Cargando…
A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
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/k...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685976/ https://www.ncbi.nlm.nih.gov/pubmed/32409691 http://dx.doi.org/10.1038/s41375-020-0857-2 |
_version_ | 1783613272662999040 |
---|---|
author | Mikhael, Joseph Richter, Joshua Vij, Ravi Cole, Craig Zonder, Jeffrey Kaufman, Jonathan L. Bensinger, William Dimopoulos, Meletios Lendvai, Nikoletta Hari, Parameswaran Ocio, Enrique M. Gasparetto, Cristina Kumar, Shaji Oprea, Corina Chiron, Marielle Brillac, Claire Charpentier, Eric San-Miguel, Jesús Martin, Thomas |
author_facet | Mikhael, Joseph Richter, Joshua Vij, Ravi Cole, Craig Zonder, Jeffrey Kaufman, Jonathan L. Bensinger, William Dimopoulos, Meletios Lendvai, Nikoletta Hari, Parameswaran Ocio, Enrique M. Gasparetto, Cristina Kumar, Shaji Oprea, Corina Chiron, Marielle Brillac, Claire Charpentier, Eric San-Miguel, Jesús Martin, Thomas |
author_sort | Mikhael, Joseph |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7685976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76859762020-12-03 A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma Mikhael, Joseph Richter, Joshua Vij, Ravi Cole, Craig Zonder, Jeffrey Kaufman, Jonathan L. Bensinger, William Dimopoulos, Meletios Lendvai, Nikoletta Hari, Parameswaran Ocio, Enrique M. Gasparetto, Cristina Kumar, Shaji Oprea, Corina Chiron, Marielle Brillac, Claire Charpentier, Eric San-Miguel, Jesús Martin, Thomas Leukemia Article 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. Nature Publishing Group UK 2020-05-14 2020 /pmc/articles/PMC7685976/ /pubmed/32409691 http://dx.doi.org/10.1038/s41375-020-0857-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mikhael, Joseph Richter, Joshua Vij, Ravi Cole, Craig Zonder, Jeffrey Kaufman, Jonathan L. Bensinger, William Dimopoulos, Meletios Lendvai, Nikoletta Hari, Parameswaran Ocio, Enrique M. Gasparetto, Cristina Kumar, Shaji Oprea, Corina Chiron, Marielle Brillac, Claire Charpentier, Eric San-Miguel, Jesús Martin, Thomas A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma |
title | A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma |
title_full | A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma |
title_fullStr | A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma |
title_full_unstemmed | A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma |
title_short | A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma |
title_sort | dose-finding phase 2 study of single agent isatuximab (anti-cd38 mab) in relapsed/refractory multiple myeloma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685976/ https://www.ncbi.nlm.nih.gov/pubmed/32409691 http://dx.doi.org/10.1038/s41375-020-0857-2 |
work_keys_str_mv | AT mikhaeljoseph adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT richterjoshua adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT vijravi adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT colecraig adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT zonderjeffrey adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT kaufmanjonathanl adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT bensingerwilliam adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT dimopoulosmeletios adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT lendvainikoletta adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT hariparameswaran adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT ocioenriquem adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT gasparettocristina adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT kumarshaji adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT opreacorina adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT chironmarielle adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT brillacclaire adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT charpentiereric adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT sanmigueljesus adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT martinthomas adosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT mikhaeljoseph dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT richterjoshua dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT vijravi dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT colecraig dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT zonderjeffrey dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT kaufmanjonathanl dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT bensingerwilliam dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT dimopoulosmeletios dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT lendvainikoletta dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT hariparameswaran dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT ocioenriquem dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT gasparettocristina dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT kumarshaji dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT opreacorina dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT chironmarielle dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT brillacclaire dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT charpentiereric dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT sanmigueljesus dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma AT martinthomas dosefindingphase2studyofsingleagentisatuximabanticd38mabinrelapsedrefractorymultiplemyeloma |