33 results on '"D. Jeyakumar"'
Search Results
2. S166: MAGROLIMAB IN COMBINATION WITH AZACITIDINE FOR PATIENTS WITH UNTREATED HIGHER-RISK MYELODYSPLASTIC SYNDROMES (HR MDS): 5F9005 PHASE 1B STUDY RESULTS
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D. A. Sallman, M. M. Al Malki, A. S. Asch, E. S. Wang, J. G. Jurcic, T. J. Bradley, I. W. Flinn, D. A. Pollyea, S. N. Kambhampati, T. N. Tanaka, J. F. Zeidner, G. Garcia-Manero, D. Jeyakumar, L. Gu, A. Tan, M. Chao, C. O’Hear, I. Lal, P. Vyas, and N. Daver
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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3. P356: SUBGROUP ANALYSES OF KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R B-ALL) IN ZUMA-3
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B. D. Shah, R. D. Cassaday, J. H. Park, R. Houot, O. O. Oluwole, A. C. Logan, N. Boissel, T. Leguay, M. R. Bishop, M. S. Topp, D. Tzachanis, K. M. O’Dwyer, M. L. Arellano, Y. Lin, M. R. Baer, G. J. Schiller, M. Subklewe, M. Abedi, M. C. Minnema, W. G. Wierda, D. J. DeAngelo, P. Stiff, D. Jeyakumar, J. Dong, S. Adhikary, L. Zhou, P. C. Schuberth, B. Kharabi Masouleh, and A. Ghobadi
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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4. P555: A PHASE 1B/2 STUDY OF THE CD123-TARGETING ANTIBODY-DRUG CONJUGATE PIVEKIMAB SUNIRINE (IMGN632) IN COMBINATION WITH VENETOCLAX (VEN) AND AZACITIDINE (AZA) FOR PATIENTS WITH CD123-POSITIVE AML
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N. G. Daver, P. Montesinos, A. Aribi, G. Martinelli, J. Altman, G. Roboz, E. S. Wang, P. W. Burke, D. Jeyakumar, R. B. Walter, D. J. DeAngelo, H. P. Erba, A. Advani, L. Gastaud, X. Thomas, E. Todisco, N. Pemmaraju, L. Mendez, A. de la Fuente, G. Gaidano, A. Curti, N. Boissel, C. Recher, C. Schliemann, P. Vyas, C. M. Sloss, J. Wang, K. A. Malcolm, P. A. Zweidler-McKay, and K. L. Sweet
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. Enhanced Reliability in Network Function Virtualization by Hybrid Hexagon-Cost Efficient Algorithm.
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D. Jeyakumar and C. Rajabhushanam
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- 2022
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6. Assessment on Performance and Emission Characteristics of the CRDI Engine Fueled with Ethanol/Diesel Blends in Addition to EGR
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C. Dineshkumar, P. D. Jeyakumar, C. K. Arvinda Pandian, N. Rajmohan, P. V. Elumalai, N. Kamesh, Saboor Shaik, Mohsen Sharifpur, and Nima Khalilpoor
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Chemical engineering ,TP155-156 - Abstract
In this research, the CRDI engine characteristics were analyzed with the aid of exhaust gas recirculation rate (EGR) adoption fueled with ethanol blends. The test fuels were the various blends with ethanol, such as (10% of ethanol + 90% of diesel) E10D90 (20% of ethanol + 80% of diesel), E20D80, and (30% of ethanol + 70% of diesel) E30D70. From the results, it was revealed that performance characteristics were reduced when using a higher concentration of the alcohols mixed with diesel fuel. The blend E30D70 showed that brake thermal efficiency (BTE) without EGR drops by 3.8%, increased by 9.14% of BSFC, a 9.25% decrease in oxides of nitrogen emissions, and slightly decreased CO and HC emissions compared to baseline diesel operation at 60% load condition. The blend E10D90 with 20% EGR shows the highest BTE of 8.87% when compared with base fuel, due to proper fuel mixture taking place in the inlet manifold. The results indicate that the engine runs smoothly, and E30D70 has chosen an optimum blend. A further experiment was performed using E30D70 with different rates of exhaust gas recirculation system. The addition of exhaust gas recirculation with E30D70 in the common rail diesel engine exhibits oxides of nitrogen emission, but in contrast, it was noticed to have inferior performance characteristics and drastically decreased HC and CO emissions. The hydrocarbon emission decreased E10D90, E20D80, and E30D70 at 60% load condition by 21.42%, 37.38%, and 48.76%, respectively. The blends E10D90, E20D80, and E30D70 decreased carbon dioxide by 7.9%, 30.08%, and 31.98%, respectively. The maximum reduction of NOx emission was observed at about 51.06% at an EGR rate of 20% with E30D70.
