The addition of the novel BTK inhibitor, orelabrutinib, with rituximab, cyclophosphamide, doxorubicin, and vincristine (RCHOP) resulted in a high response rate with a tolerable safety profile among patients with extranodal, non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL), according to the results of a study presented at the ESMO Congress 2022.

Patients with extranodal invasion of DLBCL have a particularly poor prognosis and represent an unmet clinical need. Prior studies suggested that BTK inhibitors may have activity against non-GCB DLBCL. The aim of this trial was to evaluate the efficacy and safety of orelabrutinib.

The trial treated 22 patients with non-GCB DLBCL and confirmed extranodal disease to receive orelabrutinib plus RCHOP on a 21-day cycle for 6 cycles. The primary endpoint was overall response rate (ORR) and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. The median follow-up was 11 months.

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At baseline, the median age was 52 and 36.3% of patients were male. The majority of patients had stage IV disease and 50% had an International Prognostic Index of 3 to 5. There were 54.5% of patients who had MYC/BCL2 double-expressing disease and 13.6% had a TP53 mutation. The most common extranodal sites of invasion were the pericardium, pleura, or peritoneum, gastrointestinal tract, and kidney or adrenal gland.

The addition of orelabrutinib to RCHOP resulted in an ORR of 86.4%, including 77.3% of patients who achieved a complete response (CR). Patients with double-expressor or non-double-expressor DLBCL demonstrated a CR rate of 75% and 80%, respectively.

The median PFS was not evaluable and the 5-month rate was 90.9%. Serious adverse events included febrile neutropenia among 13.6% of patients, pneumonia among 9.1%, and atrial flutter among 4.5%.

The authors concluded that “the efficacy of orelabrutinib plus RCHOP for non-GCB DLBCL with extranodal disease is impressive in this single-center clinical practice and the toxicity is acceptable.”


Wang M, Ke Q, Li Z, et al. Orelabrutinib plus RCHOP for previously untreated non-germinal center b cell-like (GCB) diffuse large b cell lymphoma (DLBCL) patients with extranodal disease. Presented at ESMO 2022; September 9-13, 2022. Abstract 627MO.