Immune priming with avelumab and rituximab prior to R-CHOP in diffuse large B-cell lymphoma: the phase II AvR-CHOP study

Manos, K; Chong, G; Keane, C; Lee, ST; Smith, C; Churilov, L; McKendrick, J; Renwick, W; Blombery, P; Burgess, M; Nelson, NE; Fancourt, T; Hawking, J; Lin, W; Scott, AM; Barraclough, A; Wight, J; Grigg, A; Fong, CY; Hawkes, EA

Author(s): Manos, K; Chong, G; Keane, C; Lee, ST; Smith, C; Churilov, L; McKendrick, J; Renwick, W; Blombery, P; Burgess, M; Nelson, NE; Fancourt, T; Hawking, J; Lin, W; Scott, AM; Barraclough, A; Wight, J; Grigg, A; Fong, CY; Hawkes, EA;
Details: Publication Year 2023-05,Volume 37,Issue #5,Page 1092-1102
Journal Title: Leukemia
Publication Type: Research article
Abstract: Immune evasion, due to abnormal expression of programmed-death ligands 1 and 2 (PD-L1/PD-L2), predicts poor outcomes with chemoimmunotherapy in diffuse large B-cell lymphoma (DLBCL). Immune checkpoint inhibition (ICI) has limited efficacy at relapse but may sensitise relapsed lymphoma to subsequent chemotherapy. ICI delivery to immunologically intact patients may thus be the optimal use of this therapy. In the phase II AvR-CHOP study, 28 patients with treatment-naive stage II-IV DLBCL received sequential avelumab and rituximab priming ("AvRp;" avelumab 10 mg/kg and rituximab 375 mg/m2 2-weekly for 2 cycles), R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone for 6 cycles) and avelumab consolidation (10 mg/kg 2-weekly for 6 cycles). Grade 3/4 immune-related adverse events occurred in 11%, meeting the primary endpoint of a grade >/=3 irAE rate of <30%. R-CHOP delivery was not compromised but one patient ceased avelumab. Overall response rates (ORR) after AvRp and R-CHOP were 57% (18% CR) and 89% (all CR). High ORR to AvRp was observed in primary mediastinal B-cell lymphoma (67%; 4/6) and molecularly-defined EBV-positive DLBCL (100%; 3/3). Progression during AvRp was associated with chemorefractory disease. Two-year failure-free and overall survival were 82% and 89%. An immune priming strategy with AvRp, R-CHOP and avelumab consolidation shows acceptable toxicity with encouraging efficacy.
Publisher: Springer Nature
Keywords: Humans; Rituximab; Vincristine; *Neoplasm Recurrence, Local/drug therapy; *Lymphoma, Large B-Cell, Diffuse/pathology; Cyclophosphamide; Prednisone; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Treatment Outcome
Department(s): Clinical Haematology
PubMed ID: 36906715
Publisher's Version: https://doi.org/10.1038/s41375-023-01863-7
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-08-16 07:51:08

Last Modified: 2023-08-16 07:51:59