Brentuximab vedotin plus DHAP as effective salvage therapy in CD30+ peripheral T-cell lymphoma: A retrospective multicenter study

Abstract The prognosis of most nodal peripheral T-cell lymphomas (T-NHL) has not significantly improved over the past 25 years. Stage- or IPI-dependent 5-year overall survival (OS) rates remain around 30%. Recently, for the first time, a significant OS benefit was demonstrated for the combination of brentuximab vedotin (BV) and CHP (cyclophosphamide, doxorubicin, prednisone) compared to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line treatment of patients with anaplastic large cell lymphoma (ALCL). However, approximately 30% of patients with peripheral T-NHL experience a disease course that is primarily refractory, with dismal prognosis. BV monotherapy achieves high remission rates, particularly in relapsed ALCL, but also in other relapsed T-NHL subentities. For relapsed/refractory (R/R) nodal peripheral T-NHLs other than ALCL, only conventional (multi-agent) chemotherapy is approved by both the European Medicines Agency as well as the Food and Drug Administration, while single-agent BV is approved for R/R ALCL only. Effective treatment options for younger patients with high remission rates for curative intended treatment concepts are urgently needed. In Hodgkin lymphoma, the addition of BV to DHAP (dexamethasone, high-dose cytarabine, cisplatin) has shown promising efficacy as a salvage regimen in a phase II trial. Based on this, we conducted a multicenter retrospective analysis based on the national T-NHL registry platform of the GLA and OSHO study groups to evaluate the efficacy and tolerability of platinum-based salvage therapies in combination with BV in patients with R/R T-NHL. A total of 26 patients treated with either BV-DHAP or BV-ICE between 2015 and 2025 were identified. Median age at diagnosis was 55 years (range 23–77), and 11/26 patients (42.3%) were female. Histologic subtypes included ALCL (11/26, 42.3%), angioimmunoblastic T-cell lymphoma, T-NHL not otherwise specified, enteropathy-associated T-cell lymphoma, and systemic primary cutaneous T-NHL. Most lymphoma expressed CD30 (22/26; 84,6%), 1/26 (3,9%) was assessed as CD30-negative and for 3/26 patients (11,5%) the information was not available. Median number of prior treatment lines was 2 (range 1-7). Eight out of 26 patients (30.8%) had previously received BV, and 4/26 (15.4%) had undergone prior autologous stem cell transplantation. Most patients (24/26, 92.3%) were refractory to the previous therapy or had relapsed within one year. Fourteen patients received BV-ICE, and 12 received BV-DHAP as salvage therapy. Best overall response rate (ORR) in the entire cohort was 53.9% (14/26), including CR in 6/26 (23.1%) and PR in 8/26 (30.8%). In the BV-ICE subgroup, ORR was 35.7% (5/14; CR 1/14 [7.1%], PR 4/14 [28.6%]). In contrast, the BV-DHAP subgroup demonstrated an ORR of 83.3% (10/12; CR 5/12 [41.7%], PR 5/12 [41.7%]). Among BV-DHAP patients, 8 had ALCL and 4 had other T-NHL subtypes. All non-ALCL patients (4/4) and 6/8 (75%) of ALCL patients responded to BV-DHAP. In the BV-ICE group, 3 patients had ALCL and 11 had other T-NHLs; responses were seen in 3/11 (27,3%) non-ALCL patients and 2/3 (66,7%) ALCL patients. Toxicities were manageable, comparable between regimens and primarily included grade 3/4 hematologic adverse events in 18/21 patients (85,7%), febrile neutropenia in 13/21 patients (61,9%), and transient liver enzyme elevations in 20/23 patients (87%). No new cases of peripheral neuropathy were documented. In conclusion, BV-DHAP was particularly effective as a salvage regimen in this high-risk cohort of R/R CD30-positive T-cell non-Hodgkin lymphoma, with manageable toxicity. Further studies are warranted to establish its superiority over BV monotherapy in this setting.