HCVAD Chemotherapy Treatment Regimen Shows Promise for Blastic Plasmacytoid Dendritic Cell Neoplasm

Naveen Pemmaraju, MD, inaugural director of the BPDCN program and associate professor in the department of leukemia, division of cancer medicine at the University of Texas MD Anderson Cancer Center in Houston, and colleagues conducted the study. In spite of these higher CR rates, HCVAD did not result in longer remission times or survival rates for BPDCN, a rare blood cancer that also involves the skin, central nervous system (CNS) in 20-30% of patients, and immune cells, researchers reported.¹ BPDCN is more common in older men, and has a poor prognosis. Treatment regimens are under investigation, with SL-401 (tagraxofusp) recommended as a first-line therapy.

“Most patients are not cured outside of hematopoietic stem cell transplant (HSCT), and central nervous system (CNS) relapses are now emerging commonly in the modern targeted therapy era of BPDCN,” researchers wrote. They said that combined therapies with both targeted and cytotoxic chemotherapy that include treatment that prevents involvement of the CNS are needed as soon as possible.¹

One hundred BPDCN patients from the University of Texas MD Anderson Cancer Center whose diagnosis was confirmed by expert pathology review participated in the study. The single-institution study was conducted between 1999 to 2020. The study outcome compared CR and overall survival rates in patients who received HCVAD versus those who had non-HCVAD treatment. Researchers collected information about patient demographics, cancer history, specific disease mutations, the involvement of bone marrow, and serologic testing.¹ Study participants were divided into 3 groups. Thirty-five patients were in the frontline HCVAD-based therapy (median diagnosis age 61), either alone or in combination with other therapies:

• HCVAD alone (23)
• HCVAD + venetoclax (4)
• mini-HCVAD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses) + venetoclax, with or without enasidenib (2)
• HCVAD + bortezomib (2)
• modified HCVAD (1)
• HCVAD + SL-401 (tagraxofusp-erzs), with or without venetoclax (3)¹

Thirty-seven patients were in an SL-401 (tagraxofusp) group (median diagnosis age 68), which is a genetically modified diphtheria toxin fused with interleukin-3; and 28 patients (median diagnosis age 65) were given other regimens. Researchers performed a retrospective analysis between 1999-2020 to compare remission and survival rates among the different treatment groups.

Patients in the HCVAD-based regimens had higher rates of CR (80%) followed by SL-401 (tagraxofusp) patients (59%).¹ The group following other regimens had the lowest rate at 43%.¹ Researchers reported no significant difference in overall survival rates: the HCVAD group averaged 28.3 months, the SL-401 group averaged 13.7 months, and the other regimens group averaged 22.8 months. Pemmaraju and colleagues also said there was no significant difference in remission duration probability (38.6 for HCVAD vs not reached vs 10.2 months.¹ Researchers reported that HSCT was performed in 51% (HCVAD) vs 49% (SL-401) vs 38% (other regimens) for each group.¹

“These results suggest a continued important role for HCVAD-based chemotherapy in BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting,” Pemmaraju and colleagues said.¹ They added that additional ongoing studies are examining the safety, clinical feasibility, and activity of 2 and 3 combination options of targeted therapies with cytotoxic agents with the hope of inducing remission for the long-term.¹ Researchers noted for next steps, they are studying “triplet combination with HCVAD as a comprehensive combination therapy protocol for BPDCN that includes the 3 most active regimens, CD123, BCL-2, and ALL-based cytotoxic approach with SL-401/venetoclax/HCVAD, in addition to intrathecal chemotherapy for CNS prophylaxis.”¹

Reference

1. Pemmaraju N, Wilson NR, Garcia-Manero G, et al. Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD. Blood Adv. 2022;6:3027-3035. doi:10.1182/bloodadvances.2021006645.