Presenter: Jonathan L. Kaufman, MD, Associate Professor and Associate Vice-Chair, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
Co-Authors: Hareth Nahi, Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden; Saad Z. Usmani, Levine Cancer Institute/Atrium Health, Charlotte, NC; Maria-Victoria Mateos, University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain; Niels W.C.J. van de Donk, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, The Netherlands; Philippe Moreau, Hematology, University Hospital Hôtel-Dieu, Nantes, France; Albert Oriol, Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain; Torben Plesner, Vejle Hospital and University of Southern Denmark, Vejle, Denmark; Shiyi Yang, Janssen Research & Development, Spring House, PA; Peter Hellemans, Janssen Research & Development, Beerse, Belgium; Brenda Tromp, Janssen Research & Development, Leiden, The Netherlands; Man (Melody) Luo, Janssen Research & Development, Raritan, NJ; Donna Zemlickis, Janssen Research & Development, Toronto, Ontario, Canada; Andrew Farnsworth, Janssen Research & Development, High Wycombe, United Kingdom; Ajai Chari, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY
Background: Intravenous (IV) daratumumab is approved for the treatment of multiple myeloma. In the PAVO study Part 2, subcutaneous (SC) daratumumab, a coformulation of daratumumab and recombinant human hyaluronidase PH20 (rHuPH20), was well-tolerated, showed low infusion-related reaction (IRR) rates, consistent serum concentrations, and similar efficacy to IV daratumumab in relapsed or refractory multiple myeloma. This study represents Part 3 of the PAVO study.
Objective: To evaluate the safety of pre- and postdose corticosteroid tapering during SC daratumumab administration.
Methods: Relapsed or refractory multiple myeloma patients with ≥2 previous treatment lines received SC daratumumab (daratumumab 1800 mg plus rHuPH20 30,000 U in 15 mL) by manual SC injection per approved IV monotherapy dosing schedule. Patients received a 3-week tapering schedule (corticosteroid-free by cycle 1, day 22), with methylprednisolone given orally or intravenously predose (cycle 1, day 1, 100 mg; cycle 1, day 8, 60 mg; cycle 1, day 15, 30 mg) and orally postdose (cycle 1, day 1, 20 mg for 2 days; cycle 1, day 8, 20 mg for 1 day; cycle 1, day 15, 20 mg for 1 day), or a 2-week tapering schedule (corticosteroid-free by cycle 1, day 15), with methylprednisolone given orally or intravenously predose (cycle 1, day 1, 100 mg; cycle 1, day 8, 60 mg) and orally postdose (cycle 1, day 1, 20 mg for 2 days; cycle 1, day 8, 20 mg for 1 day).
Results: A total of 15 patients in each group received a median of 2 previous lines of therapy (range, 2-7), with 37% of patients having disease refractory to a proteasome inhibitor and an immunomodulatory drug. The 3-week and 2-week groups received a median of 14 (range, 2-22) and 12 (range, 3-19) SC daratumumab doses without corticosteroids, respectively. No IRRs were reported in the 3-week group. Three (20%) patients in the 2-week group had IRRs on cycle 1, day 1 (including grade 3 hypertension, grade 2 chills, grade 1 pyrexia, grade 1 oropharyngeal pain, and grade 1 tachycardia). IRRs occurred within 2 hours of the first administration; no IRRs were reported at later administrations. Most common (≥25%) treatment-emergent adverse events (AEs) in the 3-week and 2-week groups were upper respiratory tract infection (53% and 40%, respectively), nausea (47% and 20%, respectively), and fatigue (27% in each group). Most common (≥5%) grade 3 or 4 treatment-emergent AEs were neutropenia (0% and 20%, respectively), lymphopenia and hypertension (13% each and 0% each, respectively), and anemia (7% each). At a median follow-up of 7.7 months (in the 3-week group) and 5.6 months (in the 2-week group), the overall response rates were 40% each, and very good or better partial response rates were 13% and 27%, respectively.
Conclusion: Rapid corticosteroid tapering over 3 or 2 weeks is safe in patients with relapsed or refractory multiple myeloma receiving SC daratumumab. These data help guide future SC daratumumab combinations (ie, T-cell redirectors, CAR T-cell, or checkpoint inhibitors), where limiting concurrent corticosteroids may be preferred.