Daratumumab: a game changer in myeloma therapy

Saad Usmani and colleagues 1 Usmani SZ Nahi H Plesner T et al. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020; 7: e447-e455 Summary Full Text Full Text PDF Scopus (20) Google Scholar present the long term follow-up of pooled data from two phase 2 studies (GEN-501 and SIRIUS) including 148 heavily pretreated patients given daratumumab monotherapy for relapsed and refractory multiple myeloma. Usmani and colleagues report that the proportion of patients with overall response rate was 30·4% (95% CI 23·1–38·5%) with a median progression-free survival of 4·0 months (2·8–5·6, unchanged from earlier analysis) and median overall survival of 20·5 months (16·6–28·1). These findings are in line with a report from the Intergroup Francophone du Myelome 2 Boyle EM Leleu X Petillon MO et al. Daratumumab and dexamethasone is safe and effective for triple refractory myeloma patients: final results of the IFM 2014-04 (Etoile du Nord) trial. Br J Haematol. 2019; 187: 319-327 Crossref PubMed Scopus (10) Google Scholar using daratumumab and dexamethasone in patients with relapsed and refractory multiple myeloma, wherein an overall response rate of 33% was observed, with median progression-free survival of 6·6 months in responding patients (95% CI 3·7–14·0), and overall survival of 16·5 months in responding patients (11·2–24·0). Usmani and colleagues report more favourable results than real-world data from 41 patients, 3 Jullien M Trudel S Tessoulin B et al. Single-agent daratumumab in very advanced relapsed and refractory multiple myeloma patients: a real-life single-center retrospective study. Ann Hematol. 2019; 98: 1435-1440 Crossref PubMed Scopus (17) Google Scholar that showed an overall response rate of 24%, median progression-free survival of 1·5 months, and overall survival of 6·5 months. Likewise, the ORR in patients treated with daratumumab was 23% in a large early access programme in the USA. 4 Chari A Lonial S Mark TM et al. Results of an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma. Cancer. 2018; 124: 4342-4349 Crossref PubMed Scopus (14) Google Scholar These differences in treatment outcome highlight the effect of patient characteristics. Although 128 (86%) of 148 patients in the analysis presented by Usmani and colleagues 1 Usmani SZ Nahi H Plesner T et al. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020; 7: e447-e455 Summary Full Text Full Text PDF Scopus (20) Google Scholar were double refractory, and had a median of 5 (IQR 4–7) previous lines of therapy, the median time from diagnosis to enrolment was 5·1 years (3·9–7·8), indicating that many of the relatively young patients with a median age of 64 years (58–70) had a more favourable prognosis. This notion is further supported by the partial or better response reported in 44 (37%) of 119 patients who received rescue therapy after discontinuation of daratumumab. Cytogenetic data were not available, but other studies 5 Nooka AK Kaufman JL Hofmeister CC et al. Daratumumab in multiple myeloma. Cancer. 2019; 125: 2364-2382 Crossref PubMed Scopus (45) Google Scholar report that daratumumab usually does not overcome the negative effect of high-risk cytogenetics. If patients were treated according to the US Food and Drug Administration recommendations for reduction of infusion-related reactions, the so-called daratumumab monotherapy is in fact a doublet, including corticosteroids in doses equivalent to about 30 mg dexamethasone per infusion. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trialsIn this analysis, daratumumab 16 mg/kg monotherapy showed durable responses and there were no new safety concerns with longer follow-up. Full-Text PDF