Abstract
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.
Highlights
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, GermanyEastern Health Clinical School, Monash University, Olivia Newton John Cancer Research and Wellness Centre, Melbourne, VIC, AustraliaUniversity Hospitals Leuven, Leuven, Belgium 4 Lymphoid Malignancies Unit, Groupe Hospitalier Henri Mondor-Albert Chenevier, Creteil, France 5 National Cancer Centre Singapore and Duke-NUS MedicalSchool, Singapore, Singapore 6 Department of Internal Medicine, Seoul National UniversityMalignant lymphoma encompasses a heterogeneous group of malignancies [1]
1 2 Histology of tumor, n (%) Diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL) DLBCL not otherwise specified EBV-positive DLBCL of the elderly T-cell/histocyte-rich large B-cell lymphoma Stage at study entry, n (%) I II III IV Median time from initial diagnosis to start of study treatment, months Median time since first progression, months Median time from most recent progression to start of study treatment, months Median prior anticancer therapy lines, n Median time since last systemic anticancer therapy, months Refractory against last systemic anticancer therapy, n (%) Yes No
For patients with relapsed/refractory DLBCL, treatment options are still very limited, presenting an urgent need for novel therapeutic approaches. In this phase II study, monotherapy treatment with copanlisib demonstrated an objective response rate (ORR) of 19.4%, a response comparable with response rates reported with other nonchemotherapy single agents in unselected DLBCL, including the immunomodulatory agent lenalidomide (27.5%) [25] and the Bruton’s tyrosine kinase inhibitor ibrutinib (25%) [26]
Summary
Eastern Health Clinical School, Monash University, Olivia Newton John Cancer Research and Wellness Centre, Melbourne, VIC, Australia. Diffuse large B-cell lymphoma (DLBCL), characterized by aggressive clinical behavior, is Hospital, Seoul, South Korea 7 University College London Hospitals NHS Foundation Trust, London, UK 8 Ballarat Regional Integrated Cancer Centre, Ballarat, VIC, Australia 9 Department of Hematology, Odense University Hospital, Odense, Denmark Bayer China, Beijing, China Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA Pharmaceuticals Division, Bayer AG, Berlin, Germany Hospices Civils de Lyon, Université de Lyon, Centre Hospitalier. Patients with relapsed/refractory DLBCL are characterized by adverse prognosis [6, 7]. High-dose chemotherapy followed by autologous stem cell transplantation remains the current standard of care for patients with relapsed/refractory DLBCL, longterm outcomes are poor [7]. Novel therapies are urgently required to improve outcomes for DLBCL patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
