Anti-CD123-CAR T-cell therapy-radiotherapy combo effectively treats recurring blastic plasmacytoid dendritic cell neoplasm

A child with blastic plasmacytoid dendritic cell neoplasm recurrence post allogeneic hematopoietic stem cell transplantation achieved progression-free survival six months after receiving anti-CD123- chimeric antigen receptor (CAR) T-cell therapy followed by radiotherapy. The combination approach is effective for these patients who generally have a poor prognosis, according to a case report published online April 22, 2020 in OncoTargets and Therapy.¹

The 10-year-old male presented after experiencing five months of bilateral knee joint pain. A bone marrow smear and biopsy revealed the boy had blastic plasmacytoid dendritic cell neoplasm. Doctors treated him with two cycles of vincristine, liposomal doxorubicin, cyclophosphamide and prednisone chemotherapy, and two cycles of vincristine, liposomal doxorubicin, cytarabine and prednisone chemotherapy. The patient achieved complete remission after the chemotherapy regimen and didn’t receive allogeneic hematopoietic stem cell transplantation.

The patient presented with a scalp rash one month after his first complete remission in May 2018. Doctors diagnosed him with recurrent blastic plasmacytoid dendritic cell neoplasm.

The patient achieved a second complete remission after receiving this complex treatment regimen: one cycle of fludarabine, cytarabine and cyclophosphamide and two cycles of dexamethasone, vincristine, cytarabine, mitoxantrone and etoposide. Doctors followed that with two cycles of vincristine, dexamethasone, mitoxantrone and pegaspargase and two cycles of decitabine with aclacycin, cytarabine and granulocyte colony-stimulating factor. In January 2019, doctors followed that regimen with a father-to-son haploid allogenic hematopoietic stem cell transplant.

Still, the cancer recurred six months after the stem cell transplant.

Doctors then enrolled the patient in a clinical trial in which he received anti-CD123-CAR T-cells. The patient tolerated the anti-CD128 CAR T-cell therapy well. The proportion of anti-CD123- Car T-cells was 2.8% in the child’s peripheral blood 28 days after treatment.

“Because of the poor curative effect of anti-CD123-CAR T-cell therapy, we chose to perform radiotherapy 28 days after CART T-cell therapy when the CAR T cells were still at 2.8% in the peripheral blood,” the authors wrote. “Two weeks after his local radiotherapy, with the proportion of anti-CD123-CAR T-cells reaching a higher peak, the nodules on his head disappeared gradually.”

The authors reported that as they completed the paper, the patient had maintained progression-free survival with complete donor chimerism for six months post combination therapy.

Some background

There is no standard chemotherapy regimen for treating this rare hematopoietic cancer. Doctors commonly treat the cancer with acute myeloid leukemia-type , acute lymphoblastic leukemia-type or lymphoma-type chemotherapies.

Blastic plasmacytoid dendritic cell neoplasm progresses quickly and exhibits aggressive biological behavior. Patients’ median overall survival is 8.7 months, with allogeneic hematopoietic stem cell transplantation only extending median overall survival to 22.7 months.

Most patients have high expression of CD123 on their blastic plasmacytoid dendritic cell neoplasm cells. As a result, anti-CD123 CAR T-cell therapy is a promising treatment when blastic plasmacytoid dendritic cell neoplasm has recurred, according to the paper.

“In recent years, other treatments have been used for [blastic plasmacytoid dendritic cell neoplasm], especially for recurrent/refractory patients,” the authors wrote.

The new treatments for recurrent/refractory blastic plasmacytoid dendritic cell neoplasm include Elzonris (Tagraxofusp-erzs, Stemline), a CD123-directed cytotoxin FDA approved for the treatment of blastic plasmacytoid dendritic cell neoplasm in adults and in pediatric patients 2 years and older. Others are: “…daratumumab, which targets CD38 on tumor cells for only a few patients, pralatrexate, which is used for progression of [blastic plasmacytoid dendritic cell neoplasm], venetoxlax, which promotes tumor cell apoptosis, bortezomib, which downregulates NF-kB activyt, and 5ʹ-azacytidine, which reduces tumor cell methylation levels.” The authors wrote.

Disclosures: The authors report no relevant disclosures.

Reference: Jiang Y, Li Q, Yuan T, Jiang Y, Deng Q. Case Report of Anti-CD123 Chimeric Antigen Receptor T-Cell Therapy Followed by Radiotherapy for a Recurrence of Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem Cell Transplantation. Onco Targets Ther. 2020;13:3425-3430.