A Randomized Study of Bortezomib, Cyclophosphamide and Dexamethasone Induction (VCD) Versus VCD and Daratumumab Induction Followed By Daratumumab Maintenance (VCDD) for the Initial Treatment of Transplant-Ineligible Patients with Multiple Myeloma (AMaRC 03-16)

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.4-5
• Main Authors: Mollee, Peter, Reynolds, John, Janowski, Wojt, Quach, Hang, Campbell, Philip, Gibbs, Simon D., Lee, Sophie, D'Rozario, James, Taylor, Kerry, Cochrane, Tara, Wallington-Beddoe, Craig Thomas, Kwok, Fiona, Weber, Nicholas, Kerridge, Ian H., Weston, Helen, Ho, Phoebe Joy, Horvath, Noemi, Yuen, Flora, Spencer, Andrew
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-138394

▪ Introduction Daratumumab, when added to standard of care regimens in relapsed and untreated myeloma, has consistently demonstrated significant improvements in response rates, induction of MRD negative responses and progression-free survival (PFS) while proving highly tolerable with minor increases in overall regimen toxicity. In non-transplant eligible patients daratumumab has been added in randomized studies to lenalidomide and dexamethasone (Rd) and bortezomib, melphalan and prednisolone (VMP) backbones, but not to the VCD regimen. Furthermore, the randomized studies excluded a significant proportion of patients with comorbidities so the benefit of daratumumab in a frail, elderly myeloma population remains untested. Methods Inclusion criteria included untreated patients with symptomatic myeloma who were considered ineligible for high-dose chemotherapy with autologous stem cell transplantation due to either age >65years or the presence of comorbidities. Any degree of renal impairment, including dialysis dependence, was allowed as were patients with a prior history of systemic malignancy that had been disease-free for 2 years. Patients were randomized 1:1 to receive VCD or VCDD. VCD consisted of nine 5-week cycles of V 1.3 mg/m2 SC on Days 1, 8, 15 and 22; C 300mg/m2 PO on Days 1, 8, 15 and 22 and D 20 mg PO on Days 1, 8, 15 and 22. VCDD consisted of nine 5-week cycles of VCD plus daratumumab 16 mg/kg IV on Days 1, 8, 15 and 22 of cycles 1 and 2, Days 1 and 15 of cycles 3 to 6 and Day 1 of cycles 7 to 9, followed by daratumumab maintenance 16 mg/kg IV every 4 weeks until progression. The primary endpoint was PFS with secondary endpoints being response rates, MRD, overall survival, toxicity and quality of life. Results A total of 129 patients were randomized, but 7 did not commence intended therapy. The following modified ITT analysis is based on the 122 randomized patients, 58 in the VCD group and 64 in the VCDD group, who received therapy. Baseline characteristics were balanced between the two arms. Median age was 76 years (range, 62-91yrs), with 19% being ≥80 years of age. 30% were female. ECOG performance status was 0 (34%),1 (26%), 2 (16%) and unknown (25%). ISS stage was I (16%), II (36%), III (23%) and unknown (24%). The estimated median potential follow-up is 12.6 months. At the time of this report, the COVID-19 pandemic had impacted collection of site data. As a result, the following outcome data is provisional with a full data set to be availabl