Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, very aggressive type of leukemia. In contrast to other types of fast-growing acute leukemias, patients with BPDCN often develop characteristic violaceous skin tumors in addition to more typical bone marrow, blood, and lymph node involvement. Until recently, given its rarity, BPDCN received little attention from doctors and scientists, and few treatment options were available. That is now changing, with major contributions from Andrew Lane, MD, PhD, director of Dana-Farber's BPDCN Center, which leads clinical and lab research efforts focused on BPDCN.
As a hematology/oncology fellow, Lane recognized that patients with BPDCN experienced poor outcomes when treated with chemotherapy designed for lymphomas and acute myeloid leukemia (Taylor et al. Blood 2019; 134:678-687). After joining Dana-Farber's leukemia program as faculty, Lane helped successfully develop tagraxofusp, the first FDA-approved drug for BPDCN (Pemmaraju, Lane et al. N Engl J Med 2019; 380:1628-37). Currently, the BPDCN center is focused on spurring further breakthroughs through its clinical trial portfolio, which offers patients access to the latest novel treatment approaches for this disease (protocol 17-056, protocol 18-045), while collaborating closely with bench scientists like Lane seeking better understanding of BPDCN disease biology.
Lane and colleague Marlise Luskin, MD, MSCE, another BPDCN expert in the leukemia group, are excited to have opened the first cellular therapy protocol at Dana-Farber testing chimeric antigen receptor (CAR) T cells for BPDCN (protocol 19-544). Lane and Luskin worked closely with the trial sponsor (Mustang Bio) to design the protocol, and are optimistic it will serve BPDCN patients who have not responded to prior therapies. In contrast to the CAR T cells approved for lymphomas which target CD19, a lymphoid marker not expressed on BPDCN tumor cells, the Mustang Bio CAR T-cell product targets CD123, a component of the interleukin-3 receptor (IL-3R), a protein universally and highly expressed on BPDCN cells, making it an ideal target for the disease.
This protocol is part of a robust CAR T-cell portfolio managed by our Adult Leukemia Program in collaboration with our Immune Effector Cell Therapies Program, which also includes two trials for adults with B-cell ALL [AUTO1, an autologous CAR T-cell treatment targeting CD19 (protocol 20-272) and UCART22, an allogeneic CAR T-cell treatment targeting CD22 (protocol 20-562)] and acute myeloid leukemia (UCAR123, an allogeneic CAR T-cell treatment targeting CD123, protocol 18-233). Our Adult Leukemia, BPDCN, and Immune Effector Cell Therapies programs are poised to contribute to advances in cellular immunotherapy for patients with BPDCN, acute lymphoblastic leukemia, and acute myeloid leukemia.
