Anti-CD38 Monoclonal Antibody Daratuzumab Improve Responses to Chemotherapy-Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): A Case Report
Authors: LI Xiaoqing , An Gang , Du Xin , Chen Weihong 
Published: November 2020

Background
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) accounts for 0.44% of hematologic malignancies and is a rare aggressive myeloid neoplasm which shows high rates of cutaneous lesions, bone marrow involvement and lymphadenectasis. Central nervous system (CNS) recurrence can occur when disease progress, preventative intrathecal treatment was essential, whereas optimal treatment of relapsed or refractory BPDCN is still poorly defined.
Since a transmembrane glycoprotein, CD38, was defined as a cell receptor which is express not only on lymphoid tissues but also on myeloid cells, Daratumumab (Dara) , the first-in-class human-specific anti-CD38 IgG1 mAb approved for the treatment of MM, had been currently reported to use in treating other hematological malignancies such as Acute Promyelocytic Leukemia (APL), T-acute lymphoblastic leukemia and BPDCN.
Case presentation
A 66-year-old male patient was admitted to hospital due to fatigue and palpitation, no cutaneous lesion and B symptoms were presented. Physical examination showed painless enlarged lymph nodes on neck, armpits and groin from multiple bilateral. Blood routine: WBC 2.18×109/L, HGB 83g/L, PLT 57×109/L. Bone marrow aspiration showed 79.5% of unclassified cells with irregular nuclei and immature chromatin pattern. Flow cytometry showed 82.26% abnormal cells were positive for CD56,CD123,CD38,CD303,CD304,TCL-1,CD5,CD4. Fluorescence in situ hybridization(FISH) showed P53/CEP17 1.2% positive on amplification, while chromosome showed normal karyotype. Next Generation Sequencing(NGS): TET2/JAK1/KMT2D/PHF6/TP53 mutation. BPDCN of stage Ⅳ/group A was diagnosed.
Induction regimen VDCAP was suspended because the patient suffered from infection and grade IV cytopenia on the 3rd day of chemotherapy. Then 7 cycles of CDOP with 5 months of oral BCL-2 inhibitor Venetoclax were applied, autologous stem cell cryopreservation was conducted in the 4th to 5th cycle chemotherapy interval. Bone marrow aspiration after 8 cycles indicated that the patient received bone marrow complete remission, however minimal residual disease test harbored 0.65% abnormal dendritic cells. The patient suffered from headache and sight lost due to disease central nervous system (CNS) recurrence during preparation of autologous stem cell transplantation. The CNS relapse was confirmed by lumbar puncture, the cerebrospinal fluid White blood cell count is 278 x10e6 copies/L and flow cytometry testing for these abnormal white cells was in accord to BPDCN phenotype, meanwhile BM morphology showed 48% of abnormal dendritic cells of typical BPDCN immunophenotype with CD38 expression by flow cytometry either. After treatment with Two cycles of Daratuzumab-VRd regimen and one cycle of HD-MTX(3g/m2) in addition to Temolozomide 140mg/d for 7 days, the disease re-assessment was done, bone marrow aspiration showed 10% residual tumor cells, the amount of WBC in CSF reduced to 14 x10e6 copies/L. Therapeutic response reached Partial Remission (PR) and the patient's state is good.
Conclusion
BPDCN is rare, therefore no standard treatment was the first-in-class recommendation. Regimens for ALL, AML and NHL had been used for the induction therapy. Although remission rate of ALL regimens are as high as 90%, the duration of response was short, with a median survival of only 12-14 months. Targeted therapy like BCL-2 inhibitor Venetoclax, CD38 monoclonal antibody Daratuzumab and CD123-direct cytotoxin Targraxofusp had been reported to be sensitive to disease. This is the secondly reported case that treated with Daratuzumab. All two cases seemed to be effective. Currently, there is no standardized treatment for BPDCN, novel targeted therapies may improve the prognosis of BPDCN in the near future. This case also indicating that CD38 CART therapy also might be rational for the treatment on myeloid neoplastic.

Disclosures
No relevant conflicts of interest to declare.