Satyajit Kosuri
· Assistant Professor of MedicineUniversity of Chicago · Hematology and Blood and Marrow Transplantation
Active 1989–2026
About
Satyajit Kosuri, MD, is an Assistant Professor of Medicine in the Department of Medicine at The University of Chicago. His clinical interests include acute leukemia, myelodysplastic syndromes, myelofibrosis, and various forms of stem cell and cellular therapies such as allogeneic and autologous stem cell transplantation, CAR T cell therapy, and novel immune therapies. Dr. Kosuri's research focuses on outcomes of patients with relapsed or refractory acute leukemia treated with revumenib, as well as the evaluation of therapies for myeloid neoplasms, hereditary hematopoietic malignancies, and the optimization of treatment strategies for older adults undergoing CAR T-cell therapy. His work also encompasses the assessment of prognostic markers in CAR T-cell therapy and the evaluation of treatment outcomes in various hematologic malignancies, contributing to the advancement of personalized and effective treatment approaches in hematology and oncology.
Research topics
- Oncology
- Internal medicine
- Medicine
- Genetics
- Biology
- Pathology
- Immunology
- Surgery
- Cancer research
Selected publications
Transplantation and Cellular Therapy · 2026-02-01
articleTransplantation and Cellular Therapy · 2026-02-01
articleTransplantation and Cellular Therapy · 2026-02-01
articleOpen accessHematopoietic Cell Transplant Access and Patient Diversity
JAMA Network Open · 2026-05-05
articleOpen accessImportance: Allogeneic hematopoietic cell transplant (HCT) is curative for hematologic cancers, yet access remains inequitable for racially and ethnically underrepresented and socioeconomically disadvantaged populations, making the goal of having a suitable donor for every patient who needs a transplant challenging. The ACCESS trial broadened access by enrolling patients without matched donors, who instead received an HCT from a mismatched unrelated donor. Objective: To compare baseline characteristics of ACCESS trial participants with participants enrolled in a similar clinical trial and a patient-reported outcome (PRO) protocol cohort. Design, Setting, and Participants: This cross-sectional study included adult participants (aged ≥18 years) from 3 cohorts-the ACCESS trial (2021-2024), BMT CTN 1703 trial (2019-2021), and Center for International Blood and Marrow Transplant Research (CIBMTR) PRO Protocol observational study (2020-2025)-who completed a baseline PRO survey. The ACCESS and PRO Protocol cohorts were stratified by conditioning intensity (myeloablative [MAC] vs reduced-intensity and nonmyeloablative [RIC/NMA]); all BMT CTN 1703 participants received RIC/NMA. Exposure: Hematopoietic cell transplant. Main Outcomes and Measures: Racial and ethnic diversity, insurance type, education, and income were compared among cohorts using counts and percentages, and socioeconomic and structural disadvantage were measured using the Social Vulnerability Index and Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy. Results: Baseline surveys were completed by 208 participants in the ACCESS trial (median [range] age at transplant, 62.3 [20.4-78.9] years; 108 male [51.9%]), 122 participants in the PRO Protocol study (median [range] age at transplant, 63.9 [21.1-78.0] years; 67 male [54.9%]), and 342 participants in the BMT CTN 1703 trial (median [range] age at transplant, 66.9 [20.7-78.6] years; 218 male [63.7%]). Participants in ACCESS were more racially and ethnically diverse, with 15 (7.2%), 25 (12.1%), 46 (22.2%), 110 (53.1%), and 11 (5.3%) of Asian, Black or African American, Hispanic or Latino, White, and other race and ethnicity, respectively, compared with 4 (3.3%), 2 (1.6%), 8 (6.6%) 104 (85.2%), and 4 (3.3%), respectively, in the PRO Protocol and 10 (3.0%), 0, 16 (4.8%), 302 (91.0%), and 4 (1.2%), respectively, in the BMT CTN 1703 trial. Participants in ACCESS were more likely to have Medicaid (36 [18.1%]) vs PRO Protocol (8 [6.7%]) and BMT CTN 1703 (16 [5.1%]) participants and reported lower education (some college or an associate's degree: 103 [49.5%] vs 73 [59.8%] in the PRO Protocol; postcollege education: 34 [17.3%] vs 35 [29.2%] in the PRO Protocol) and household income (<$40 000 annually: 25 [24.0%] vs 8 [11.6%] in the PRO Protocol and 7 [38.9%] in the BMT CTN 1703 trial). Median Social Vulnerability Index scores were highest among participants in the ACCESS MAC group (median [range], 0.72 [0.01-0.97] vs 0.61 [0.16-0.78] in the PRO Protocol MAC group), and 16 participants [27.6%] in the ACCESS MAC group reported moderate to severe financial toxicity. The ACCESS participants lived closer to transplant centers, especially in the RIC/NMA group (median [IQR], 28 [14-75] miles vs 47 [16-96] miles for BMT CTN 1703 participants and 49 [21-104] miles for PRO Protocol participants). Conclusions and Relevance: This cross-sectional study of clinical trial participants and a clinical cohort found that the ACCESS trial enrolled a more racially and ethnically diverse and socioeconomically disadvantaged population. Trial designs that broaden eligibility could expand access to HCT, highlighting the need for systemic interventions to ensure equity.
