{"doi":"10.1111/bjh.70209","title":"First‐line tagraxofusp induces durable responses with prolonged survival in adults younger than 50 years with blastic plasmacytoid dendritic cell neoplasm: Post hoc analysis of a phase 2 trial","abstract":"To the Editor, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive and orphan haematological malignancy that expresses CD123 and other markers, presents in the skin, bone marrow (BM), blood and viscera.1, 2 Although the median age of patients at diagnosis is 67 years old, BPDCN can occur at any age and has a bimodal incidence with peaks seen in both those younger than 20 years and those older than 60 years.3-5 Data are limited on the management of BPDCN in patients <50 years, including the adolescent and young adult population defined as 15–39 years old in oncology studies.6, 7 Tagraxofusp, a first-in-class CD123-targeted therapy, is the only drug with regulatory approval for adults and children ≥2 years with treatment-naive or relapsed/refractory BPDCN in the United States8 and for adults with treatment-naive BPDCN in Europe.9 These approvals were supported by results from a pivotal, multicentre phase 2 study (NCT02113982) prospectively designed with prespecified, multisystem response criteria.10, 11 The 65 patients with BPDCN treated with first-line tagraxofusp (12 μg/kg once daily on days 1–5 of a 21-day cycle) in the pivotal study had a 75% overall response rate (ORR) and a 57% complete response (CR)/clinical CR (CRc; CR with residual skin abnormalities not indicative of active BPDCN) rate, with rapid and durable responses (median time to response: 23 days; median time to CR/CRc: 39 days; median duration of CR/CRc: 24.9 months).11 Tagraxofusp has a well-characterized and manageable safety profile with adverse events (AEs) being transient, occurring mostly in cycle 1, no cumulative long-term toxicity and no myelosuppression.11 The majority of patients have restoration of normal haematopoiesis at the end of cycle 1 irrespective of baseline BM involvement.12 While not approved, multi-agent induction chemotherapy has been used in young adult patients with BPDCN, resulting in short- and long-term toxicity, including prolonged myelosuppression.13-15 Therapeutic options that are more effective and without these long-term toxicities are needed to help patients achieve responses and more safely bridge to a potentially curative haematopoietic stem cell transplantation (HSCT). To evaluate the safety and efficacy of tagraxofusp in younger people with BPDCN, we performed a post hoc subgroup analysis of the pivotal study.10, 11 The pivotal study design, patient selection criteria and methods have been previously reported.10, 11 For this post hoc analysis, we analysed outcomes in adults 18–49 years with BPDCN prospectively treated with first-line tagraxofusp. Analysed outcomes included best objective response, time to best response, duration of response (DOR), overall survival (OS), bridging to HSCT and treatment-related AEs (TRAEs), including capillary leak syndrome (CLS). Patient baseline demographic and clinical characteristics were summarized, and descriptive statistics, such as median (range) and number of patients (percentage), were used for post-treatment outcomes. Ten patients aged <50 years were identified from the pivotal study and included in the analysis. The median age was 32 years (range, 22–45; Table 1), and the population included six young adults (age range, 22–32 years). All patients had an Eastern Cooperative Oncology Group performance status of 0 (80%) or 1 (20%). The most common sites of disease were skin (100%) and lymph node (60%); 60% of patients had ≥2 sites of disease. One patient (a 40-year-old woman) had a prior haematological malignancy (Hodgkin lymphoma). Patients received a median of 4 (range, 2–7) cycles of tagraxofusp. During the first cycle, patients received a median of five doses (range, 3–5), in line with the prescribed dosing.8, 9 At a median follow-up of 34 (range, 10–53) months, two CRs, five CRcs and one partial response (PR) were observed for an ORR of 80% (Figure 1A). The median time to response was 21 (range, 14–44) days, and the median DOR was not reached (NR; range, 0.9–51.8 m","journal":"British Journal of Haematology","year":2025,"id":529069,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":75579,"name":"Andrew A. Lane","orcid":"0000-0001-7380-0226","position":1,"is_corresponding":false},{"id":233355,"name":"Kendra Sweet","orcid":"0000-0001-6248-3317","position":2,"is_corresponding":false},{"id":542792,"name":"Sumithira Vasu","orcid":"0000-0002-8635-3880","position":3,"is_corresponding":false},{"id":1407823,"name":"Alessandra Tosolini","orcid":null,"position":4,"is_corresponding":false},{"id":1407824,"name":"John Katsetos","orcid":null,"position":5,"is_corresponding":false},{"id":18373,"name":"Marina Konopleva","orcid":"0000-0002-9347-2212","position":6,"is_corresponding":false},{"id":232838,"name":"Naveen Pemmaraju","orcid":"0000-0002-1670-6513","position":7,"is_corresponding":false},{"id":89270,"name":"Anthony S. Stein","orcid":"0000-0002-1786-1398","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T02:50:52.565868Z","pmid":"41077812","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}