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).
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).
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.
A split first dose of D was associated with shorter infusion times and reduced incidence and lower grade of IRRs.Table:
|Split dose C1D1 and C1D2 (8 mg/kg)||Second dose C1D8 (16 mg/kg)||Subsequent doses (16 mg/kg)|
|Initial rate, mL/hour||50||50||100|
|Rate increment increase per hour, mL/hour||50||50||50|
|Maximum rate, mL/hour||200||200||200|
|Total infusion, mL||500||500||500|
Clinical trial identification
Legal entity responsible for the study
Janssen Research & Development, LLC
Funding provided by Janssen Research & Development
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.