Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma

• Published in: Blood advances Vol. 7; no. 8; pp. 1488 - 1495
• Main Authors: Younes, Anas, Burke, John M., Cheson, Bruce D., Diefenbach, Catherine S., Ferrari, Silvia, Hahn, Uwe H., Hawkes, Eliza A., Khan, Cyrus, Lossos, Izidore S., Musuraca, Gerardo, Tani, Monica, Vitolo, Umberto, Yuen, Sam, Raval, Aparna, Shivhare, Mahesh, Nielsen, Tina G., Sellam, Gila, Sharman, Jeff P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2023; The American Society of Hematology
• Subjects: Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Clinical Trials and Observations; Cyclophosphamide - adverse effects; Doxorubicin - adverse effects; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone - adverse effects; Rituximab - adverse effects; Vincristine - adverse effects
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022008344

•Atezo–R-CHOP appeared to improve CR rates compared with historical controls but not so much as to warrant further study.•The atezo–R-CHOP combination introduced immune-related AEs; however, these did not interfere with the delivery of R-CHOP. [Display omitted] Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) and is curative in ∼60% of patients. Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets programmed death–ligand 1 and has previously shown antitumor activity in several tumor types. In a phase 1b/2 trial (NCT02596971), we evaluated the safety and efficacy of atezolizumab in combination with R-CHOP (atezo–R-CHOP; for 6-8 cycles) in patients with previously untreated DLBCL. Patients achieving a complete response (CR) at the end of induction received consolidation therapy with atezolizumab on day 1 of each 21-day cycle for an additional 17 cycles. Overall, 42 patients with DLBCL were included in this analysis. The primary endpoint, CR rate at the end of induction, as assessed by an independent review committee (modified Lugano 2014 criteria), was 77.5% (95% confidence interval [CI], 64.0-87.7; n = 40). Investigator-assessed progression-free survival and overall survival at 3 years were 77.4% (95% CI, 59.7-88.0) and 87.2% (95% CI, 71.9-94.5), respectively. All treated patients experienced ≥1 adverse event (AE; 32 patients [76.2%] had grade 3-4 AE). One patient had a fatal AE (unconfirmed progressive multifocal leukoencephalopathy) that was considered related to atezolizumab and rituximab, and 17 patients (40.5%) experienced atezolizumab-related AEs of special interest. In previously untreated patients with DLBCL, atezo–R-CHOP demonstrated encouraging clinical efficacy and a safety profile consistent with the known toxicities of the individual drugs. This trial was registered at www.clinicaltrials.gov as #NCT02596971.