Venetoclax Combined with Dose-Adjusted R-EPOCH (VR-DA-EPOCH) As Treatment of Richter's Syndrome: A Real-World Study

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.4695-4695
• Main Authors: Zhu, Huayuan, Jiang, Rui, Shen, Hui, Wu, Wei, Yang, Yilian, Peng, Chen, Qiu, Jingyan, Ding, Chongyang, Shi, Chuanbing, Chen, Ruize, Wang, Li, Fan, Lei, Xu, Wei, Li, Jianyong
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-152483

Background: To evaluate the efficacy and safety of venetoclax, rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-DA-EPOCH) in Richter's syndrome (RS), we conducted a single-arm, retrospective, observational, real-world study in our center. Methods: Patients who had history of CLL/SLL were diagnosed as RS by biopsy during treatment or watch and wait strategy. VR-DA-EPOCH was given as follow, venetoclax was administered with accelerated ramp-up from 20 mg per day to 400 mg per day, d1-10 during cycle 1, 400 mg daily on day1-10 of cycle 2-6, rituximab 375 mg/m 2 on day 0 of cycle 1 and 500 mg/m 2 on day 0 of cycle 2-6, plus etoposide (50 mg/m 2,day1-4), vincristine (0.4 mg/m 2 day 1-4) or vindesine 3 mg/m 2 day 1 , doxorubicin (10 mg/m 2 day 1-4), prednisone (60 mg/m 2, day 1-5), cyclophosphamide (750 mg/m 2 day 5), 21 days per cycle，dose adjustment on the basis of nadir ANC and platelet count are as previously reported by Wison WH. Response assessment was conducted after 2 or 3 cycles by enhanced CT or PET/CT and after 6 cycles (EOT) by PET/CT according to 2014 Lugano criteria. Minimal residual disease (MRD) of CLL cell in peripheral blood (PB) and bone marrow (BM) was detected after 2 or 3 and 6 cycles by flow cytometry. uMRD was defined as less than 1 CLL cell per 10 4 leukocytes. Results: 7 RS patients were enrolled in Pukou CLL Center from 10/2019 to 7/2021 and the last follow up was 07/25/2021. The median age was 52 years old. Unmutated IGHV, complex karyotype (CK) and TP53 deletion and/or mutation was detected in 100% (6/6), 20% (1/5) and 40% (2/5) patients, respectively. 5 patients received at least one prior line (range: 1-5) treatment for CLL/SLL, with 4 patients received ibrutinib as last prior therapy and one patient previously exposed to venetoclax. 2 patients were diagnosed as RS during watch and wait. The median duration from diagnoses or previous treatment for CLL/SLL to RS was 12 months (range: 3-14). All patients underwent lymph node (n=6) or bone biopsy(n=1) at the site of SUVmax or secondary SUV uptake (unaccessible for SUVmax) by PET/CT and was confirmed as transformed to non-GCB type of diffuse large B-cell lymphoma (DLBCL). Furthermore, 4 of 4 (100%) available patients were confirmed as clonal-related RS by detecting IGHV gene usage. 3 patients acquired CK, and 2 patients appeared BTK C481S mutation. 7 patients completed at least 2 cycles and were available for efficacy and safety ass