Daratumumab (D), a CD38-targeted monoclonal antibody, reduced the risk of MM progression or death by > 60% when combined with standard-of-care regimens in the phase 3 studies CASTOR (bortezomib [V] and dexamethasone [d] vs DVd; NCT02136134) and POLLUX (lenalidomide [R] and d vs DRd; NCT02076009). This analysis evaluated the management of D-related IRRs in the DVd and DRd arms of CASTOR and POLLUX.
Pts had MM and had received ≥1 line of therapy. In CASTOR, pts were given 8 21-day cycles of Vd (V 1.3 mg/m2 subcutaneously on Days 1, 4, 8, and 11; d 20 mg per os [PO]/intravenously [IV] on Days 1-2, 4-5, 8-9, and 11-12) ± D (16 mg/kg IV, weekly [QW] for Cycles 1-3, every 3 weeks [Q3W] for Cycles 4-8, then every 4 weeks [Q4W] thereafter). In POLLUX, pts were given 28-day cycles of Rd (R 25 mg PO on Days 1-21; d 40 mg QW) ± D (16 mg/kg IV QW for Cycles 1-2, every 2 weeks for Cycles 3-6, then Q4W thereafter). In addition, pre-infusion medication consisted of 20 mg d (or equivalent) IV/PO, 650-1000 mg paracetamol, and 25-50 mg diphenhydramine (or equivalent). Pts with high-risk respiratory complications received diphenhydramine on Days 1 and 2, a short-acting β2 adrenergic receptor agonist and control medications for lung disease after D infusion.
All pts receiving D were given pre-infusion medication. In CASTOR and POLLUX, 31 (13%) and 21 pts (7%) received post-infusion medications, respectively. In both trials, the median duration of D infusion was ∼7.0, 4.3, and ∼3.4 hours for the first, second, and subsequent infusions, respectively. IRRs occurred in 45% and 48% of pts and 98% and 96% of IRRs occurred during the first infusion in CASTOR and POLLUX, respectively. Most IRRs were grade 1/2 and no grade ≥4 IRRs were reported. The median time to onset of IRRs after starting the first D infusion was 84 minutes in CASTOR and 90 minutes in POLLUX. In CASTOR, 2 pts discontinued treatment due to IRRs; in POLLUX, 1 pt discontinued D due to a grade 3 IRR, but continued Rd.
Most D-related IRRs occurred during the first infusion and were grade 1/2. D-related IRRs were easily managed with pre- and post-infusion medications.
Clinical trial identification
NCT02136134 and NCT02076009
Legal entity responsible for the study
Janssen Research & Development, LLC
Funding provided by Janssen Research & Development
P. Moreau: Honoraria & Consultancy: Celgen, Takeda, Janssen, Novartis, Amgen. Speakers Bureau: Janssen, Celgene. N. Rabin: Consultancy: Janssen, Amgen, Novartis, Takeda, Bristol-Myers Squibb. Honoraria: Janssen, Takeda. Speakers Bureau: Janssen, Celgene. T. Plesner: Consultancy: Janssen, Takeda. Research Funding: Janssen. Advisory Committee: Janssen, Genmab. K. Weisel: Consultancy & Honoraria: Amgen, Bristol-Myers Squib, Celgene, Janssen, Novartis, Takeda, Onyx. Research Funding: Janssen, Celgene, Amgen, Sanofi. P. Sonneveld: Consultancy & Research Funding & Honoraria: Amgen, Celgene, Janssen, Karyopharm, Takeda. M-V. Mateos: Consultancy & Honoraria: Janssen, Celgene, Takeda, Amgen. J.M. Schecter: Employment & Equity: Janssen. H. Amin, S. Trivedi: Employment: Janssen. M.A. Dimopoulos: Consultancy & Honoraria: Celgene, Janssen, Takeda, Amgen.