Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas.
Br J Haematol
; 204(5): 1762-1770, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38500476
ABSTRACT
The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazoles
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Pyrimidines
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Antineoplastic Combined Chemotherapy Protocols
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Lymphoma, Follicular
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Lymphoma, Mantle-Cell
Limits:
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
Language:
En
Journal:
Br J Haematol
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Br. j. haematol
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British journal of haematology
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: