AUTHORS
Yannis K. Valtis I, MD, Karamjeet Singh Sandhu, MD2, Katharine Miller, PhD, MPH3, Amy Zhang, MPH4, Michael R. Grunwald, MD5, Jumana Hoque, MBBS6, Matthew L. Ulrickson, MD7, LaQuisa Hill, MD8, Meera Khosla, MD9, Tamer Othman, MD10, Marlise Rachael Luskin, MD, MSCE11, Evan C. Chen, MD12, Chenyu Lin, MD13, Brian McClune, DO14, Silvina Odstrcil Bobillo15, Stephanie B Tsai, MD16, Timothy O'Connor, MD17, Rawan Faramand, MD18, Jae H Park, MD19, Melhem Solh, MD20, Caitlin Guzowski, MBA21, Jessica Leonard I, M.D.22, Virginia Tan, MD23, Sumithira Vasu, MBBS., MD24, Jiasheng Wang, MD25, Kristen O'Dwyer, MD26, Jozal Moore, MD27, Hrishikesh Srinagesh, MD, MSCR28, Katherine Sutherland, PA29, Caspian Oliai, MD30, Georgia Lill, MD31, Kaitlyn Cecilia Dykes, MD32, Aaron C. Logan, MD, PhD, MPhil33, Ken Byrd, DO34, Michael Daunov, MD35, Veronika Bachanova, MD, PhD36, Sean I. Tracy, MD, PhD37, Matthew P Connor, MD38, Olalekan Oluwole, MD, MPH39, Bhagirathbhai Dholaria, MD, FACP40, Elias Jabbour, MD41, Partow Kebriaei, MD42, Nitin Jain, MD43, Gregory W Roloff, MD44, Bijal Shah, MD, MS45, Ibrahim Aldoss, MD46, Lori Muffly, MD47, Noelle Frey, MD, MSCE48
AFFILIATIONS
1 Memorial Sloan Kettering Cancer Center, New York City, New York, United States
2 City of Hope, Duarte, California, United States
3 Stanford University School of Medicine, Stanford, California, United States
4 Stanford University School of Medicine, Stanford, California, United States
5 Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
6 Banner MD Anderson Cancer Center, Phoenix, Arizona, United States
7 Banner MD Anderson Cancer Center, Phoenix, Arizona, United States
8 Baylor College of Medicine, Houston, Texas, United States
9 Baylor College of Medicine, Houston, Texas, United States
10 City of Hope, Duarte, California, United States
11 Dana Farber Cancer Institute, Boston, Massachusetts, United States
12 Dana Farber Cancer Institute, Boston, Massachusetts, United States
13 Duke Cancer Institute, Durham, North Carolina, United States
14 University of Utah, Salt Lake City, Utah, United States
15 University of Utah, Salt Lake City, Utah, United States
16 Loyola University Medical Center, Maywood, Illinois, United States
17 Loyola University Medical Center, Maywood, Illinois, United States
18 Moffitt Cancer Center, Tampa, Florida, United States
19 Memorial Sloan Kettering Cancer Center, New York City, New York, United States
20 Northside Hospital Cancer Institute, Atlanta, Georgia, United States
21 Northside Hospital Cancer Institute, Atlanta, Georgia, United States
22 Oregon Health & Science University, Portland, Oregon, United States
23 Oregon Health & Science University, Portland, Oregon, United States
24 The Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, United States
25 The Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, United States
26 University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
27 University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
28 Stanford University School of Medicine, Stanford, California, United States
29 Stanford University School of Medicine, Stanford, California, United States
30 UCLA Medical Center, Los Angeles, California, United States
31 UCLA Medical Center, Los Angeles, California, United States
32 UC San Diego School of Medicine, La Jolla, California, United States
33 UC San Francisco School of Medicine, San Francisco, California, United States
34 University of Kansas Medical Center, Leawood, Kansas, United States
35 Case Western Reserve University, University Hospitals Seidman Cancer Center, Cleveland, Ohio, United States
36 University of Minnesota, Minneapolis, Minnesota, United States
37 University of Minnesota, Minneapolis, Minnesota, United States
38 University of Pennsylvania, Philadelphia, Pennsylvania, United States
39 Vanderbilt University, Nashville, Tennessee, United States
40 Vanderbilt University, Nashville, Tennessee, United States
41 The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
42 The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
43 The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
44 University of Chicago School of Medicine, Chicago, Illinois, United States
45 Moffitt Cancer Center, Tampa, Florida, United States
46 City of Hope, Duarte, California, United States
47 Stanford University School of Medicine, Stanford, California, United States
48 University of Pennsylvania, Philadelphia, Pennsylvania, United States
ABSTRACT
Introduction
Obecabtagene autoleucel (obe-cel) is a CD19 targeted chimeric antigen receptor T cell (CAR-T) treatment approved for the treatment of adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). In the registrational trial, the significant majority (72%) of 127 patients (pts) had ≥ 5% bone marrow blasts at the time of lymphodepleting chemotherapy (LDC), while 21% had extramedullary disease (Roddie et al., NEJM 2025). The minority of pts (28%) with low bone marrow burden (<5% blasts) had no Grade 3 or higher (G3+) cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) and showed a promising 12-month event free survival of 68%. Here, we aimed to determine the real-world toxicity and outcomes associated with obe-cel when given in different disease burden settings, by incorporating minimal residual disease (MRD) testing.