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- 2022
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7. Correction: Effects of novel intake manifold design and investigation of diesel engine operating on different alternative fuels
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P. Arjunraj, P. D. Jeyakumar, C. Dineshkumar, and M. Bharathiraja
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Physical and Theoretical Chemistry ,Condensed Matter Physics - Published
- 2022
8. Sign Language Interpreter
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Brindha, R., primary, Renukadevi, P., additional, Vathana, D., additional, and D, Jeyakumar, additional
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- 2022
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9. The Performance Analysis of a Location based Weather Identification Device
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S.Pradeep Kumar, P. Renukadevi, M.Raja Suguna, and D. Jeyakumar
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- 2022
10. OUTFS+. An Efficient User-Side Encrypted File System Using IBE With Parallel Encryption
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D Jeyakumar, K. Chidambarathanu, S. Pradeepkumar, and T.P. Anish
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- 2022
11. Band guard- a dynamic security tool for women protection using data analysis
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P. Renukadevi, R. Brindha, D. Jeyakumar, and N. Kanagavalli
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- 2022
12. Agriculture Crop Selection and Yield Prediction using Machine Learning Algorithms
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M Aruna Devi, Dhina Suresh, D Jeyakumar, D Swamydoss, and M Lilly Florence
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- 2022
13. Design of Hyperparameter Tuned Deep Learning based Automated Fake News Detection in Social Networking Data
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Kanagavalli, N., primary, Priya, S. Baghavathi, additional, and D, Jeyakumar, additional
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- 2022
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14. INFLUENCE OF TEMPERATURE, IMPINGEMENT ANGLE, VELOCITY AND STANDOFF DISTANCE ON THE EROSION CHARACTERISTICS OF INCONEL 718 AND Ti-6Al-4V
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G. Rajamurugan, P. D. Jeyakumar, Gautam D. Bhushan, and Prabu Krishnasamy
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Gas turbines ,Jet (fluid) ,Metallurgy ,Materials Chemistry ,Erosion ,Environmental science ,Surfaces and Interfaces ,Ti 6al 4v ,Condensed Matter Physics ,Inconel ,Surfaces, Coatings and Films - Abstract
Erosion is the primary concern in gas turbines, power plants, fertilizer plants, jet aircraft and civil aircraft. The military, gas turbine blades are affected by dust clouds ingestion and impingement of slurry particles. In this study, we investigated the erosion rate of Inconel 718 and Ti-6Al-4V turbine blades in the air jet-erosion test rig by ([Formula: see text]m) silica erodent. The primary process parameters, such as velocity (100 and 150[Formula: see text]m/s), impingement angle (30–90∘), feed rate (5–10[Formula: see text]g/min), temperature (30–650∘C) and standoff distance (10–50[Formula: see text]mm) were optimized using response surface methodology (RSM). The design of experiments (DOE) and experimental screening tests were performed to identify the significant process parameters on the erosion of turbine blade materials. To optimize the process parameters, the experiment was conducted to obtain a lowest erosion rate. The ploughing and cutting mechanism of both Inconel 718 and Ti-6Al-4V materials were identified through a scanning electron microscope. As a result, the erosion rate increases with an increase in velocity and temperature; however, the erosion rate decreases with an increase in the impingement angle. The experimental analysis showed that the erosion rate ranged between 0.051–1.914[Formula: see text]mg/g for Inconel 718 and 0.02–1.0095[Formula: see text]mg/g for Ti-6Al-4V.
