Abstract No: 8513
Background: Pts with RR MM received DARA for 9 wks in doses of 0.005-24mg/kg in the GEN501 dose-escalation part (Lokhorst: EHA 2013 abstract S576). The purpose of the GEN501 expansion part, which has completed enrollment, was to evaluate safety and efficacy of 2 doses of DARA for up to 24 mths using alternate dose schedules.
Methods: Pts ≥18 yrs, RR to at least 2 prior lines of therapy, incl. IMiDs and proteasome inhibitors, and ineligible for ASCT were enrolled at 2 dose levels: A: 8mg/kg +/- pre-dose (10mg) wkly for the first 8 infusions.B: 16mg/kg without pre-dose with a 3-wk washout period between the first 2 doses followed by 7 wkly doses. Then all pts were dosed every 2nd wk for 16 wks followed by dosing every 4th wk until disease progression, toxicity or for max 24 mths.
Results: Data from 30 pts in the 8mg/kg cohort and 15 pts in the 16mg/kg cohort recruited into the GEN501 expansion part are presented. Median age was 58.2 (35.1-76.9) and 64.1 (50.5-75.0) years, prior treatment lines were 5 (3-11), and 4 (2-8) and time since diagnosis was 5.5 (2.1-15.2) and 7.1 (0.4-13.3) years, respectively. Median number of DARA infusions was 10.5 vs 7.0, reflecting the more recent initiation of the 16mg/kg cohort. Infusion times were 3.5 vs 3.4 hours in the 8 and 16mg/kg groups, respectively. Safety: No dose-related increase in adverse events (AEs) was observed. Most common AEs reported (in ≥20% of all pts) were pyrexia, allergic rhinitis, fatigue, upper respiratory tract infection, diarrhea, dyspnea and cough. Only mild (Gr 1 and 2) infusion-related reactions (IRRs) were reported with 27% in the 16mg/kg group vs 20% in the 8mg/kg group. 2 SAEs, 1 in each group, were assessed as related to DARA (1 thrombocytopenia, 1 lymphocytopenia). One pt was withdrawn after 1st full dose due to thrombocytopenia Gr 3. Omission of the pre-dose increased neither the incidence nor the severity of IRRs.
Conclusions: DARA monotherapy in RR MM pts resulted in high single agent activity when administered at 16 mg/kg (46% ORR). The safety profile was manageable. Full response data will be presented at the meeting incl. bone marrow assessments.
Clinical trial information: NCT00574288.
Author(s): Henk M. Lokhorst, Jacob Laubach, Hareth Nahi, Torben Plesner, Peter Gimsing, Markus Hansson, Monique Minnema, Ulrik Niels Lassen, Jakub Krejcik, Tahamtan Ahmadi, Steen Lisby, Linda Basse, Nikolai C. Brun, Paul G. Richardson; UMC Utrecht, Utrecht, Netherlands; Harvard Medical School, Boston, MA; Karolinska Universitetssjukhuset-Huddinge, Huddinge, Sweden; Vejle Hospital, Vejle, Denmark; Copenhagen University Hospital, Copenhagen, Denmark; Skåne University Hospital, Lund, Sweden; Department of Oncology, Rigshospitalet, Copenhagen, Denmark; Janssen Research and Development, Spring House, PA; Genmab A/S, Copenhagen, Denmark; Dana-Farber Cancer Institute, Boston, MA