^
2d
Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report of a Rare and Aggressive Hematologic Malignancy. (PubMed, Cureus)
Misdiagnosis or late diagnosis of this clinically heterogeneous BPDCN may lead to systemic spread and poor outcomes. Hence, prompt diagnosis and treatment are essential, with a multidisciplinary approach.
Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Elzonris (tagraxofusp-erzs)
7d
New P1 trial
|
CD123 targeted CAR-NK
24d
Enrollment open
|
azacitidine • Elzonris (tagraxofusp-erzs)
25d
Trial initiation date • Combination therapy
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
1m
Blast and Bursts: Unveiling Splenic Rupture in Blastic Plasmacytoid Dendritic Cell Neoplasia. (PubMed, J Community Hosp Intern Med Perspect)
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.
Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • TCF4 (Transcription Factor 4)
|
Elzonris (tagraxofusp-erzs)
1m
New P1 trial • Combination therapy
|
Venclexta (venetoclax) • azacitidine • mipletamig (APVO436)
2ms
New P1 trial
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
2ms
Enrollment change • Trial completion date
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
SAR443579
2ms
CP-MGD024-01: A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies (clinicaltrials.gov)
P1, N=130, Recruiting, MacroGenics | N=90 --> 130 | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> Oct 2025
Enrollment change • Trial completion date • Trial primary completion date
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression • IL3RA expression
|
MGD024
2ms
Enrollment open
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
|
AFM28
3ms
Overcoming Tagraxofusp-Erzs Monotherapy Resistance in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in a Real-World Clinical Setting. (PubMed, J Immunother Precis Oncol)
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.
Journal • Real-world evidence • Real-world
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Venclexta (venetoclax) • doxorubicin hydrochloride • cyclophosphamide • vincristine • Elzonris (tagraxofusp-erzs) • pivekimab sunirine (IMGN632)
3ms
Post-transplant Flotetuzumab for AML (clinicaltrials.gov)
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
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Post-transplantation
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
flotetuzumab (MGD006)
3ms
New P1/2 trial
|
cytarabine • cladribine • Elzonris (tagraxofusp-erzs)
4ms
Tagraxofusp in Treating Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm After Stem Cell Transplant (clinicaltrials.gov)
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.
Trial termination
|
Elzonris (tagraxofusp-erzs)
4ms
Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) (clinicaltrials.gov)
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
Trial completion date • Trial termination
|
flotetuzumab (MGD006)
4ms
Enrollment closed • Enrollment change
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Rituxan (rituximab) • cytarabine • cyclophosphamide • methotrexate • vincristine • leucovorin calcium • Truxima (rituximab-abbs) • Elzonris (tagraxofusp-erzs) • mercaptopurine • mesna • Hemady (dexamethasone tablets) • Neulasta (pegfilgrastim) • Neupogen (filgrastim) • Starasid (cytarabine ocfosfate)
4ms
Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) (clinicaltrials.gov)
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
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
|
flotetuzumab (MGD006)
4ms
New P1/2 trial
|
Venclexta (venetoclax) • azacitidine • SAR443579
4ms
New P1 trial
|
azacitidine • Elzonris (tagraxofusp-erzs)
5ms
First-in-Human Dose Escalation Study of AFM28 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=24, Active, not recruiting, Affimed GmbH | Recruiting --> Active, not recruiting | N=50 --> 24
Enrollment closed • Enrollment change
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
AFM28
5ms
New P2 trial • Combination therapy
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
5ms
Trial primary completion date • Combination therapy
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
6ms
Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) (clinicaltrials.gov)
P2, N=25, Recruiting, Washington University School of Medicine | Trial completion date: Dec 2027 --> Jun 2029 | Trial primary completion date: Jan 2026 --> Jul 2028
Trial completion date • Trial primary completion date
|
flotetuzumab (MGD006)
7ms
The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells. (PubMed, Cancer Immunol Res)
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).
Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CD70 (CD70 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
MP0533
7ms
Real-world evidence on tagraxofusp for blastic plasmacytoid dendritic cell neoplasm - collected cases from a single center and case reports. (PubMed, Front Oncol)
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.
