998PD - Management of infusion-related reactions (IRRs) in patients (pts) receiving daratumumab plus standard of care for the treatment of multiple myeloma...

Date 11 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Myeloproliferative Neoplasms
Haematologic Malignancies
Presenter Phillipe Moreau
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors P. Moreau1, N. Rabin2, T. Plesner3, K. Weisel4, P. Sonneveld5, M. Mateos6, J.M. Schecter7, H. Amin7, S. Trivedi8, M.A. Dimopoulos9
  • 1Hematology, University Hospital Hôtel-Dieu, 44000 - Nantes/FR
  • 2Department Of Haematology, University College London Hospitals NHS Trust, London/GB
  • 3Vejle Hospital, University of Southern Denmark, Vejle/DK
  • 4Universitaetsklinikum Tuebingen Der Eberhard-karls-universitaet, Abteilung fuer Innere Medizin II, Tuebingen/DE
  • 5Department Of Hematology, Erasmus MC, Rotterdam/NL
  • 6-, University of Salamanca Hospital, Salamanca/ES
  • 7-, Janssen Research & Development, LLC, Raritan/US
  • 8-, Janssen Research & Development, LLC, Spring House/US
  • 9Department Of Clinical Therapeutics, National And Kapodistrian University Of Athens, School Of Medicine, “Alexandra” General Hospital, Athens/GR

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Funding provided by Janssen Research & Development

Disclosure

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.