1007PD - Preliminary Results of Novel Safety Interventions in Adult Patients (Pts) With Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) in the ZU...

Date 11 September 2017
Event ESMO 2017 Congress
Session Haematological malignancies
Topics Cancers in Adolescents and Young Adults (AYA)
Haematologic Malignancies
Presenter Bijal Shah
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors B. Shah1, W. Stock2, W. Wierda3, M. Topp4, M.J. Kersten5, R. Houot6, N. Boissel7, H.E. Holmes8, G.J. Schiller9, A. Mardiros10, J. Rossi10, Y. Jiang11, T. Shen10, J. Aycock10, S. Stout10, J. Wiezorek10, R. Jain10
  • 1Malignant Hematology, H. Lee Moffitt Cancer Center University of South Florida, 33612 - Tampa/US
  • 2Comprehensive Cancer Center, The University of Chicago, 60637 - Chicago/US
  • 3Department Of Leukemia, Division Of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 4Haematology, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, 97070 - Wurzburg/DE
  • 5Internal Medicine, Clinical Haematology, AMC-UvA (Academic Medical Center- University of Amsterdam), 1105 - Amsterdam/NL
  • 6Department Of Hematology, CHU de Rennes, 35033 - Rennes/FR
  • 7Hematology, Saint-Louis Hospital, APHP, 75010 - Paris/FR
  • 8Texas Oncology-baylor Charles A. Sammons Cancer Center, Texas Oncology, 75251 - Dallas/US
  • 9Medicine, Hematology & Oncology, UCLA School of Medicine, 90095 - Los Angeles/US
  • 10Clinical Development, Kite pharma, 90404 - Santa Monica/US
  • 11Clinical Development, Kite Pharma, 90404 - Santa Monica/US



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

Kite Pharma


Kite Pharma


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.