P1, N=43, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

P2, N=76, Not yet recruiting, Stemline Therapeutics, Inc. | Initiation date: Aug 2024 --> Nov 2024

This case emphasizes the challenges of diagnosing and treating BPDCN, noting its rarity and absence of standard therapy. Tagraxofusp has shown promising results but presents safety concerns like capillary leak syndrome, particularly in elderly patients with comorbidities.

P1, N=39, Not yet recruiting, Aptevo Therapeutics

P1, N=50, Not yet recruiting, LAVA Therapeutics N.V.

P1/2, N=169, Recruiting, Sanofi | N=126 --> 169 | Trial completion date: Nov 2026 --> Oct 2030

P1, N=130, Recruiting, MacroGenics | N=90 --> 130 | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> Oct 2025

P1, N=30, Recruiting, Affimed GmbH | Active, not recruiting --> Recruiting

Currently, standard treatment strategies include clinical trials; chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD); and tagraxofusp-erzs (TAG, previously SL-401) which is the first-in-class targeted therapy against CD123...However, despite promising results, there are still patients who may be resistant to TAG monotherapy and/or who respond but eventually relapse. Herein, we discuss an important patient case of BPDCN treated with TAG and review BPDCN treatment strategies.

P1, N=3, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Completed | N=16 --> 3 | Trial completion date: Dec 2027 --> Jun 2024 | Trial primary completion date: Dec 2025 --> Jun 2024

P1/2, N=20, Not yet recruiting, Stanford University

P2, N=3, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; The protocol was terminated early due to slow participant accrual and the sponsor not willing to provide the study drug.

P2, N=11, Terminated, Washington University School of Medicine | Trial completion date: Mar 2026 --> Jul 2024 | Active, not recruiting --> Terminated; The sponsor is no longer supporting the drug

P1/2, N=4, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=40 --> 4

P2, N=11, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=25 --> 11 | Trial completion date: Jun 2029 --> Mar 2026 | Trial primary completion date: Jul 2028 --> Mar 2024

P1/2, N=18, Recruiting, Sanofi

P1, N=43, Not yet recruiting, City of Hope Medical Center

P1, N=24, Active, not recruiting, Affimed GmbH | Recruiting --> Active, not recruiting | N=50 --> 24

P2, N=76, Not yet recruiting, Stemline Therapeutics, Inc.

P1, N=72, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: May 2024 --> May 2025

P2, N=25, Recruiting, Washington University School of Medicine | Trial completion date: Dec 2027 --> Jun 2029 | Trial primary completion date: Jan 2026 --> Jul 2028

P1, N=20, Not yet recruiting, University of Kansas Medical Center

These studies show that the multispecific-targeting strategy used with MP0533 holds promise for improved selectivity towards LSCs and efficacy against clonal heterogeneity, potentially bringing a new therapeutic option to this group of patients with high unmet need. MP0533 is currently being evaluated in a dose-escalation phase 1 study in patients with relapsed or refractory AML (NCT05673057).

In line with results from 13 published cases outside clinical trials in the literature, sustained responses were associated with CR after tagraxofusp treatment and subsequent alloHCT. Our results provide real-world evidence for safety and efficacy of tagraxofusp as first-line treatment for BPDCN.

P2, N=53, Recruiting, Joshua Zeidner | Not yet recruiting --> Recruiting

Responses only occurred in Cohort B, with a partial response in one patient with Hodgkin's lymphoma and morphological complete remission in the bone marrow in one patient with blastic plasmacytoid dendritic cell neoplasm. In conclusion, flotetuzumab had a manageable safety profile in advanced CD123-positive hematological malignancies.

The successful targeting of CD123 in BPDCN has also encouraged research into a variety of other CD123-positive hematological neoplasms, including acute myeloid leukemia (AML), and informed the development of other novel agents targeting CD123. This review examines the clinical data leading to the development and approval of tagraxofusp in BPDCN, how it is being used in combination to improve outcomes in BPDCN and AML, and its developing role in other hematological malignancies.

No abstract available

P1, N=0, Withdrawn, Jonsson Comprehensive Cancer Center | N=29 --> 0 | Not yet recruiting --> Withdrawn

In addition, we present best practices and real-world insights from clinicians in academic and community settings in the US on how they use tagraxofusp to treat BPDCN. Several case studies illustrate the efficacy of tagraxofusp and discuss its safety profile, as well as the prevention, mitigation, and management of anticipated adverse events.

Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy.

P1, N=36, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting | Phase classification: P1a/1b --> P1

The advent of tagraxofusp has opened a new era of precision oncology in the treatment of BPDCN. Herein, we present an overview of BPDCN biology, its diagnosis, and treatment options, illustrated by clinical cases.

The patient showed resistance to Tagraxofusp and Venetoclax, and he died about 16 months after diagnosis. Considering the predicted effect of the AFF4::IRF1 fusion on IRF1's antitumor effects and immune regulation, and the possibility of its relevance to the aggressive course observed in this case, we propose further evaluation of the clinical significance of this fusion in BPDCN in future cooperative group studies and the consideration of therapeutic strategies aimed at restoring IRF1-dependent antineoplastic effects in such cases.

P1, N=12, Recruiting, Peking University People's Hospital

BPDCN is a rare and challenging entity sharing various typical characteristics of other hematological diseases. Comprehensive diagnostics should be initiated timely to ensure appropriate treatment strategies.

P1, N=13, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2023 --> May 2026 | Trial primary completion date: Nov 2023 --> May 2026

P1, N=16, Active, not recruiting, Children's Oncology Group | N=47 --> 16 | Trial completion date: Oct 2023 --> Sep 2024

P2, N=53, Not yet recruiting, Joshua Zeidner

Median overall survival and progression-free survival were 14 months (95% CI, 9.5-NA) and 8.5 months (95% CI, 5.1-NA), respectively. In summary, TAG-AZA-VEN shows encouraging safety and activity in high-risk AML, including TP53-mutated disease, supporting further clinical development of TAG combinations.

Therapy prior to allo-HCT included hydroxyurea and TAG + venetoclax + mini-HyperCVAD for 5 cycles. This case report demonstrates a patient experiencing a clinically meaningful benefit with TAG maintenance therapy after allo-HCT. Both prolonged survival and manageable safety, in this case, highlight the feasibility of long-term TAG maintenance post-allo-HCT to control BPDCN.

The role of the JAK/Signal transducer and activator of transcriptions (STAT) pathway in MF has led to the recent approval of three different JAK2 inhibitors (ruxolitinib, pacritinib, and fedratinib) for MF treatment. Our studies showed high sensitivity of MF cell lines to tagraxofusp as a single agent, which is expected given phase 2 results demonstrated clinical efficacy of single-agent tagraxofusp in R/R MF (Yacoub et al. ASH 2021). In addition, synergism was observed in combination with JAK inhibitors.