2026-03-01
articleOpen accessBritish Journal of Haematology · 2025-10-26 · 1 citations
articleOpen accessRearrangements of the lysine methyltransferase 2A gene (KMT2Ar) and mutations in nucleophosmin 1 (NPM1m) are among the most common genetic aberrations in acute leukaemia, with KMT2Ar seen in both acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) and NPM1m present in ~30% of AML cases.1 Historically, outcomes in relapsed/refractory (R/R) acute leukaemia with KMT2Ar or NPM1m have been poor, with a median overall survival of 6 months or less.2, 3 Both KMT2Ar and NPM1m acute leukaemia harbour leukaemogenic pathways dependent on aberrant transcription and differentiation blocks due to the protein menin. Revumenib, an oral selective menin inhibitor, disrupts leukaemogenesis in both KMT2Ar and NPM1m acute leukaemias.4 The phase 1/2 AUGMENT-101 trial of revumenib in patients with R/R KMT2Ar and NPM1m acute leukaemia demonstrated a complete remission (CR) or complete remission with partial haematological recovery (CRh) rate of 22.8% among patients with KMT2Ar and a CR + CRh rate of 23.4% in those with NPM1m.5, 6 While the single-agent efficacy of revumenib in the R/R setting is promising, the duration of response has been limited; the median overall survival (OS) was 8 months for patients with R/R AML with KMT2Ar and 4 months for those with NPM1m AML.5, 6 Currently, there are limited data regarding outcomes of subsequent therapies in patients already treated with revumenib. We sought to analyse the outcomes of patients with R/R acute leukaemia after receiving revumenib and the efficacy of subsequent treatment lines. Adult patients with R/R acute leukaemia treated with revumenib monotherapy at the University of Chicago between 22 January 2020 and 22 May 2025 were studied as part of a single-centre, retrospective cohort analysis. Patients were identified through the University of Chicago leukaemia registry and pharmacy records. Institutional review board approval was obtained. Diagnosis, relapse and disease status were confirmed according to the International Consensus Classification of myeloid neoplasms and acute leukaemias.7 Risk classification and response assessment for patients with AML utilized the European LeukemiaNet (ELN) 2022 criteria for intensive chemotherapy.8 Response assessments for patients with ALL and mixed-phenotype acute leukaemia (MPAL) utilized the ELN 2024 adult ALL criteria.9 Descriptive statistics were utilized for baseline patient characteristics. A response was defined as achieving a CR, CRh or CR with incomplete count recovery (CRi); overall response rate (ORR) was defined as CR + CRh + CRi. OS was estimated using the Kaplan–Meier method. We evaluated 26 patients treated with revumenib monotherapy for R/R acute leukaemia in our analysis. Twenty patients (76.9%) received revumenib as part of a clinical trial, 4 (15.4%) as part of an expanded access protocol and 2 (7.7%) as a commercial drug. Most patients (73%) had AML; the remainder had B-ALL (15%) or rare subtypes (12%). Demographic and biological characteristics are presented in Table 1. Fifteen patients (58%) received revumenib for KMT2Ar, 10 (38%) for an NPM1m and 1 (4%) for a KMT2A partial tandem duplication (PTD) (Figure S1A,B). The patient with KMT2A-PTD previously received all available standard therapies and was therefore treated with revumenib given preclinical rationale for menin inhibition.10 Twenty patients had a comprehensive molecular evaluation at initial diagnosis. Aside from KMT2Ar and NPM1m, common pathogenic mutations at diagnosis included fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (5/20, 25%), neuroblastoma RAS viral oncogene homolog (NRAS) (5/20, 25%), Kirsten rat sarcoma viral oncogene homolog (KRAS) (4/20, 20%), tet methylcytosine dioxygenase 2 (TET2) (4/20, 20%) and tumor Protein P53 (TP53) (2/20, 10%) (Figure S1A). Responses to revumenib are summarized in Table 1; the ORR rate was 42% (11/26). Fifteen patients received additional treatment after