Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study.
Adult
Aged
Aged, 80 and over
Allografts
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Clinical Trials, Phase II as Topic
/ statistics & numerical data
Combined Modality Therapy
Diarrhea
/ chemically induced
Drug Administration Schedule
Female
Follow-Up Studies
Hematopoietic Stem Cell Transplantation
Humans
Hyperglycemia
/ chemically induced
Hypertension
/ chemically induced
Lymphoma, B-Cell
/ drug therapy
Male
Middle Aged
Multicenter Studies as Topic
/ statistics & numerical data
Neutropenia
/ chemically induced
Phosphoinositide-3 Kinase Inhibitors
/ adverse effects
Progression-Free Survival
Pyrimidines
/ adverse effects
Quinazolines
/ adverse effects
Salvage Therapy
/ adverse effects
Survival Analysis
Transplantation, Autologous
Treatment Outcome
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
06
12
2019
revised:
16
12
2019
accepted:
20
12
2019
pubmed:
24
12
2019
medline:
20
4
2021
entrez:
24
12
2019
Statut:
ppublish
Résumé
Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.
Substances chimiques
Phosphoinositide-3 Kinase Inhibitors
0
Pyrimidines
0
Quinazolines
0
copanlisib
WI6V529FZ9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
362-371Informations de copyright
© 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
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