Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study

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Item Type:	Article
Title:	Safety and efficacy of glofitamab for relapsed/refractory large B-cell lymphoma in a multinational real-world study
Creators Name:	Shumilov, E., Wurm-Kuczera, R., Kerkhoff, A., Wang, M., Melchardt, T., Holtick, U., Bacher, U., Staber, P.B., Mazzeo, P., Leng, C., Böckle, D., Hölscher, A.S., Kauer, J., Rotter, N., Vucinic, V., Rudzki, J.D., Nachbaur, D., Bücklein, V.L., Schnetzke, U., Krämer, I., Wille, K., Hasse, A., von Tresckow, B., Hänel, M., Koenecke, C., Velazquez, G.F., Viardot, A., Schmid, C., Thurner, L., Wolf, D., Subklewe, M., Dreyling, M., Dreger, P., Dietrich, S., Keller, U., Jäger, U., Greil, R., Pabst, T., Lenz, G. and Chapuy, B.
Abstract:	Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) after at least two prior treatment lines, but real-world data is scarce. In this retrospective, multicenter, multinational study, we evaluated the outcomes of 70 patients with r/r DLBCL treated with glofitamab as part of the compassionate use patient program in the DACH region (Germany, Austria, Switzerland). The median number of prior treatment lines was four, with 71% of patients having received prior CAR-T therapy, and 71% being refractory to their last treatment. Cytokine release syndrome (CRS) was observed in 40% of patients (grade 3-4 in 2%), immune effector cell-associated neurotoxicity syndrome (ICANS) in 10% (grade 3 in 1%), and infections in 31% (grade 5 in 3%). The overall response rate was 47%, with 27% achieving complete responses (CR) and 20% partial responses (PR). The median progression-free survival (PFS) was 3.6 months, while the median overall survival (OS) was 5.7 months. Notably, 13 patients (19%) were in CR 6 months after initiation of glofitamab and exhibited durable responses. Elevated LDH is the most robust predictor of inferior outcome. Patients pretreated with bendamustine within 6 months prior glofitamab initiation exhibited significantly reduced PFS, suggesting that bendamustine may impair T-cell fitness and hence glofitamab efficacy. In summary, glofitamab demonstrates promising efficacy and a manageable safety profile in heavily pretreated r/r DLBCL patients in the real-world scenario and the optimal sequence of treatments should use T-cell-depleting agents before glofitamab with caution.
Source:	Blood Advances
ISSN:	2473-9529
Publisher:	American Society of Hematology
Page Range:	bloodadvances.2024014903
Date:	11 December 2024
Official Publication:	https://doi.org/10.1182/bloodadvances.2024014903
PubMed:	View item in PubMed

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