revumenib (post-revumenib treatment). Of the 11 patients who did not receive post-revumenib treatment, 10 (91%) died either while taking revumenib, after cessation due to no response, or due to other complications of their leukaemia, while 1 (9%) remained on revumenib at the time of data cut-off (Figure 1B). The median OS of the 26-patient cohort from the time of revumenib initiation was 7.3 months (95% confidence interval (CI) [2.5, 14.4]). Fourteen patients had repeat molecular assessments via next-generation sequencing (NGS) at the time of no response or progression on revumenib (Figure S1C), of which 5 (36%) developed a multiple endocrine neoplasia 1 (MEN1) mutation, a known driver of resistance to revumenib.11 Of the 5 patients who developed MEN1 mutations, 3 (60%) had NPM1m and 2 (40%) had KMT2Ar. Of the 15 patients who received post-revumenib treatment, 5 (33%) had an NPM1 mutation, 9 (60%) had KMT2Ar and 1 (7%) had a KMT2A-PTD. Twelve patients (80%) received one or two lines of treatment following revumenib, and three patients (20%) received ≥3 lines of treatment (Table S1). As the first line of post-revumenib treatment, 6 (40%) received a hypomethylating agent (HMA) + venetoclax (ven), 5 (33%) received intensive chemotherapy (IC) + ven, 2 (13%) with FLT3 mutations received gilteritinib-based therapy, 1 (7%) with B-ALL received CD19-directed chimeric antigen receptor T-cell (CAR T) therapy and 1 (7%) received revumenib again after previously achieving a CR on revumenib, undergoing allogeneic haematopoietic stem cell transplant (allo-HSCT), and having another relapse of disease. Of the 26 patients, 18 (69%) received ven prior to revumenib. Of these, five (28%) achieved a response to revumenib. Nine patients (50%) went on to receive post-revumenib therapy. Seven of the nine patients (78%) were retreated with ven-containing regimens post-revumenib. Two of seven patients (29%) achieved a response to a ven-containing regimen post-revumenib. Following the first line of post-revumenib treatment, 8 patients (53%) had no response. Of these, 5 (62.5%) had KMT2Ar, 2 (25%) had NPM1 mutations and 1 (12.5%) had a KMT2A-PTD. Three patients achieved a CR while four achieved a CRi for an ORR of 47% (Table S1). Among these 7 patients who achieved a response, 3 (42.8%) received HMA + ven, 2 (28.8%) received IC + ven, 1 (14%) received gilteritinib-based therapy and 1 (14%) received CAR-T therapy. Among the seven patients with a response after the first line of therapy post-revumenib, three (43%) had KMT2Ar and four (57%) had an NPM1 mutation. Among the four patients with an NPM1 mutation who achieved a response after their first line of post-revumenib therapy, NPM1 measurable residual disease (MRD) status was assessed via NGS assay with 10−5 sensitivity. Two patients (50%) were MRD positive at assessment post-revumenib, and 2 (50%) achieved and maintained MRD-negative status. Of the two patients with MRD-positive disease, one patient switched to HMA therapy and has not had subsequent NPM1 MRD assessments at the time of data cut-off, and the other patient died prior to repeat MRD assessment. Four patients who received post-revumenib therapy had a MEN1 mutation. Two of these patients had NPM1m disease and received HMA + ven; both patients achieved a response. Two patients had KMT2Ar and received HMA + ven but did not have a response. Among the 15 patients who received post-revumenib treatment, the median OS was 7.5 months (95% CI [2.3, NA]) from the time of first post-revumenib treatment and was 8.3 months (95% CI [7.8, NA]) in the seven patients who achieved a CR/CRi to their first post-revumenib treatment (Figure 1A). Of the 15 patients, 7 (47%) received additional treatment lines beyond the first line of post-revumenib therapy; their courses are summarized in the swimmer plots (Figure 1A). Of the post-revumenib treatment cohort, four patients (27%) were still alive at the time of data cut-off (Figure 1A). Of the 15 patients who received post-revumenib therapy, 6 (40%) subsequently underwent allo-HSCT; three patients died from relapsed disease and three are still alive at the time of data cut-off. The median OS from the time of allo-HSCT was 8.8 months (95% CI [4.8, NA]). In summary, this analysis characterized the clinical outcomes of 26 patients with R/R acute leukaemia treated with revumenib. The ORR was 47% in the 15 patients who received post-revumenib therapy, with most patients receiving ven-containing regimens (n = 11) as the next line of treatment. Responses were seen in patients with KMT2A aberrations (3/10), NPM1 mutations (4/5) and MEN1 mutations (2/4), suggesting that additional therapy may be effective across the common aberrations seen after relapse/progression on revumenib. Of the 15 patients who received post-revumenib therapy, 6 were able to proceed to an allo-HSCT. Prior work has demonstrated that responses to menin inhibitors in the R/R setting are typically limited in duration and that if MRD-negative status can be achieved, patients benefit from proceeding to transplant promptly.5, 6, 12 Limitations of our analysis include the small sample size. Many patients received revumenib through a clinical trial or through an expanded access programme. Therefore, our findings may not reflect the broader population which has more limited access to such resources. Nevertheless, our study provides insight into potential therapeutic strategies for revumenib-exposed patients. To our knowledge, this is the first report describing outcomes of subsequent therapies after revumenib exposure in a real-world cohort. We found that post-revumenib therapies, particularly venetoclax-based approaches, can induce responses across mutational subsets including MEN1. In addition, consolidation with allo-HSCT is feasible in eligible patients who achieve a response. Prospective studies evaluating therapies, including other menin inhibitors, in patients already treated with revumenib will be critical to understand how to improve outcomes in this group.13 As menin inhibitors are investigated in the front-line setting, similar studies might inform combinatorial trial designs and identify effective treatments after menin inhibitor therapy.14, 15 Miles Thomas was responsible for project design, data collection, data analysis and manuscript creation. Hannah Johnston was responsible for project design, data collection, data analysis and manuscript creation. Emily Dworkin was responsible for manuscript creation. Austin Wesevich was responsible for manuscript creation. Gregory W. Roloff was responsible for manuscript creation. Caner Saygin was responsible for manuscript creation. Mariam T. Nawas was responsible for manuscript creation. Michael W. Drazer was responsible for manuscript creation. Adam S. DuVall was responsible for manuscript creation. Satyajit Kosuri was responsible for manuscript creation. Michael J. Thirman was responsible for manuscript creation. Olatoyosi Odenike was responsible for manuscript creation. Wendy Stock was responsible for manuscript creation. Richard A. Larson was responsible for manuscript creation. Rafael Madero-Marroquin was responsible for project concept and design, data collection, data analysis and manuscript creation. Anand A. Patel was responsible for project concept and design, data collection, data analysis and manuscript creation. The authors would like to thank the patients whose data are represented in the study below. Anand A. Patel is supported by the NCI Early Career Investigator Award (3P30CA014599-49S1). Miles Thomas: No conflicts of interest to disclose. Hannah Johnston: No conflicts of interest to disclose. Emily Dworkin: Honoraria from AbbVie. Austin Wesevich: Honorarium from Amgen. Gregory W. Roloff: Advisory boards for Autolus Therapeutics and Kite/Gilead. Caner Saygin: No conflicts of interest to disclose. Mariam T. Nawas: No conflicts of interest to disclose. Michael W. Drazer: Scientific advisory board for Argenx. Adam S. DuVall: Speaker for CE Concepts. Satyajit Kosuri: No conflict