In this trial, tagraxofusp monotherapy in MF was well tolerated, without cumulative myelotoxicity, and with symptom score improvements, warranting further investigation in combination therapy. This trial was registered at www.clincaltrials.gov as #NCT02268253.

During tagraxofusp treatment, strict monitoring for early recognition of CLS symptoms and directed intervention is essential for managing CLS; with this approach CLS is typically mild and occurs mostly in cycle 1, without recurrence. We discuss patient selection and optimization, monitoring, and early intervention for successful identification and optimized management of CLS in real-world practice.

Given the poor prognosis associated with this subtype, CD123-targeted therapy, such as tagraxofusp-erzs, alone or in combination with agents like azacitidine and venetoclax, may represent a rational therapeutic approach. To our knowledge, this represents the third case report of RUNX1 rearrangement in pDC-AML and may provide valuable insights for future research.

P1, N=50, Terminated, LAVA Therapeutics N.V. | Recruiting --> Terminated

In acute myeloid leukemia relapse, downregulation of HLA class II on leukemic cells allows immune evasion, but this suppression can be reversed by IFN-γ or flotetuzumab, a CD123×CD3 bispecific antibody, restoring immunogenicity and potentially enhancing the graft versus leukemia (GVL) effect. Collectively, HLA class II molecules function not only in conventional antigen presentation to CD4+ T cells but also in neo-self antigen recognition, immune evasion, and tissue-specific disease expression. A deeper understanding of HLA class II biology may pave the way toward therapeutic strategies that separate GVHD from the GVL effect.

Tagraxofusp, a first-in-class CD123-directed antibody conjugate comprising human interleukin-3 and truncated diphtheria toxin, represents a welcome addition to the treatment armamentarium for BPDCN...Several questions remain unanswered-namely, the potential benefit of post-transplant consolidation or maintenance strategies to mitigate the risk of relapse or progression, and the role of next-generation sequencing as a prognostic tool and for better defining depth of remission and measurable residual disease, among others. We believe that further improvement in the prognosis of BPDCN will require large collaborative efforts, considering the rarity of this disease.

In this case series, we describe our institutional experience treating BPDCN both pre- and post-tagraxofusp approval. We summarize six cases, the majority of which occurred in elderly patients, and highlight unique challenges of treating BPDCN at a center that serves a large rural/frontier area with variable access to specialty care.

Tagraxofusp demonstrated a manageable safety profile with limited clinical efficacy in CMML. This trial was registered at www.ClinicalTrials.gov as #NCT02268253.

The differential prognosis of the mutation in various chromosomal and VAF settings will be explored. Lastly, we will outline therapeutic options, promising treatments on the horizon, and whether allogeneic stem cell transplant is curative.

P1/2, N=7, Terminated, Sanofi | N=18 --> 7 | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns

In addition, AFM28 is well tolerated and demonstrates pharmacodynamic activity in cynomolgus monkeys. Altogether, our results indicate that AFM28 has the potential to reduce relapse-inducing residual disease and promote long-term remissions for patients with AML and MDS with a favorable safety profile.

We demonstrated that the combination of CD123 T cell engager (SAR440234) and veTc boosted tumor specific T cell immunity and enhanced anti-leukemia effect in vitro...This effect was associated with an increase in cytotoxic T cell subsets and clonotypic expansion. Thus, the combination of T cell engager with adoptive T cell transfer of vaccine educated T cells is a novel approach that merits further investigation in clinical trials.