Methods
The ROCCA database, comprising data from pts with r/r ALL treated at 25 North American centers was utilized in this analysis. Pts with r/r ALL were included if they received at least one obe-cel infusion since its approval (11/8/2024), had known disease burden at time of lymphodepletion, and had at least 28 days of follow up. Active disease was defined as ≥ 5% bone marrow blasts, or CNS2-3 disease, or non-CNS extramedullary disease (EMD). CR/CRi was defined as < 5% blasts in the bone marrow and no known CNS/EMD. MRD was assessed by flow cytometry, next generation sequencing, and/or quantitative PCR per institutional standards. Event free survival (PFS) was defined as the date from infusion to non-response, relapse (including MRD), or death, censored at last follow up. CRS/ICANS were graded per ASTCT criteria. Infections were graded per BMT CTN. Data cut off was 7/15/2026.
Results
During the study period, 164 pts received an obe-cel infusion and 144 (88%) had adequate disease burden measurement information at LDC to be included in our analysis. Median follow up was 7 months. At LDC, 38 (26%) of pts were in MRD- CR/CRi, 54 (38%) in MRD+ CR/CRi, and 52 (37%) had active disease. Overall, pts in MRD+ or MRD- CR/CRi and those with active disease did not differ substantially with respect to sex, race, and primary language. Regarding performance status, only 2 pts had ECOG status of 3+, all with active disease. A numerically higher proportion of pts with active disease had Philadelphia-like genetics (42%) compared to those with MRD+ CR/CRi (17%) and MRD- CR/CRi (34%).
All pts included in this analysis had the first obe-cel infusion and 142 (99%) received the second infusion. Reasons for non-receipt of second infusion included one patient with high grade CRS and one with progressive disease.
Toxicity differed substantively based on disease burden at LDC. Among pts in MRD- CR/CRi, MRD+ CR/CRi, and active disease, rates of CRS were 40%, 44%, and 73% respectively, while no patient had Gr3+ CRS. Rates of ICANS were 3%, 13%, and 19% respectively, while rates of Gr3+ ICANS were 0, 4%, and 6% respectively. Rates of Gr3+ infections were 9%, 2%, and 25% respectively. Regarding neutrophil recovery, 107 pts had ANC < 500/uL followed by recovery; the median days to recovery were 14, 12, and 29, respectively, for patients in MRD- CR/CRi, MRD+ CR/CRi, and active disease.
Of the 130 pts with known D28 disease response assessment, 99 (76%) were in MRD- CR/CRi at D28. Among pts in MRD- CR/CRi, MRD+ CR/CRi, and active disease at LDC, rates of MRD- CR/CRi at D28 were 94%, 74%, and 64% respectively. Among the three groups, EFS at 12 months was 88%, 74%, and 50% respectively and overall survival at 12 months was 93%, 91%, and 64% respectively. There were 4 non-relapse mortality events, all related to infections.
Conclusion
In contrast with the registrational trial for obe-cel, most pts receiving obe-cel infusions in the real world were in CR/CRi at time of LDC, and many in MRD- CR/CRi. Among those in CR/CRi, toxicity was very favorable with no severe CRS and rare severe ICANS. While longer follow up is needed, preliminary evidence shows very high EFS and OS among those infused in MRD- CR/CRi, pointing to the possible benefit of decreasing disease burden as much as possible prior to infusion.
DISCLOSURES
Yannis K. Valtis I, MD: Valius Science - Current equity holder in private company; Autolus - Research Funding; Autolus - Consultancy (Includes expert testimony); Valius Science - Consultancy (Includes expert testimony)