Outcomes for adult pts with R/R ALL are poor. Promising results were observed with axi-cel (KTE-C19), an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in B cell malignancies (Locke et al. AACR 2017, #9986). Severe cytokine release syndrome (CRS) and neurologic events (NE) have been observed in pts with R/R ALL who received anti-CD19 CAR T cell therapy.
Eligible pts were aged ≥18 years with R/R ALL (Ph+ pts eligible), >5% bone marrow (BM) lymphoblasts, ECOG status 0-1, and adequate organ function. Pts received 1 or 2 × 106 CAR T cells/kg after conditioning (cyclophosphamide + fludarabine). Phase 1 primary endpoint was incidence of dose-limiting toxicity (DLT). Secondary endpoints were efficacy outcomes.
As of 12/31/2016, 12 pts were enrolled; 11 received KTE-C19. One pt was excluded due to a serious adverse event (SAE) prior to dosing. Pts were 64% men, had 56-100% BM lymphoblasts before conditioning and 64% vs 36% had relapsed vs primary refractory disease. No DLTs were observed in the DLT-evaluation period of this trial. Of the first 6 pts enrolled at the 2 × 106 dose, 1 experienced Gr5 CRS. No KTE-C19-related Gr5 AEs were observed at 1 × 106 dose in 5 subsequent pts. Overall, the most common Gr ≥ 3 AEs were cytopenias (64% thrombocytopenia, 55% neutropenia). Gr ≥ 3 CRS and NE were reported in 27% and 55% of pts. Tocilizumab (toci) or steroids was given for AE management in 10 and 7 pts, respectively. All CRS (except 1 Gr 5) and NE resolved. Of the 10 efficacy-evaluable pts, 9 (90%) achieved minimal residual disease-negative remission (8 CR or CR with partial/incomplete hematopoietic recovery; 1 blast-free hypoplastic/aplastic BM). Median follow-up was 3.8 mos; 3 pts relapsed: 2 CD19- and 1 CD19+ disease. Efficacy was similar across KTE-C19 doses. To refine dosing and AE management, additional pts were treated with lower CAR T cell doses and received prophylactic toci. Clinical outcomes and translational data from these pts will be presented.
KTE-C19 demonstrates promising efficacy with a manageable safety profile for adult R/R ALL pts. Novel approaches to reducing toxicity, namely CRS and NE, may improve the overall risk: benefit profile for this class of therapies.
Clinical trial identification
Legal entity responsible for the study
B. Shah: Celgene: Advisory Board, Speaker Fees, Honorarium Bayer: Honorarium Spectrum: Speaker Fees Pharmacyclics: Speaker Fees Plexus Communications: Honorarium Rosetta Genomics: Grant Support Acetilon: Advisory Board Pfizer: Advisory Board Baxalta: Honorarium. W. Stock: Honoraria: Amgen, Pfizer, Seattle Genetics. W. Wierda: Research Funding: Kite, Juno; Travel/Accomodations/Expenses: Kite, Juno. M. Topp: Honoraria: Amgen Consulting or Advisory: Amgen, Regeneron, Roche Travel, Accomodation, Expenses: Amgen, Roche Speakers Bureau: Amgen Research Funding: Amgen, Regeneron, Roche Expert Testimony: Amgen, Regeneron. G.J. Schiller: Research Funding: Novartis, Karyopharm, Amgen, Sunesis, Astellas, Spectrum, Bluebird, Celgene, Array Pharmaceutical Honorarium: Amgen, Sunesis, Celgene Speakers Bureau: Amgen, Celgene. A. Mardiros: Patents: Mustang Bio. J. Rossi, Y. Jiang, T. Shen, J. Aycock, S. Stout: Employment: Kite Pharma. J. Wiezorek: Leadership: Kite. R. Jain: Patent: Kite Pharma. All other authors have declared no conflicts of interest.