Efficient Targeting of CD38 in Mature T-Cell Neoplasms with Daratumumab and Allogeneic NK Cells

Introduction: Mature T-cell neoplasms (MTCN) are a heterogeneous and aggressive group of lymphoid neoplasms with very limited options for precision immunotherapy. Targeted immunotherapy with antibodies directed against surface markers on tumor cells has emerged as an effective treatment for B-cell neoplasms, but the development of immunotherapy strategies for MTCN has been much slower. CD38 is expressed at low levels in a subset of normal resting T-cells. Data on the frequency and level of CD38 expression is MTCN are lacking. Our goal was to study the expression and stability of CD38 on a spectrum of neoplastic T-cell populations and assess the potential anti-tumor effect of anti-CD38 monoclonal antibodies in combination with allogeneic natural killer (NK) cells in MTCN. Methods and results: We searched the Thomas Jefferson University Hospital (TJUH) pathology records for all cases of MTCN for which immune-phenotypical characterization of the neoplastic T-cell population by multi-color flow cytometry (FC) was available. CD38 expression was evaluated in cases where an abnormal T-cell population (defined as loss of one on more pan T-cell markers and/or a skewed CD4 to CD8 ratio). A total of 103 unique patients with MTCN were identified. Of these, 51 had at least one biopsy whereby tumor cells had an abnormal immunophenotype which could then be assessed for CD38 expression. CD38 was expressed to some extent in all but 2 cases with expression levels on peripheral T-cell lymphoma-not other specified (PTCL-NOS)(% Mean±SEM = 80.84±10.26, N=11), angioimmunoblastic T-cell lymphoma (AITL) (% Mean±SEM = 80.56±7.34, N=6), nodal PTCL with T follicular-helper (T FH) phenotype (% Mean±SEM = 55.00±12.72, N=7), anaplastic large cell lymphoma (ALCL) (% Mean±SEM = 77.38±10.75, N=3), large granular lymphocytic leukemia (LGLL) (% Mean±SEM = 80.27±7.49, N=4), T-cell prolymphocytic leukemia (T-PLL) (% Mean±SEM = 88.26±4.20, N=7), cutaneous T-cell lymphoma (CTCL) (% Mean±SEM = 49.52±14.77, N=7), adult T‐cell leukemia/lymphoma (ATLL) (% Mean±SEM = 76.68±10.45, N=3), hepatosplenic T-cell lymphoma/monomorphic epitheliotropic intestinal T-cell lymphoma (HSTCL/MEITL) (% Mean±SEM = 75.00±11.37, N=3). The medians and ranges of the MFI of CD38 on CD38+ tumor cells were the following: PTCL-NOS 29.46 (3.1-115.62), AITL 13.64 (2.67-29.41), other PTCL-T FH 5.87 (0-48.67), ALCL 11.13 (3.6-11.28), LGL (13.52 (9.72-18.25), T-PLL 6.49 (3.09-18), CTCL 8.36 (0-116.75), ATLL 27.17 (3.54-60.5), HSTC