A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
| Autor: | Ravi Vij, Claire Brillac, Jesús F. San-Miguel, Marielle Chiron, Corina Oprea, Parameswaran Hari, Nikoletta Lendvai, Jeffrey A. Zonder, Cristina Gasparetto, Thomas Martin, Joshua R. Richter, Meletios A. Dimopoulos, Joseph R. Mikhael, Eric Charpentier, William I. Bensinger, Enrique M. Ocio, Shaji Kumar, Craig E. Cole, Jonathan L. Kaufman |
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| Přispěvatelé: | Universidad de Cantabria |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Nausea Phases of clinical research Myeloma Cancer immunotherapy Proteasome inhibitors Relapsed/refractory multiple myeloma Antibodies Monoclonal Humanized Gastroenterology Article Refractory Internal medicine Isatuximab (anti-CD38 mAb) medicine Humans Progression-free survival Adverse effect Multiple myeloma Aged Isatuximab Aged 80 and over business.industry Phase 2 study Hematology Middle Aged medicine.disease ADP-ribosyl Cyclase 1 Progression-Free Survival Oncology Monoclonal Female medicine.symptom Neoplasm Recurrence Local business Multiple Myeloma Multiple myeloma gammopathies |
| Zdroj: | Leukemia . 2020 Dec;34(12):3298-3309 Leukemia UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) |
| Popis: | A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38–85), 5 (2–14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ≥10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ≤2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ≤2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ≥10 mg/kg. |
| Databáze: | OpenAIRE |
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