A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma.
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bridged Bicyclo Compounds, Heterocyclic
/ administration & dosage
Cyclophosphamide
/ administration & dosage
Doxorubicin
/ administration & dosage
Fatigue
/ chemically induced
Female
Gastrointestinal Diseases
/ chemically induced
Genes, bcl-2
Granulocyte Colony-Stimulating Factor
/ therapeutic use
Hematologic Diseases
/ chemically induced
Humans
Infections
/ etiology
Kaplan-Meier Estimate
Lymphoma, Large B-Cell, Diffuse
/ drug therapy
Male
Middle Aged
Neoplasm Proteins
/ antagonists & inhibitors
Prednisone
/ administration & dosage
Proto-Oncogene Proteins c-bcl-2
/ antagonists & inhibitors
Rituximab
/ administration & dosage
Sulfonamides
/ administration & dosage
Vincristine
/ administration & dosage
Young Adult
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
04 02 2021
04 02 2021
Historique:
received:
22
04
2020
accepted:
24
08
2020
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
22
5
2021
Statut:
ppublish
Résumé
The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and research_plete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups.
Identifiants
pubmed: 33538797
pii: S0006-4971(21)00205-6
doi: 10.1182/blood.2020006578
pmc: PMC7869186
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
Neoplasm Proteins
0
Proto-Oncogene Proteins c-bcl-2
0
Sulfonamides
0
Granulocyte Colony-Stimulating Factor
143011-72-7
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
venetoclax
N54AIC43PW
Prednisone
VB0R961HZT
Banques de données
ClinicalTrials.gov
['NCT02055820']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
600-609Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2021 by The American Society of Hematology.
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