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- 2021
15. Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes in Allogeneic Stem Cell Transplantation Patients with Early Coronavirus Disease 2019 Infection.
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Lee BJ, Vittayawacharin P, Griffin SP, Doh J, Nam HH, Jeyakumar D, Blodget E, Kongtim P, and Ciurea SO
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Adult, Aged, COVID-19 mortality, COVID-19 immunology, COVID-19 therapy, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Immune Reconstitution, SARS-CoV-2 immunology, Transplantation, Homologous adverse effects
- Abstract
Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplantation-related complications in the first year post-transplantation, owing in part to the profound immune dysregulation with T cell and B cell lymphopenia and functional impairment. Although several large studies have reported higher mortality rates from Coronavirus disease 2019 (COVID-19) in HSCT recipients, to date no study has focused on the impact of early COVID-19 infection on immune reconstitution post-transplantation and the correlation with transplantation outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection, with a median time to diagnosis of 100 days post-transplantation. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% confidence interval [CI], 1.26 to 13.05; P = .019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P = .001). This was attributed mainly to higher nonrelapse mortality (NRM) among early COVID-19 patients (P = .042). Allogeneic HSCT recipients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P = .021), CD3
+ CD4+ cell (95% CI, -105.35 to -11.59; P = .042), CD3+ CD8+ cell (95% CI, -324.55 to -57.13; P = .038), and CD3- CD56+ cell (95% CI, -193.51 to -47.31; P = .014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impaired immune reconstitution post-transplantation., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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16. Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.
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Litzow MR, Sun Z, Mattison RJ, Paietta EM, Roberts KG, Zhang Y, Racevskis J, Lazarus HM, Rowe JM, Arber DA, Wieduwilt MJ, Liedtke M, Bergeron J, Wood BL, Zhao Y, Wu G, Chang TC, Zhang W, Pratz KW, Dinner SN, Frey N, Gore SD, Bhatnagar B, Atallah EL, Uy GL, Jeyakumar D, Lin TL, Willman CL, DeAngelo DJ, Patel SB, Elliott MA, Advani AS, Tzachanis D, Vachhani P, Bhave RR, Sharon E, Little RF, Erba HP, Stone RM, Luger SM, Mullighan CG, and Tallman MS
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- Humans, Adult, Middle Aged, Male, Female, Aged, Consolidation Chemotherapy, Remission Induction, Disease-Free Survival, Kaplan-Meier Estimate, Survival Analysis, Recurrence, Antineoplastic Agents therapeutic use, Antineoplastic Agents adverse effects, Induction Chemotherapy, Antibodies, Bispecific adverse effects, Antibodies, Bispecific therapeutic use, Antibodies, Bispecific administration & dosage, Neoplasm, Residual, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects
- Abstract
Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission., Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1 -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point., Results: The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P = 0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group., Conclusions: The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.)., (Copyright © 2024 Massachusetts Medical Society.)
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- 2024
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17. Extending duration of letermovir prophylaxis in haploidentical stem cell transplantation.
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Vittayawacharin P, Lee BJ, Griffin S, Doh J, Smith J, Nam H, Blodget E, Jeyakumar D, Kongtim P, and Ciurea SO
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Not available.
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- 2024
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18. HyperCVAD versus pegaspargase-containing regimens for Hispanic adults with newly diagnosed B-cell acute lymphoblastic leukemia.
