Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia

Karen L. Bride, Tiffaney L. Vincent, Soo-Yeon Im, Richard Aplenc, David M. Barrett, William L. Carroll, Robin Carson, Yunfeng Dai, Meenakshi Devidas, Kimberly P. Dunsmore, Tori Fuller, Tina Glisovic-Aplenc, Terzah M. Horton, Stephen P. Hunger, Mignon L. Loh, Shannon L. Maude, Elizabeth A. Raetz, Stuart S. Winter, Stephan A. Grupp, Michelle L. Hermiston, Brent L. Wood and David T. Teachey

Key Points

  • Daratumumab is effective against T-ALL in human xenograft models.

  • CD38 is a novel target with broad potential in the treatment of T-ALL.

Publisher's Note: There is a Blood Commentary on this article in this issue.


As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-cell ALL; however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL. We demonstrate that blasts from patients with T-ALL have robust surface CD38 surface expression and that this expression remains stable after exposure to multiagent chemotherapy. CD38 is expressed at very low levels on normal lymphoid and myeloid cells and on a few tissues of nonhematopoietic origin, suggesting that CD38 may be an ideal target. Daratumumab is a human immunoglobulin G1κ monoclonal antibody that binds CD38, and has been demonstrated to be safe and effective in patients with refractory multiple myeloma. We tested daratumumab in a large panel of T-ALL patient-derived xenografts (PDX) and found striking efficacy in 14 of 15 different PDX. These data suggest that daratumumab is a promising novel therapy for pediatric T-ALL patients.

  • Submitted July 7, 2017.
  • Accepted December 11, 2017.
View Full Text