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

Kate Manos, Geoffrey Chong, Colm Keane, Sze Ting Lee, Charmaine Smith, Leonid Churilov, Joseph McKendrick, William Renwick, Piers Blombery, Melinda Burgess, Niles Elizabeth Nelson, Tineke Fancourt, Joanne Hawking, Wendi Lin, Andrew M. Scott, Allison Barraclough, Joel Wight, Andrew Grigg, Chun Yew Fong, Eliza A. Hawkes

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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.

Original languageEnglish
Pages (from-to)1092–1102
Number of pages11
JournalLeukemia
Volume37
DOIs
Publication statusPublished - May 2023
Externally publishedYes

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