Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

Frigault, Matthew J; Graham, Charlotte E; Berger, Trisha R; Ritchey, Julie; Horick, Nora K; El-Jawahri, Areej; Scarfò, Irene; Schmidts, Andrea; Haradhvala, Nicholas J; Wehrli, Marc; Lee, Won-Ho; Parker, Aiyana L; Wiggin, Hadley R; Bouffard, Amanda; Dey, Aonkon; Leick, Mark B; Katsis, Katelin; Elder, Eva L; Dolaher, Maria A; Cook, Daniella T; Chekmasova, Alena A; Huang, Lu; Nikiforow, Sarah; Daley, Heather; Ritz, Jerome; Armant, Myriam; Preffer, Fred; DiPersio, John F; Nardi, Valentina; Chen, Yi-Bin; Gallagher, Kathleen M E; Maus, Marcela V     «

Frigault, Matthew J; Graham, Charlotte E; Berger, Trisha R; Ritchey, Julie; Horick, Nora K; El-Jawahri, Areej; Scarfò, Irene; Schmidts, Andrea; Haradhvala, Nicholas J; Wehrli, Marc; Lee, Won-Ho; Parker, Aiyana L; Wiggin, Hadley R; Bouffard, Amanda; Dey, Aonkon; Leick, Mark B; Katsis, Katelin; Elder, Eva L; Dolaher, Maria A; Cook, Daniella T; Chekmasova, Alena A; Huang, Lu; Nikiforow, Sarah; Daley, Heather; Ritz, Jerome; Armant, Myriam; Preffer, Fred; DiPersio, John F; Nardi, Valentina; Chen, Yi-...     »

We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients. Tumor responses were observed in 4 of 5 patients with 3 complete responses, 1 mixed response, and 1 patient whose disease progressed rapidly and with relative loss of CD37 expression. Three patients experienced prolonged and severe pancytopenia, and in 2 of these patients, efforts to ablate CAR-37 T cells, which were engineered to coexpress truncated epidermal growth factor receptor, with cetuximab were unsuccessful. Hematopoiesis was restored in these 2 patients after allogeneic hematopoietic stem cell transplantation. No other severe, nonhematopoietic toxicities occurred. We investigated the mechanisms of profound pancytopenia and did not observe activation of CAR-37 T cells in response to hematopoietic stem cells in vitro or hematotoxicity in humanized models. Patients with pancytopenia had sustained high levels of interleukin-18 (IL-18) with low levels of IL-18 binding protein in their peripheral blood. IL-18 levels were significantly higher in CAR-37-treated patients than in both cytopenic and noncytopenic cohorts of CAR-19-treated patients. In conclusion, CAR-37 T cells exhibited antitumor activity, with significant CAR expansion and cytokine production. CAR-37 T cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant. This trial was registered at www.ClinicalTrials.gov as #NCT04136275.      «

We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients. Tumor responses were observed in 4 of 5 patients with 3 complete respon...     »