Mechanism of Action and Potential Efficacy of Tagraxofusp

EP: 1.Overview of BPDCN

EP: 2.Initial Therapy Selection and Considerations

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EP: 3.Mechanism of Action and Potential Efficacy of Tagraxofusp

EP: 4.Clinical Trial Data on Tagraxofusp

EP: 5.Potential of Anti-CD123 CAR T-Cell Therapy

EP: 6.Adverse Event Monitoring and Management

EP: 7.Quality of Life Considerations for BPDCN Management

EP: 8.Future Landscape of BPDCN Management

Clinical Presentation:

A 67-year-old man referred from dermatologist.

Referred initially to dermatologist by PCP for progressive, persistent, cutaneous nodules that patient first noticed 3 weeks prior

Initial Clinical Workup and Diagnosis:

ROS: Fatigue, 5 kg weight loss over 3 moths

PMH: Sinusitis; no major comorbidities

PE: Notable for multiple purpuric nodules (measuring up to 5 cm on arms, legs, torso). No palpable adenopathy, hepatosplenomegaly

ECOG PS =1

Labs: WBC 14.1 x 103/uL, Hb 8.9 g/dL, platelets 54 x 103/uL. Differential revealed 12% blasts, 32% neutrophils, 16% monocytes, 40% lymphocytes.

Skin: purpuric nodule

Peripheral blood smear: blastic cells with large and round or slightly irregular nuclei; blast cytoplasm stained greyish blue without granules or Auer rods

Bone marrow biopsy showed 40% blasts by morphology; 80% cellular marrow with interstitial infiltrate.

IHC of neoplastic cells: CD123, CD4, CD56, TCL1 positive

Flow cytometry:

CD4, CD56, CD123 were positive;

CD34 and T- and B-cell lineage-specific markers were negative

Cytogenetics: 46 XY

Lumbar puncture did not indicate CNS involvement

The patient was ultimately diagnosed with BPDCN based on clinical and histopathological findings.

Initial Treatments:

Tagraxofusp initiated:

Initial dose 12 mcg/kg as per package label for frontline therapy and achieves CR after 1 cycle of therapy.