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Lee BJ, Griffin SP, Doh J, Chan A, Ciurea SO, Jeyakumar D, Fleischman AG, Naqvi K, Pannunzio NR, O'Brien S, and Kongtim P
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- Young Adult, Humans, Male, Adult, Asparaginase adverse effects, Polyethylene Glycols adverse effects, Retrospective Studies, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Objective: There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). Recent studies have demonstrated favorable outcomes of pegaspargase-containing ALL regimens (PEG-CAR) in young adults however, outcomes in Hispanic ethnicity continue to be underreported., Methods: We evaluated outcomes of newly diagnosed, adult B-cell ALL Hispanic and non-Hispanic patients consecutively treated with a PEG-CAR or HyperCVAD between January 2011 and November 2022. The primary endpoint was event-free survival (EFS) while secondary endpoints included cumulative incidence of relapse and overall survival (OS)., Results: Among 105 included patients, 48 (45.7%) were treated with a PEG-CAR and 57 (54.3%) with HyperCVAD. Median age was 38 years (range, 18-75 years), 61% were Hispanic, and 35.2% had poor-genetic risk. Hispanic patients demonstrated significantly worse 5-year EFS with a PEG-CAR compared to that seen with HyperCVAD (HR, 2.58; 95% CI, 1.32-5.04; p = .006) whereas non-Hispanic patients had better outcomes with PIR (52.4% vs. 42.0%). Hispanic ethnicity (p = .015) and male sex (p = .019) were independent predictors for poor OS., Conclusions: Hispanic patients with B-cell ALL had worse EFS with a PEG-CAR as compared with HyperCVAD. Future studies will aim to confirm these findings and establish a tailored treatment approach for this high-risk population., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2024
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19. Measurable residual disease conversion rate with consolidation chemotherapy in acute myeloid leukemia.
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Gaut D, Oliai C, Boiarsky J, Zhang S, Salhotra A, Azenkot T, Kennedy VE, Khanna V, Olmedo Gutierrez K, Shukla N, Moskoff B, Park G, Afkhami M, Patel A, Jeyakumar D, Mannis G, Logan AC, Jonas BA, and Schiller G
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- Humans, Consolidation Chemotherapy, Retrospective Studies, Remission Induction, Cytarabine, Neoplasm, Residual diagnosis, Prognosis, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Hematopoietic Stem Cell Transplantation
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The rate of MRD clearance in AML with standard consolidation chemotherapy is not well defined. A multi-institution retrospective analysis was performed on 107 consecutively treated AML patients in morphologic complete remission with detectable MRD post-induction therapy who received standard chemotherapy consolidation. In response to standard intermediate/high-dose cytarabine consolidation therapy, 26 of 60 patients (43.3%) with MRD threshold of detection of at least 0.1% converted to MRD-negative status (undetectable with assay used), and 6 of 47 patients (12.8%) with MRD threshold of detection > 0.1% converted to MRD-negative status. Multivariable logistic regression for patients with MRD threshold of detection of at least 0.1% showed that, when controlling for age, ELN risk category, dose of cytarabine, and use of a combination agent, treatment with 1 cycle of consolidation cytarabine versus ≥2 cycles decreased the odds of conversion of AML to MRD-negative (OR = 0.24, 95% CI 0.07-0.85, p = 0.03).
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- 2024
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20. Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results.
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Daver NG, Vyas P, Kambhampati S, Al Malki MM, Larson RA, Asch AS, Mannis G, Chai-Ho W, Tanaka TN, Bradley TJ, Jeyakumar D, Wang ES, Sweet K, Kantarjian HM, Garcia-Manero G, Komrokji R, Xing G, Ramsingh G, Renard C, Zeidner JF, and Sallman DA
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- Humans, Antibodies, Monoclonal, Humanized therapeutic use, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Azacitidine, Leukemia, Myeloid, Acute drug therapy
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Purpose: Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479)., Patients and Methods: Patients with previously untreated AML, including TP53 -mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m
2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR)., Results: Eighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53 -mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was -0.9 g/dL (range, -3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53- mutant and wild-type patients were 9.8 months and 18.9 months, respectively., Conclusion: Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.- Published
- 2023
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21. Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series.
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Griffin SP, Lee B, Doh J, Paradyse AR, Jeyakumar D, Arter Z, Nam H, Blodget E, Smith J, Valek A, Vittayawacharin P, Kongtim P, and Ciurea SO
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Introduction: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals., Case Presentations: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2). Patients 3 and 4 (strategy 3) did not experience elevated tacrolimus concentrations on NIM/r treatment with complete discontinuation of tacrolimus and azole antifungal and a 12-24-h delay in NIM/r initiation. Reinitiation of tacrolimus after NIM/r completion resulted in variable tacrolimus concentrations., Conclusion: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy., (© 2023 S. Karger AG, Basel.)
