Venetoclax plus dose-adjusted R-EPOCH (VR-DA-EPOCH) or G-EPOCH bridging to subsequent cellular therapy for the patients with transformed lymphoma a single center clinical experience.

Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4-29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.

Case report: Identification of atypical mantle cell lymphoma with CCND3 rearrangement by next-generation sequencing.

The t(11;14) (q13;q32) translocation resulting in overexpression of cyclin D1 is the major oncogenic mechanism in mantle cell lymphoma (MCL). Most MCLs can be diagnosed based on morphological features, cyclin D1 expression, and IGH/CCND1 rearrangement. However, in some atypical cases where conventional FISH studies fail to detect IGH/CCND1 rearrangement or immunohistochemistry for cyclin D1 is negative, the diagnosis of the disease can be difficult. Hence, next-generation sequencing (NGS) may allow the identification of molecular alterations and assist in the diagnosis of atypical MCL. In this study, we reported a case of a patient diagnosed as asymptomatic MCL who presented with lymphadenopathy during the initial assessment. A lymph node biopsy was performed and the results revealed a high Ki67 index. However, initial diagnosis of aggressive MCL was difficult since the IGH/CCND1 rearrangement result was negative. Ultimately, by the aid of NGS we identified a rare CCND3 rearrangement in the patient, which lead to overexpression of cyclin D3, thereby facilitating the diagnosis of MCL.