Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities.
NEJM Evid
; 1(7): EVIDoa2200006, 2022 07.
Article
en En
| MEDLINE
| ID: mdl-38319255
ABSTRACT
BACKGROUND:
GLOW is a phase 3 trial evaluating the efficacy and safety of ibrutinib-venetoclax in older patients and/or those with comorbidities with previously untreated chronic lymphocytic leukemia (CLL).METHODS:
We randomly assigned (11) patients 65 years of age or older or those 18 to 64 years of age who also had a Cumulative Illness Rating Scale (CIRS) score greater than 6 (CIRS scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or creatinine clearance of less than 70 ml/min, to ibrutinib-venetoclax (3 cycles ibrutinib lead-in, then 12 cycles ibrutinib-venetoclax) or chlorambucil-obinutuzumab (6 cycles). The primary end point was progression-free survival (PFS) assessed by an independent review committee. Secondary end points included undetectable minimal residual disease (uMRD), response rates, and safety.RESULTS:
This study enrolled 211 patients, with 106 randomly assigned to ibrutinib-venetoclax and 105 to chlorambucil-obinutuzumab. With a median follow-up of 27.7 months, there were 22 PFS events for ibrutinib-venetoclax and 67 events for chlorambucil-obinutuzumab. PFS was significantly longer for ibrutinib-venetoclax than for chlorambucil-obinutuzumab (hazard ratio, 0.216; 95% confidence interval [CI], 0.131 to 0.357; P<0.001). The improvement in PFS with ibrutinib-venetoclax was consistent across predefined subgroups, including patients 65 years of age or older or with a CIRS score greater than 6. The best uMRD rate in bone marrow by next-generation sequencing was significantly higher for ibrutinib-venetoclax (55.7%) than for chlorambucil-obinutuzumab (21.0%; P<0.001). The proportion of patients with sustained uMRD in peripheral blood from 3 to 12 months after end of treatment was 84.5% for ibrutinib-venetoclax and 29.3% for chlorambucil-obinutuzumab. Four patients treated with ibrutinib-venetoclax required subsequent therapy compared with 27 patients receiving chlorambucil-obinutuzumab (hazard ratio, 0.143; 95% CI, 0.050 to 0.410). Adverse events grade 3 or greater occurred for 80 (75.5%) and 73 (69.5%) patients receiving ibrutinib-venetoclax and chlorambucil-obinutuzumab, respectively, with neutropenia being most common in both arms (37 [34.9%] and 52 [49.5%]). There were 11 (10.4%) and 12 (11.4%) all-cause deaths in the ibrutinib-venetoclax and chlorambucil-obinutuzumab arms, respectively.CONCLUSIONS:
Ibrutinib-venetoclax, an all-oral, once-daily, fixed-duration combination, demonstrated superior PFS and deeper and better sustained responses versus chlorambucil-obinutuzumab as first-line CLL treatment in older patients and/or those with comorbidities. (Funded by Janssen Research & Development, LLC, and Pharmacyclics; ClinicalTrials.gov number, NCT03462719.)
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperidinas
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Adenina
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Leucemia Linfocítica Crónica de Células B
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
NEJM Evid
Año:
2022
Tipo del documento:
Article