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- 2023
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22. Glasdegib plus intensive or non-intensive chemotherapy for untreated acute myeloid leukemia: results from the randomized, phase 3 BRIGHT AML 1019 trial.
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Sekeres MA, Montesinos P, Novak J, Wang J, Jeyakumar D, Tomlinson B, Mayer J, Jou E, Robak T, Taussig DC, Dombret H, Merchant A, Shaik N, O'Brien T, Roh W, Liu X, Ma W, DiRienzo CG, Chan G, and Cortes JE
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- Humans, Antineoplastic Combined Chemotherapy Protocols adverse effects, Daunorubicin, Cytarabine, Azacitidine therapeutic use, Nausea drug therapy, Leukemia, Myeloid, Acute, Anemia drug therapy
- Abstract
This is the primary report of the randomized, placebo-controlled phase 3 BRIGHT AML 1019 clinical trial of glasdegib in combination with intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated acute myeloid leukemia. Overall survival (primary endpoint) was similar between the glasdegib and placebo arms in the intensive (n = 404; hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.782-1.408; two-sided p = 0.749) and non-intensive (n = 325; HR 0.99; 95% CI: 0.768-1.289; two-sided p = 0.969) studies. The proportion of patients who experienced treatment-emergent adverse events was similar for glasdegib versus placebo (intensive: 99.0% vs. 98.5%; non-intensive: 99.4% vs. 98.8%). The most common treatment-emergent adverse events were nausea, febrile neutropenia, and anemia in the intensive study and anemia, constipation, and nausea in the non-intensive study. The addition of glasdegib to either cytarabine and daunorubicin or azacitidine did not significantly improve overall survival and the primary efficacy endpoint for the BRIGHT AML 1019 phase 3 trial was not met. Clinical trial registration: ClinicalTrials.gov: NCT03416179., (© 2023. The Author(s).)
- Published
- 2023
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23. A phase 1b study of venetoclax and alvocidib in patients with relapsed/refractory acute myeloid leukemia.
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Jonas BA, Hou JZ, Roboz GJ, Alvares CL, Jeyakumar D, Edwards JR, Erba HP, Kelly RJ, Röllig C, Fiedler W, Brackman D, Siddani SR, Chyla B, Hilger-Rolfe J, and Watts JM
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- Humans, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute etiology
- Abstract
Relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) is a genetically complex and heterogeneous disease with a poor prognosis and limited treatment options. Thus, there is an urgent need to develop therapeutic combinations to overcome drug resistance in AML. This open-label, multicenter, international, phase 1b study evaluated the safety, efficacy, and pharmacokinetics of venetoclax in combination with alvocidib in patients with R/R AML. Patients were treated with escalating doses of venetoclax (400, 600, and 800 mg QD, orally, days 1-28) and alvocidib (45 and 60 mg/m
2 , intravenously, days 1-3) in 28-day cycles. The combination was found to be safe and tolerable, with no maximum tolerated dose reached. Drug-related Grade ≥3 adverse events were reported in 23 (65.7%) for venetoclax and 24 (68.6%) for alvocidib. No drug-related AEs were fatal. Gastrointestinal toxicities, including diarrhea, nausea, and vomiting were notable and frequent; otherwise, the toxicities reported were consistent with the safety profile of both agents. The response rate was modest (complete remission [CR] + incomplete CR [CRi], 11.4%; CR + CRi + partial response rate + morphologic leukemia-free state, 20%). There was no change in alvocidib pharmacokinetics with increasing doses of venetoclax. However, when venetoclax was administered with alvocidib, AUC24 and Cmax decreased by 18% and 19%, respectively. A recommended phase 2 dose was not established due to lack of meaningful increase in efficacy across all cohorts compared to what was previously observed with each agent alone. Future studies could consider the role of the sequence, dosing, and the use of a more selective MCL1 inhibitor for the R/R AML population., (© 2023 AbbVie Inc. Hematological Oncology published by John Wiley & Sons Ltd.)- Published
- 2023
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24. Characterization of phenyl propiolic acid from Proteus mirabilis DMTMMR-11 and Evaluation of its mode of action against Yersinia enterocolitica (MTCC-840) an in-Vitro and in-Vivo based approach.