of interest to disclose. Michael J. Thirman: Has acted as a consultant or advisor to AbbVie, AstraZeneca, Celgene, Janssen, Pharmacyclics and Roche/Genentech. Research funding from AbbVie (Inst), Gilead Sciences, Janssen, Merck, Nurix, Pharmacyclics, Syndax and TG Therapeutics. Olatoyosi Odenike: Institutional research funding by AbbVie, Astra Zeneca, Celgene, Curis, Incyte, Shattuck Lab and K-group alpha; scientific advisory board participant for AbbVie, Celgene/BMS, Novartis, Incyte, Kymera therapeutics, Servier and Rigel; service on data safety board for Treadwell therapeutics. Wendy Stock: Advisor for Kura, Servier, Newave and Asofarma. Richard A. Larson has acted as a consultant or advisor to Ariad/Takeda, CVS/Caremark, Epizyme/Ipssen and Novartis and has received clinical research support to his institution from Astellas, Biomea, Cellectis, Daiichi Sankyo, Forty Seven/Gilead and Novartis and royalties from UpToDate. Rafael Madero-Marroquin: No conflicts of interest to disclose. Anand A. Patel: Honoraria from AbbVie, Amgen, Astellas, Jazz, Sobi, Syndax; research funding (institutional) from Pfizer, Incyte, Servier and Sumitomo. Informed consent was waived as per institutional review board approval due to the retrospective nature of the study. Those seeking to reproduce material from this manuscript should reach out to the corresponding author for permission. The data used for this study can be made available in its de-identified form at the request of the corresponding author upon reasonable request and following institutional data sharing practices. To protect the confidentiality and security of individual health records, these data will not be made publicly available. Figure S1. Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Another Feather in the Cap for Posttransplant Cyclophosphamide GVHD Prophylaxis?
JAMA Oncology · 2025-11-06
article1st authorCorrespondingBlood · 2025-11-03
articleOpen accessAbstract Background and significance: T-lineage acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for 15% of pediatric and 25% of adult ALL cases. Precursor T-ALL and its more immature subset, early T precursor (ETP) ALL, have limited treatment options after first-line chemotherapy. Due to this unmet need, long-term survival for relapsed/refractory (R/R) T-ALL is &lt;10%. During normal T-cell development in thymus, early precursor cells first rearrange T-cell receptor β chain (TCRβ), which pairs with an invariant surrogate pre-Tα chain to create pre-TCR signaling complex. Pre-TCR signaling promotes cell survival, proliferation and differentiation in a ligand-independent manner. We and others have shown that in T-ALL, oncogenic mutations frequently hijack this pathway, leading to constitutive activation of downstream signaling cascades. We discovered that the inhibition of pre-TCR (LCK) signaling leads to induction of apoptosis in T-ALL, and BCL-2/BCL-xL inhibitors which activate suicide pathways can synergize with LCK inhibitors (Saygin, Clin Cancer Res 2023). LP-118 is an oral dual BCL-2/BCL-xL inhibitor, with a modified structure and fine-tuned BCL-xL activity to minimize platelet toxicity. Based on our preclinical work showing the synergy between LP-118 and ponatinib (pre-TCR signaling inhibitor), we designed the phase 1/2 LPVd trial combining LP-118 and ponatinib (LCK inhibitor) with low-intensity chemotherapy backbone (Vd: vincristine, dexamethasone) in patients with R/R T-ALL/LBL (NCT06207123). The trial was activated at the University of Chicago in September 2024, and we plan to open it at four additional sites. Study design and methods: Adult patients (≥18 years) with R/R T-ALL/LBL, defined as bone marrow or blood involvement with ≥5% lymphoblasts, or measurable residual disease (MRD) with &gt;10-4 level detected by multiparameter flow cytometry or NGS-based MRD, or patients with isolated extramedullary disease that is measurable by CT scan are eligible. Participants should otherwise have good performance status (ECOG 0-2), adequate organ function, and no active infections. In phase 1, a standard 3+3 design is implemented to test the combination of different dose levels of LP-118 with low-intensity chemotherapy (Vd) at dose levels 1 (100 mg), 2 (200 mg) and 3 (300 mg), followed by the addition of ponatinib 30 mg to different dose levels of LP-118 at levels 4 (100 mg), 5 (200 mg) and 6 (300 mg). Ponatinib dose reduction to 15 mg is allowed for participants who experience toxicity or achieve MRD-negative remission. The primary objective of the phase 1 portion is to identify the recommended phase 2 dose (RP2D) of this novel-novel combination therapy. The primary endpoint is dose limiting toxicity (DLT), defined as a grade ≥3 non-hematologic toxicity related to the study drugs, except for the following which will not be considered DLT: grade 3 fatigue, asthenia, fever, anorexia, constipation; grade 3 nausea, vomiting or diarrhea not requiring tube feeding, total parenteral nutrition or hospitalization; infection, bleeding or other expected direct complication of cytopenias due to active underlying leukemia. The maximum tolerated dose is the dose such that &lt;33% of patients (&lt;2 of 6) experience DLT. At the time of this submission, 9 patients have been enrolled. After identifying the RP2D from the phase 1 portion, we will do a phase 2 dose expansion by enrolling 12 additional patients at this dose level to investigate the efficacy of LPVd. R/R T-ALL is a rare disease for which large phase III studies are rarely conducted. Primary endpoint of the phase 2 portion is complete remission (CR). The CR rate with re-induction chemotherapy in patients with R/R T-ALL is 10%. A previous phase 1b/2 study of venetoclax, navitoclax and chemotherapy in R/R T-ALL showed 50% CR rate. Therefore, we anticipate a CR rate of 30% in our study, which combines LP-118 with similar chemotherapy backbone. A total of 18 patients are needed to achieve 80% power under one-sided alpha= 0.10. We will include 6 patients from phase 1 portion in our efficacy analysis. Several correlative studies are planned to identify biomarkers of response and resistance, including BH3 profiling, molecular genetic profiling (DNA- and RNA-seq), and pre-TCR signaling activity in baseline vs relapse samples. This investigator-initiated trial is funded by the Leukemia Lymphoma Society Academic Clinical Trials grant.
Blood · 2025-11-03
articleAbstract Introduction: Autologous CD19 CART therapies have been utilized across a wide range of B cell driven autoimmune diseases (AD), including systemic lupus erythematous (SLE), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SSc), & myasthenia gravis (MG). To date, a number of autologous CD19-CART therapies have delivered durable drug free responses in AD patients. However, the safety profile of autologous CD19-CART therapies across different AD has yet to be fully explored. This is especially true for CRS & ICANS. Here, we provide novel insight into the mechanism underlying the safety profile of resecabtagene autoleucel (rese-cel) an autologous CD19 41BBz CART therapy across four separate Phase I/II clinical trials in SLE, IIM, SSc, & MG. Objectives: The primary objective of each trial is safety & tolerability of rese-cel at Day 29. Key secondary objectives include changes in clinical scores & use of immunomodulatory agents. Key translational assessments include CART cell pharmacokinetics (PK), impact on peripheral B cell populations (pharmacodynamics), & serum cytokine levels. Methods: 19 Patients (data cutoff: 6/2/2025 SLE; 5/6/2025 IIM, SSc, and MG), with active disease refractory to standard of care have been treated across 4 Phase I/II clinical trials in SLE (8 patients; NCT06121297), IIM (8 patients; NCT06154252), SSc (2 patients; NCT06328777), & MG (1 patient; NCT06359041). All patients were treated with a single weight-based infusion of rese-cel at a dose of 1 x 106 cells/kg following lymphodepletion (flu 25 mg/m2/d on Days -5, -4, & -3, & cy 1,000 mg/m2/d on Day -3). All non-glucocorticoid immunomodulatory agents were stopped prior to lymphodepletion. Glucocorticoids were tapered post-infusion. Patients were not given prophylactic tocilizumab pre-infusion. Translational assessments were determined as follows: CART PK was evaluated by flow cytometry & dPCR; B-cell enumeration & phenotyping were evaluated by flow cytometry; & serum cytokines were evaluated via immunoassay. Results: Across all indications (19 patients), 7 episodes of CRS were observed (7/19). 