BV-CHP in Previously Untreated Patients with CD30-Positive Adult T-Cell Leukemia-Lymphoma: A Multicenter Real-World Retrospective Study

Background: Adult T-cell leukemia-lymphoma (ATL) is defined as peripheral T-cell lymphoma (PTCL) caused by the human T-cell leukemia virus type I and is endemic in Japan. ATL has high unmet medical needs due to its poor prognosis and limited treatment options. BV-CHP (brentuximab vedotin [BV], cyclophosphamide, doxorubicin, and prednisolone) was approved for previously untreated patients with CD30-positive PTCL in Japan in December 2019, but clinical data for patients with ATL are limited. This multicenter retrospective study aims to evaluate the efficacy and safety of BV-CHP for previously untreated patients with CD30-positive ATL. Methods: We retrospectively collected clinical data from the medical records of patients from 6 sites in Japan between April 2020 and January 2024. Patients aged ≥18 years with previously untreated CD30-positive ATL treated with BV-CHP were enrolled. CD30 positivity was determined by immunohistochemistry or flow cytometry at each institution. The primary endpoint was the overall response rate (ORR) for BV-CHP. Adverse events (AEs) were collected from the initiation of BV-CHP to 4 weeks after the last administration of BV-CHP. This study was conducted in accordance with Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Results: A total of 46 patients were enrolled in this study. Of these, 36 patients who met the eligibility criteria and did not receive BV-CHP in a clinical trial were analyzed. The median age at diagnosis was 71 years (range, 53-92), and 24 were female. Nineteen patients were classified as acute-type and 17 as lymphoma-type. Thirty-two patients were at advanced stage (9 at Stage III and 23 at Stage IV). For the simplified ATL prognostic index, 11, 19, and 6 patients were categorized as low-, intermediate-, and high-risk, respectively. The median cycle of BV-CHP was 3 (range, 1-6) and the relative dose intensity of BV was 86.9% (range, 57.8-123.5). The median follow-up time was 372.5 days (range, 74-1253). The ORR was 86.1% (95% confidence interval [CI], 70.5-95.3), including 10 (27.8%) complete responses (CR), 12 (33.3%) CR unconfirmed, and 9 (25.0%) partial responses (PR). The median progression-free survival (PFS) was 205 days (95% CI, 166-279), and the time to treatment failure was 166 days (95% CI, 91-205). The median overall survival was 535 days (95% CI, 343-not reached). Grade 3 or higher toxicities were observed in 32 patients. The most common grade 3 or higher AEs, occurring in >10% of patients, were neutropenia (77.8%), febrile neutropenia (38.9%), infection (25.0%), and decreased platelet count (11.1%). Among all 36 patients, 7 discontinued BV, and 1 had their dosage of BV changed due to AEs. Peripheral neuropathy (PN) events were identified in 4 patients (3 with grade 2 and 1 with grade 1), and 1 of these 4 patients had their treatment dosage of BV changed due to PN. All AEs were resolved or improved, and there were no treatment-related deaths. Of the 36 patients, 11 received allogenic stem cell transplantation (10 cord blood and 1 peripheral blood). The disease status before transplantation was 2 CR, 8 PR, and 1 stable disease following a median of 3 cycles of BV-CHP (range, 1-6). Acute graft-versus-host disease was observed in 2 of 11 patients, including grade 1 in 1 patient and grade 4 in 1 patient. The median PFS after initiation of BV-CHP was 234 (95% CI, 168-343) and 180 (95% CI, 96-279) days in transplanted and non-transplanted patients, respectively. Conclusion: In this multicenter retrospective study, BV-CHP demonstrated a favorable ORR with acceptable tolerability. All AEs were manageable, and no new safety signals were observed. These data support BV-CHP as a potential standard first-line therapy for ATL.