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- Title
Corticosteroid Tapering in Patients with Relapsed or Refractory Multiple Myeloma Receiving Subcutaneous Daratumumab: Part 3 of the Open-Label, Multicenter, Phase 1b PAVO Study.
- Authors
Kaufman, Jonathan L.
- Abstract
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 treatmentemergent 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.
- Subjects
MULTIPLE myeloma; PAVO; RESPIRATORY infections; CORTICOSTEROIDS; LYMPHOPENIA
- Publication
Journal of Hematology Oncology Pharmacy, 2021, Vol 11, p8
- ISSN
2164-1153
- Publication type
Article