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Ravindran DR, Kannan S, Jeyakumar D, and Marudhamuthu M
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- Animals, Humans, Proteus mirabilis, Caenorhabditis elegans, Spectroscopy, Fourier Transform Infrared, Yersinia enterocolitica, Yersinia Infections microbiology
- Abstract
Foodborne illnesses are pervasive in raising public health concerns in both developed and developing nations. Yersinia enterocolitica a zoonotic bacterial species that causes food-transmitted infections, and gastroenteritis, is its most prevalent clinical manifestation. This study aims to investigate the differences, dependencies, and inhibitory mechanisms between the host and the microbiome. Proteus mirabilis DMTMMR-11, the bacterium found in the human gastrointestinal tract was used for the extraction of intracellular metabolite, because of its beneficial effects on the normal flora of the human gut. Phenyl propiolic acid was identified as the dominant compound in the metabolite after characterization using FT-IR, NMR, and LC-MS-MS. To assess its inhibitory mechanism against Yersinia enterocolitica, the pathogen was subjected to biological characterization by MBC and MIC, resulting in the rate of inhibition at 50 μg/ml. Anti-bacterial curve supports the inhibited growth of Y. enterocolitica. Mechanism of inhibition at its cellular level was indicated by the increase in alkaline phosphate content, which drastically reduced the cell membrane and cell wall potential expanding its permeability by intruding the membrane proteins, which was observed in SEM Imaging. Phenyl propiolic acid efficiently disrupts the biofilm formation by reducing the adherence and increasing the eradication property of the pathogen by exhibiting 65% of inhibition at the minimal duration of 12h. In-vivo study was carried out through host-pathogen interaction in C. elegans, an efficient model organism assessed for its life-span, physiological, and behavioral assays., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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25. Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3.
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Shah BD, Cassaday RD, Park JH, Houot R, Oluwole OO, Logan AC, Boissel N, Leguay T, Bishop MR, Topp MS, Tzachanis D, O'Dwyer KM, Arellano ML, Lin Y, Baer MR, Schiller GJ, Subklewe M, Abedi M, Minnema MC, Wierda WG, DeAngelo DJ, Stiff PJ, Jeyakumar D, Mao D, Adhikary S, Zhou L, Schuberth PC, Damico Khalid R, and Ghobadia A
- Subjects
- Humans, Adult, Immunotherapy, Adoptive, Adaptor Proteins, Signal Transducing, Antigens, CD19, Cytokine Release Syndrome, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Background: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported., Methods: Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided., Results: Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22)., Conclusions: In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel., Competing Interests: Competing interests: BS reports honoraria from Acrotech Biopharma, BeiGene, Gilead Sciences, Janssen, Pharmacyclics, and Spectrum; consulting/advisory role for Adaptive Biotechnologies; Amgen; Celgene/BMS; Kite, a Gilead Company; Novartis; Pfizer; and Precision BioSciences; research funding from Gilead Sciences, Incyte, Jazz Pharmaceuticals, and Kite; and travel support from Celgene, Janssen, Kite, Novartis, Pfizer, Seattle Genetics, and Stemline Therapeutics. RC reports spouse employment with Seagen; stock or other ownership in Seagen; honoraria from Amgen, Autolus (board member), PeproMene Bio (board member), Pfizer, and Kite; consultancy/advisory role for Amgen and Jazz; and research funding from Pfizer, Merck, Amgen, Servier, Kite, and Vanda. JHP reports consulting/advisory role for AstraZeneca, Kite, and Novartis