819P - Efficacy and safety of orelabrutinib plus R-CHOP-like regimens for treatment-naïve diffuse large B-cell lymphoma with double expression

Background

Orelabrutinib (O) is a novel and potent BTK inhibitor with higher selectivity and fewer off-target than other BTK inhibitors. Besides, O hardly inhibits ITK kinase activity and therefore preserves NK-cell-mediated ADCC induced by rituximab and thus boosts the apoptosis of tumor cells. This observational study evaluated the efficacy and safety of O plus R-CHOP-like regimens for treatment-naïve pts with double expression (DE) DLBCL.

Methods

Eligible pts received R-CHOP-like regimens on a 21-day cycle plus O (150 mg/day). Tumor assessments were performed at the end of cycles 2 and 4 and at the end of treatment. After 4 cycles of treatment, pts were evaluated for eligibility of ASCT. Fit pts underwent mobilization and collection of stem cells at cycle 5, and the treatment was completed with continuation of O plus R-CHOP-like regimens in cycle 6, followed by ASCT. Pts not eligible for ASCT continued to receive 2 or 4 cycles of O plus R-CHOP-like regimens. The primary endpoint was complete response rate (CRR) at the end of treatment. Secondary endpoints included PFS, OS, and safety.

Results

As of data cut-off on April 20, 2024, 20 pts were enrolled. The median age of the 20 pts was 58.0 (range, 29.0-81.0) years. Majority of pts were female (12/20, 60.0%), had stage IV disease (16/20, 80.0%), had elevated lactate dehydrogenase level (14/20, 70.0%), and had an IPI score of 2-5 (16/20, 80.0%). Seven (35%) pts presented with central high risk. Of the 20 pts, 16 had completed the treatment and the remaining 4 had completed > 4 cycles of treatment. The CRR was 65.0% (13/20) at the end of cycle 2, 85.0% (17/20) at the end of cycle 4, and 93.8% (15/16) at the end of treatment. After a median follow-up of 13.0 (range, 3.0-39.0) months, the 1-year PFS and OS rates were 93.3% and 100.0%, respectively. Grade 3-4 adverse events were reported in 40.0% of pts, with neutropenia (35%) and interstitial pneumonia (5%) commonly reported. No death, cardiotoxicity, or bleeding occurred.

Conclusions

The first-line combination regimen of O plus R-CHOP-like regimens was effective and well-tolerated in pts with DE DLBCL. The study is ongoing, and the latest efficacy and safety data will be released in the future.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

H-M. Jing.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.