Journal • HEOR • Real-world evidence • Real-world
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Elzonris (tagraxofusp-erzs)
7ms
Enrollment open
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
7ms
Flotetuzumab as a salvage immunotherapy in advanced CD123-positive hematological malignancies, a phase 1 pilot study. (PubMed, Leuk Lymphoma)
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.
P1 data • Journal • IO biomarker • Metastases
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
|
flotetuzumab (MGD006)
7ms
Tagraxofusp, a first-in-class CD123-targeted agent: Five-year postapproval comprehensive review of the literature. (PubMed, Cancer)
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.
Review • Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
|
Elzonris (tagraxofusp-erzs)
8ms
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CD38 (CD38 Molecule) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
BCL2 expression
|
Venclexta (venetoclax) • Darzalex (daratumumab) • Elzonris (tagraxofusp-erzs)
8ms
Tagraxofusp to Eradicate Measurable Residual Disease in Patients With Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=0, Withdrawn, Jonsson Comprehensive Cancer Center | N=29 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • CD123 expression • IL3RA expression
|
azacitidine • Elzonris (tagraxofusp-erzs)
9ms
Treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): focus on the use of tagraxofusp and clinical considerations. (PubMed, Leuk Lymphoma)
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.
Review • Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression • CD123 overexpression • IL3RA expression
|
Elzonris (tagraxofusp-erzs)
9ms
Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123. (PubMed, Int J Mol Sci)
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.
Review • Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs) • pivekimab sunirine (IMGN632)
10ms
GO-TAG: Tagraxofusp-erzs, an IL-3 Diphtheria Fusion Protein, in Combination With Gemtuzumab Ozogamicin in Patients With Relapsed/Refractory AML (clinicaltrials.gov)
P1, N=36, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting | Phase classification: P1a/1b --> P1
Enrollment open • Phase classification • Combination therapy
|
CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression
|
Mylotarg (gemtuzumab ozogamicin) • Elzonris (tagraxofusp-erzs)
10ms
Recent Advances in the Biology and CD123-Directed Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm. (PubMed, Clin Lymphoma Myeloma Leuk)
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.
Review • Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression
|
Elzonris (tagraxofusp-erzs)
10ms
Multiple Genomic Alterations, Including a Novel AFF4::IRF1 Fusion Gene, in a Treatment-Refractory Blastic Plasmacytoid Dendritic-Cell Neoplasm: A Case Report and Literature Review. (PubMed, Int J Mol Sci)
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.
Clinical • Review • Journal
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • AFF4 (AF4/FMR2 Family Member 4) • IRF1 (Interferon Regulatory Factor 1)
|
ASXL1 mutation • TET2 mutation • IRF1 expression
|
Venclexta (venetoclax) • Elzonris (tagraxofusp-erzs)
11ms
Off-the-shelf CD123 CAR-NK for R/R AML (clinicaltrials.gov)
P1, N=12, Recruiting, Peking University People's Hospital
New P1 trial
|
JD023
11ms
Diagnostic management of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in close interaction with therapeutic considerations. (PubMed, Ann Hematol)
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.
Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • CD7 (CD7 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Elzonris (tagraxofusp-erzs)
11ms
Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression
|
flotetuzumab (MGD006)
12ms
PEPN1812: Flotetuzumab for the Treatment of Pediatric Recurrent or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=16, Active, not recruiting, Children's Oncology Group | N=47 --> 16 | Trial completion date: Oct 2023 --> Sep 2024
Enrollment change • Trial completion date
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression • IL3RA expression
|
cytarabine • flotetuzumab (MGD006) • Starasid (cytarabine ocfosfate)
12ms
Trial completion date
|
IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive
|
azacitidine • Elzonris (tagraxofusp-erzs)
12ms
Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia. (PubMed, Blood Adv)
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.
P1 data • Journal • Combination therapy • IO biomarker
|
TP53 (Tumor protein P53) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
TP53 mutation • CD123 positive • IL3RA positive
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)