Menarini and Stemline will bring five ELZONRIS (tagraxofusp) data sets to ASH 2025, headlined by an oral Phase 2 readout of a triplet regimen with azacitidine and venetoclax in BPDCN that reportedly achieved high response and bridge-to-transplant rates with manageable tolerability. Additional presentations include a real-world analysis suggesting longer survival with tagraxofusp versus venetoclax in BPDCN, an oral registry study describing disease presentation and immunophenotype across 257 patients, a subgroup analysis indicating outcomes independent of baseline skin burden in the pivotal tagraxofusp trial, and an online-only report of tagraxofusp combined with low-intensity chemotherapy in CD123-positive relapsed/refractory AML.
The immediate news is an evidence refresh around a six-year-old U.S. approval and four-year EU approval. The triplet readout aims to position tagraxofusp not only as a monotherapy standard in BPDCN but as a combinational backbone that can deepen responses and facilitate transplant, the functional currency in this malignancy. The real-world comparison to venetoclax, widely used off-label in BPDCN and entrenched in AML care, signals an intent to counter practice drift and reinforce the rationale for CD123-directed therapy. The 257-patient registry and biomarker-focused characterization reflect an effort to tighten diagnostic capture and standardize phenotyping, prerequisites for both trial accrual and payer alignment.
Strategically, this is a defensive-consolidation move with expansion optionality. In BPDCN, where incidence and site experience are limited, practice is shaped by small datasets, expert consensus, and pragmatic constraints such as transplant access and toxicity management. Demonstrating that tagraxofusp can be safely layered onto azacitidine and venetoclax without jeopardizing transplant eligibility addresses a core tension: maximizing cytoreduction while preserving a path to curative intent. The real-world analysis, while non-randomized, is a direct challenge to the venetoclax-based regimens that have gained traction in older and frailer patients. The AML signal broadens the aperture to a larger market but will require disciplined biomarker strategies and careful safety choreography given overlapping toxicities and the known risk of capillary leak.
For sites, the operational load shifts toward combination management, transfusion support, and early transplant coordination. Centers will need robust CD123 testing workflows, consistent pathology criteria, and vigilant monitoring for capillary leak and hepatotoxicity alongside the myelosuppression inherent to azacitidine and venetoclax. CROs and cooperative groups could see increased demand for rare disease network trials, centralized diagnostic review, and hybrid evidence programs that integrate real-world endpoints. Regulators will scrutinize durability, early mortality, and safety in Cycle 1, and will expect cleaner comparative designs if sponsors seek label changes. Payers are likely to interrogate transplant conversion, hospitalization days, and supportive care utilization as proxies for value in a small-population setting.
The next inflection depends on the granularity of the ASH triplet data: complete response rates, depth of remission, time to transplant, 90-day mortality, and capillary leak incidence will determine whether this becomes a practice-guiding regimen or a hypothesis-generating signal. If the real-world survival advantage holds up under sensitivity analyses and better matching, expect a push toward compendia support and guideline reinforcement, with or without an immediate supplemental filing. In AML, the bar is higher; movement will require randomized or at least multi-arm signal-seeking studies with clear CD123-enrichment and predefined safety mitigation. Watch for sponsor decisions on a prospective comparative study versus venetoclax-based care, the build-out of centralized CD123 diagnostics, and alignment with transplant networks capable of rapid referral to fully translate combination gains into outcome improvements.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