6 of 7 patients experienced a Grade 1 CRS, & 1 patient had a Grade 2 CRS. 2 patients developed ICANS; 1 patient had a Grade 4 (previously presented at ACR Convergence 2024), & the other patient had a Grade 3. Both ICANS events were rapidly resolved without sequelae using standard therapy. These CRS and ICANS events differed across indications. In IIM, 4 of 8 patients experienced Grade 1 CRS and no patients experienced ICANs. In SLE, 2 patients experienced Grade 1 CRS and one developed Grade 4 ICANs. In SSC, 1 of 2 patients experienced Grade 2 CRS & the other experienced Grade 3 ICANS. In MG, no CRS or ICANS was observed. Rese-cel infusion products were ~ 66% transduced, with a mean CD4:CD8 ratio of 6. Post-infusion, peak CART expansion was observed on day 12 & the mean peak expansion was 89 cells/µL (SD +/- 214). B cells were rapidly depleted from peripheral blood post-infusion, with nadir occurring at 13 days & repopulation beginning at 62 days post-infusion on average. Re-emergent B cells were largely of the CD24+CD38+ transitional naïve phenotype. Commensurate with B cell depletion, serum BAFF induction was observed, with a mean fold induction of 16 & mean peak level of 56,404 pg/µL (SD: +/- 45,547). Serum cytokines associated with CRS & ICANS; IFNg, IL6, & IL8 reached peak elevation on days 10, 9, & 10 respectively post-infusion. The mean peak elevation for IFNg, IL6, & IL8 were 232 pg/ µL (SD: +/- 320), 44 pg/ µL (SD: +/- 60), & 80 pg/ µL (SD +/- 73), respectively. Conclusion: Rese-cel appears to be well tolerated in autoimmune patients with rates of CRS & ICANS of 37% & 11% across all autoimmune indications, respectively (SLE patients had a 25% CRS rate & 12.5% ICANS rate, IIM patients had a 50% CRS rate & 0% ICANS rate, SSC patients had a 50% CRS & 50% ICANS rate, & MG patients had a 0% CRS & ICANS rate). Notably, the frequency & severity of CRS appears to be low, with no CRS in 63% of patients (12/19) & most CRS events (6/7) being Grade 1. The lower frequency & severity of both CRS & ICANS events are likely correlated with the relatively modest induction of serum IFNg, IL6, & IL8 found in autoimmune patients post rese-cel weight-adjusted dose infusion. High BAFF levels reflect deep systemic B cell depletion. Together, these data support further support late-stage clinical development of rese-cel in autoimmune disease.
eJHaem · 2025-06-01 · 1 citations
articleOpen accessBackground: Outcomes for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that have progression after treatment with hypomethylating agent (HMA) and venetoclax (VEN) are poor. However, data for chemotherapy and VEN (C+VEN) therapy after prior treatment with HMA+VEN are limited. Methods: We identified 18 patients with AML or MDS/AML who received C+VEN after prior HMA+VEN. Results: Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 7 patients (39%) and 6 patients (33%) proceeded to allogeneic hematopoietic stem cell transplantation. Conclusion: This study shows suggests that C+VEN could be a viable option in a subset of patients after HMA+VEN.
Frequent coauthors
- 46 shared
Sergio Giralt
Memorial Sloan Kettering Cancer Center
- 43 shared
Michael R. Bishop
University of Illinois Chicago
- 35 shared
Peter A. Riedell
University of Chicago
- 34 shared
Guenther Koehne
Miami Heart Research Institute
- 31 shared
Miguel-Ángel Perales
- 30 shared
Andrew Artz
City of Hope
- 28 shared
Hongtao Liu
Shanghai Zhangjiang Laboratory
- 28 shared
Wendy Stock
University of Chicago
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