997PD - Split dosing of daratumumab (D) in a phase 1b study of D plus carfilzomib (K)-based regimens in patients (pts) with multiple myeloma (MM)

Date 11 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Myeloproliferative Neoplasms
Haematologic Malignancies
Presenter Saad Usmani
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors S.Z. Usmani1, A. Jakubowiak2, A. Chari3, S. Lonial4, M. Mateos5, L. Benboubker6, K. Wu7, N.Z. Khokhar7, J. Wang8, P. Doshi7, P. Moreau9
  • 1Levine Cancer Institute, Carolinas HealthCare System, 28204 - Charlotte/US
  • 2-, University of Chicago Medical Center, Chicago/US
  • 3-, Icahn School of Medicine at Mount Sinai, New York/US
  • 4Department Of Hematology And Medical Oncology, Winship Cancer Institute, Emory University, Atlanta/US
  • 5-, University Hospital of Salamanca/IBSAL, Salamanca/ES
  • 6Service D’hématologie Et Thérapie Cellulaire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours/FR
  • 7-, Janssen Research & Development, LLC, Spring House/US
  • 8-, Janssen Research & Development, LLC, Raritan/US
  • 9Hematology, University Hospital Hôtel-Dieu, 44000 - Nantes/FR

Abstract

Background

D, a human CD38 IgGκ mAb, induces deep, durable responses in pts with relapsed/refractory MM, as monotherapy and combined with other regimens. Infusion-related reactions (IRRs) occur in ∼50% of D-treated pts, are generally mild to moderate, and usually occur during the 1st infusion. The median duration of the 1st infusion is ∼7 hours. To determine if splitting the first dose would reduce IRRs and infusion times, split-dose D was evaluated in two K-based regimens (MMY1001: NCT01998971).

Methods

Pts received D plus K and dexamethasone (d; DKd) or DKd and lenalidomide (R; DKRd). Pts in the DKd arm had 1-3 prior therapies; pts in the DKRd arm were newly diagnosed. 28-day cycles comprised K 20 mg/m2 intravenously (IV) over 30 minutes on Cycle 1 Day 1 (C1D1) and 70 mg/m2 over 30 minutes weekly, thereafter; and weekly d 40 mg (20 mg if > 75 years). In the DKRd arm, R 25 mg was given orally on Days 1-21. Pts received IV D as a single or split dose (Table). If C1D1 and C1D2 D infusions were not well-tolerated, C1D8 was given in 1000 mL. Pts received treatment until progression (DKd) or for ≤13 cycles (DKRd). To mitigate IRRs, d (20 mg) was given ≤3 hours before dosing on C1D1 and C1D2, and ≤3 hours before and the day after subsequent infusions. Paracetamol and diphenhydramine were given ≤3 hours before infusion. Montelukast was given prior to first D dose (optional thereafter).

Results

Thirty-two pts received split-dose D. Median age (range) was 61 (34-76) years. Median number of D cycles received was 12 (1-14). Median first infusion time was 4.2 (4.0-10.3) hours. Among pts who received split-dose D, 9 (28%) pts had an IRR. Five (16%) and 4 (13%) pts had grade 1 and grade 2 IRRs, respectively. No grade 3/4 IRRs occurred. IRRs reported in ≥ 2 pts were cough, throat irritation, nausea, and headache (2 pts [6%] each). Data will be updated.

Conclusions

A split first dose of D was associated with shorter infusion times and reduced incidence and lower grade of IRRs.Table:

997PD

Split dose C1D1 and C1D2 (8 mg/kg)Second dose C1D8 (16 mg/kg)Subsequent doses (16 mg/kg)
Initial rate, mL/hour5050100
Rate increment increase per hour, mL/hour505050
Maximum rate, mL/hour200200200
Total infusion, mL500500500

Clinical trial identification

NCT01998971

Legal entity responsible for the study

Janssen Research & Development, LLC

Funding

Funding provided by Janssen Research & Development

Disclosure

S.Z. Usmani: Research Funding: Onyx, Janssen, Sanofi, Array Biopharma, Pharmacyclics, Takeda, Celgene, Bristo-Myers Squibb. Speakers Bureau: Celgene, Amgen, Takeda. Advisory Board: Celgene, Skyline, Onyx, Millennium, Sanofi, Janssen. A. Jakubowiak: Consultancy & Advisory Committee: Janssen. A. Chari: Consultancy & Research Funding & Advisory Committee: Amgen, Array Biopharma, Celgene, Janssen, Millenium/Takeda, Novartis. S. Lonial: Advisory Committee: Millennium, Celgene, Novartis, Bristol-Myer Squib, Onyx, Janssen. Research Funding: Janssen. M-V. Mateos: Consultancy & Honoraria: Janssen, Celgene, Takeda, Amgen. L. Benboubker: Honoraria: Takeda, Celgene, Janssen, and Amgen. K. Wu, N.Z. Khokhar: Employment: Janssen. J. Wang: Employment & Stock Ownership: Janssen. P. Doshi: Employment & Royalties & Stock Ownership: Janssen. P. Moreau: Honoraria & Consultancy: Celgen, Takeda, Janssen, Novartis, Amgen. Speakers Bureau: Janssen, Celgene.