A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL

• Published in: Blood advances Vol. 7; no. 7; pp. 1137 - 1145
• Main Authors: Cherng, Hua-Jay J., Alig, Stefan K., Oki, Yasuhiro, Nastoupil, Loretta J., Fayad, Luis, Neelapu, Sattva S., Turturro, Francesco, Hagemeister, Fredrick, Craig, Alexander F. M., Macaulay, Charles W., Rodriguez, Maria Alma, Lee, Hun Ju, McDonnell, Timothy J., Flowers, Christopher R., Vega, Francisco, Green, Michael R., Feng, Lei, Kurtz, David M., Alizadeh, Ash A., Davis, R. Eric, Westin, Jason R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.04.2023; The American Society of Hematology
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cyclophosphamide - adverse effects; Doxorubicin - adverse effects; Humans; Lenalidomide - adverse effects; Lymphoid Neoplasia; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Prednisone - adverse effects; Rituximab - adverse effects; Vincristine - adverse effects
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022008174

•Lenalidomide, obintuzumab, and CHOP chemotherapy are efficacious and well tolerated treatments for newly diagnosed DLBCL.•LO-CHOP led to high molecular response rates based on circulating tumor DNA sequencing during and after treatment in this phase 1b/2 study. [Display omitted] Diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, one-third of patients experience refractory or relapsed disease. Studies comparing R-CHOP with modified regimens replacing R with obinutuzumab (O) or adding lenalidomide (L) did not result in improved outcomes; however, L and O together may enhance natural killer-cell mediated antibody-dependent cellular toxicity when paired with CHOP. Here, we report on a phase 1b/2 study of 53 patients with newly diagnosed DLBCL who received 6 cycles of LO-CHOP. The end of treatment overall and complete response rates of the 50 evaluable patients were 98% and 90%, respectively. After a median follow-up of 4.5 years, the 4-year progression free and overall survival rates were 87.4% and 91.3%, respectively. Grade 3 to 4 adverse events were experienced by 70% of patients, including neutropenia (38%), thrombocytopenia (17%), fatigue (13%), and neutropenic fever (13%). Of the 33 patients profiled with circulating tumor DNA (ctDNA) sequencing, 31 (94%) had detectable pretreatment ctDNA with cancer personalized profiling by deep sequencing, 24 (73%) were classifiable by the LymphGen classifier, and 15/20 (75%) and 12/17 (71%) patients achieved early and major molecular responses after 1 and 2 cycles, respectively. Using phased variant enrichment and detection sequencing, 16/18 evaluable patients (89%) showed no detectable ctDNA after at least 5 cycles of LO-CHOP. LO-CHOP demonstrates high efficacy and tolerability in newly diagnosed DLBCL, leading to a high rate of undetectable minimal residual disease by ctDNA. This trial has been registered at www.clinicaltrials.gov as NCT02529852.