PS1425 RESULTS OF THE DARATUMUMAB MONOTHERAPY EARLY ACCESS TREATMENT PROTOCOL (EAP) IN PATIENTS FROM EUROPE AND RUSSIA WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA
Authors: Cook G. , Corso A. , Streetly M. , Mendeleeva L.P. , Ptushkin V.V. , Couturier C. , Chan E. , Iraqi W. , Al‐Akabawi A. , Pei H. , Gaudig M. , Petrucci M.T. , Alegre A. , Mateos M. Victoria 
Published: June 2019

Background:Daratumumab (DARA) is a human IgGκ monoclonal antibody targeting CD38 that is approved as monotherapy for relapsed or refractory MM (RRMM) and in combination with standard‐of‐care regimens for RRMM and transplant‐ineligible newly diagnosed MM. Despite the demonstrated benefit of DARA in patients with MM, not all patients are eligible for inclusion in clinical trials or have access to commercially available DARA.Aims:The purpose of this multicenter, open‐label, EAP was to provide early access to DARA monotherapy to eligible patients with RRMM, while collecting safety and patient‐reported outcomes (PRO) data. We report results from a pooled analysis of patients enrolled in 4 countries: Spain, Italy, Russia, and the United Kingdom.Methods:Patients eligible for study inclusion had to have ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or were double refractory to both a PI and IMiD. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression, unacceptable toxicity, study conclusion, or if DARA became available with reimbursement. Grade ≥3 treatment‐emergent adverse events (TEAEs), serious TEAEs (SAEs), infusion‐related reactions (IRRs), PRO, investigator‐assessed best response, and progression‐free survival (PFS) data were collected.Results:A total of 293 patients (median [range] age: 64 [32–85] years) were enrolled and received ≥1 dose of DARA. Baseline Eastern Cooperative Oncology Group score was 0, 1, and 2 for 38.2%, 50.5%, and 11.3% of patients, respectively. The median duration of treatment was 4.2 months (range: 0.03–24.08), with a median number of 13 infusions (range: 1–37). Median duration of infusions was 7.1, 4.3, and 3.5 hours for the first, second, and all subsequent infusions, respectively. Grade 3/4 TEAEs were reported in 176 (60.1%) patients; the most common (>10%) included thrombocytopenia (18.8%), anemia (11.9%), and neutropenia (11.6%). Common (>3%) SAEs included pneumonia (4.4%), pyrexia (4.1%), lower respiratory tract infection (3.8%), general physical health deterioration (3.8%), hypercalcemia (3.8%), and thrombocytopenia (3.4%). Primary reasons for treatment discontinuation included progressive disease (64.8%) and market authorization/reimbursement (16.7%), AE (11.3%), and death (2.7%). Sixty‐one (20.8%) patients discontinued treatment due to TEAEs (3.8% drug‐related). Forty (13.7%) patients had a fatal TEAE (none were drug‐related). IRRs occurred in 132 (45.1%) patients, including 10 (3.4%) with grade 3/4 IRRs (grade 3, n = 9 [3.1%]; grade 4, n = 1 [0.3%]). IRRs occurred in 44.4%, 1.8%, and 1.5% of patients during the first, second, and all subsequent infusions, respectively. The most common (>5%) any grade IRRs were dyspnea (8.9%), nasal congestion (8.9%), and cough (5.1%). A total of 97 (33.1%) patients achieved a partial response or better, with 36 (12.3%) patients achieving a very good partial response or better. Median PFS was 4.63 months (95% confidence interval [CI], 3.75–5.75), and the 12‐month PFS rate was 20.8% (95% CI, 15.9–26.2). The median change from baseline in all domains of the EQ‐5D‐5L, EORTC QLQ‐C30, and EORTC QLQ‐MY20 questionnaires was 0 or close to 0, which indicates no clinically significant changes.Summary/Conclusion:These EAP results are consistent with previously reported trials of daratumumab monotherapy, and confirm the safety of daratumumab in patients from Europe and Russia with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.