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Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma
journal contributionposted on 21.12.2020, 00:32 by G Lenz, Eliza Hawkes, G Verhoef, C Haioun, S Thye Lim, D Seog Heo, K Ardeshna, G Chong, J Haaber, W Shi, I Gorbatchevsky, S Lippert, F Hiemeyer, P Piraino, G Beckmann, C Peña, V Buvaylo, BH Childs, G Salles
© 2020, The Author(s). Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in patients with relapsed/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO; activated B-cell like [ABC] and germinal center B-cell like [GCB]) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by CD79B mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, n = 19; GCB DLBCL, n = 30; unclassifiable, n = 3; missing, n = 15). The ORR was 19.4%; 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%/20.0% for patients with/without CD79B mutations (wild type, n = 45; mutant, n = 9; missing, n = 13). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including BCL2 (53.7%) and MLL2 (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.
This study was supported by research funding from Bayer AG. Bayer had a role in study design, data analysis, data interpretation, writing of the report, and decision to submit the paper for publication. Bayer had no role in data collection. The corresponding author (GL) had full access to all data and had final responsibility for the decision to submit for publication. Jack Adams, MSc, at Complete HealthVizion (Manchester, UK) provided medical writing assistance with this paper, based on detailed discussion and feedback from all the authors; this assistance was funded by Bayer AG. We thank Michael Pawlack and Oliver Wirtz for statistical programming in this study. Open access funding provided by Projekt DEAL.
Pagination14p. (p. 2184-2197)
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Science & TechnologyLife Sciences & BiomedicineOncologyHematologyCHEMOTHERAPY PLUS RITUXIMABPHOSPHOINOSITIDE 3-KINASETRANSPLANTATIONPATHOGENESISMECHANISMSCHOPHumansRecurrencePyrimidinesQuinazolinesMutationAdultAgedAged, 80 and overMiddle AgedFemaleMaleLymphoma, Large B-Cell, DiffuseHigh-Throughput Nucleotide SequencingCD79 AntigensPhosphoinositide-3 Kinase InhibitorsImmunology