals were identified in the 4-year follow-up data, although noting the incidence of second primary malignancy was 4.9% in the daratumumab arm and 1.7% in the Vd arm.r © NEJM 2016
Under a Creative Commons license Open access AbstractBackgroundIn the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed. Patients and MethodsEligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m2) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression. ResultsOf 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10−5) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed. ConclusionAfter 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates. KeywordsClinical trial Efficacy Minimal residual disease Relapsed/refractory Safety Cited by (0)© 2019 Janssen Global Services, LLC. Published by Elsevier Inc. How long does it take daratumumab to work?Treatment durations of up to 25 months have been reported in clinical trials (range 0.1 month to 40.44 months). Research suggests people with IgG MM may be more responsive to Darzalex treatment. In clinical trials, it took approximately one month for Darzalex to start working.
Is daratumumab an immunotherapy or chemo?Darzalex contains daratumumab. This is a type of drug called a monoclonal antibody. Darzalex isn't chemotherapy. It's a type of biologic treatment and is sometimes called targeted therapy or immunotherapy.
What is the success rate of daratumumab?Daratumumab, Lenalidomide, and Dexamethasone
The overall response rate was 81%, with 34% of patients achieving a complete response or better and 63% achieving a very good partial response (VGPR) or better.
What is first line treatment for multiple myeloma?The combination of a proteasome inhibitor and an immunomodulatory agent plus the steroid dexamethasone is the standard of care for newly diagnosed patients.
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Daratumumab bortezomib and dexamethasone for multiple myeloma
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