Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas Journal Article
| Authors: | Soumerai, J. D.; Diefenbach, C. S.; Jagadeesh, D.; Asch, A.; Kumar, A.; Tsai, M. L.; Jandl, T. A.; Lossos, I. S.; Kenkre, V. P.; Awan, F.; Novotny, W.; Huang, J.; Miao, L.; Rajagopalan, P.; Ghalie, R. G.; Zelenetz, A. D. |
| Article Title: | Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas |
| 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. © 2024 British Society for Haematology and John Wiley & Sons Ltd. |
| Keywords: | adult; clinical article; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; overall survival; clinical trial; fatigue; mortality; neutropenia; diarrhea; drug efficacy; drug safety; drug withdrawal; antineoplastic agent; progression free survival; mantle cell lymphoma; anemia; nausea; thrombocytopenia; antineoplastic combined chemotherapy protocols; creatinine blood level; pyrimidines; aspartate aminotransferase blood level; hyperuricemia; maculopapular rash; b cell lymphoma; pyrazole derivative; multicenter study; pyrazoles; lymphoma; piperidines; phase 1 clinical trial; pyrimidine derivative; thiazoles; atrial fibrillation; follicular lymphoma; lymphoma, follicular; lymphoma, mantle-cell; piperidine derivative; eosinophilia; thiazole derivative; contusion; bruton tyrosine kinase; very elderly; humans; human; male; female; article; agammaglobulinaemia tyrosine kinase; ecog performance status; zanubrutinib; zandelisib; follicular cell lymphoma |
| Journal Title: | British Journal of Haematology |
| Volume: | 204 |
| Issue: | 5 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2024-05-01 |
| Start Page: | 1762 |
| End Page: | 1770 |
| Language: | English |
| DOI: | 10.1111/bjh.19419 |
| PUBMED: | 38500476 |
| PROVIDER: | scopus |
| PMCID: | PMC11156518 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