and research funding from Amgen, Genentech, and Juno. RH reports honoraria from ADC therapeutics, Bristol Myers Squibb, Celgene, Gilead Sciences, Janssen, Kite, MSD, Novartis, and Roche; and consulting/advisory role for Kite/Gilead. OOO reports consulting/advisory role for Pfizer, Kite, Gilead, AbbVie, Janssen, TG Therapeutics, ADC, Novartis, Epizyme, Curio Science, Nektar, and Syncopation; research funding from Kite, Pfizer, Daiichi Sankyo, and Allogene; and honoraria from Pfizer and Gilead. ACL reports consulting/advisory role for AbbVie, Bristol Myers Squibb, and Pfizer; research funding from Amgen, Amphivena, Astellas, Autolus, Jazz, Kadmon, Kite, and Pharmacyclics. NB reports honoraria from and consulting/advisory role for Gilead Sciences. TL reports consultancy/advisory role for Amgen and Servier. MRBi reports honoraria from Incyte, Bristol Myers Squibb, Sanofi, and ADC Therapeutics; consulting/advisory role for Novartis, Kite/Gilead, Bristol Myers Squibb, Sana Bio, and CRISPR Therapeutics; and speakers’ bureau participation for Incyte, Bristol Myers Squibb, Sanofi, and ADC Therapeutics. MST reports consulting/advisory role for Amgen, Celgene, Kite, Regeneron, and Roche and research funding from Amgen, Kite, MacroGenics, Regeneron, and Roche. DT reports consulting/advisory role for Bristol Myers Squibb, EUSA, Partner, and Takeda; and research funding from Bristol Myers Squibb. KMO reports consulting/advisory role for Beam Therapeutics. MLA reports consulting/advisory role for Kite and Syndax Pharmaceuticals, Inc. and research funding from Kite (institutional PI). YL reports consulting/advisory role for Kite/Gilead, Celgene/BMS, Juno/BMS, bluebird bio, Janssen, Legend Biotech, Gamida Cell, Novartis, Iovance, Takeda, Fosun Kite, and Pfizer and research funding from Kite/Gilead, Celgene/BMS, bluebird bio, Janssen, Legend Biotech, Merck, Takeda, and Boston Scientific. MRBa reports research funding from AbbVie, Ascentage, Kite, Kura, and Takeda. GJS reports honoraria and research funding from and speakers’ bureau participation for Kite. MS reports consulting/advisory role for Amgen, Celgene/BMS, Gilead Sciences, Janssen, and Novartis; speakers’ bureau participation for Celgene/BMS, Gilead Sciences, Janssen, and Novartis; research funding from Amgen, Gilead Sciences, Miltenyi Biotec, MorphoSys, Roche, and Seattle Genetics; and travel support from Takeda. MA reports stock or other ownership in CytoDyn; consulting/advisory role for Celgene; and speakers’ bureau participation for Celgene, Bristol Myers Squibb, AbbVie, and Kite. MCM reports consulting/advisory role for Gilead Sciences and Janssen-Cilag and speakers’ bureau participation for Janssen-Cilag and Medscape. WW reports consulting/advisory role for Genzyme and Sanofi and research funding from AbbVie, Acerta, Cyclacel, Genentech, Gilead Sciences, GSK, Janssen, Juno, Karyopharm, Loxo Oncology, miRagen, Novartis, Oncternal, Pharmacyclics, Sunesis, and Xencor. DJD reports consulting or advisory role for Agios, Amgen, Autolus, Blueprint Medicines, Forty Seven, Gilead Sciences, Incyte, Jazz, Novartis, Pfizer, Shire, and Takeda and research funding from AbbVie, Glycomimetics, Novartis, and Blueprint Medicines. PJS reports honoraria from and consulting or advisory role for MorphoSys and CRISPR Therapeutics and research funding from Amgen, Gamida Cell, Pfizer, Karyopharm, Gilead Sciences, Incyte, Seagen, and Cellectar. DJ reports research funding from Jazz Pharmaceuticals and Pfizer. DM has nothing to report. SA reports employment with and stock or other ownership in Kite. LZ reports employment with Kite and ownership of AbbVie RSU or stock in the past 2 years. reports employment with Kite; stock or other ownership in Gilead Sciences; and travel support from Kite and Gilead Sciences. RDK reports employment, stock, or other ownership in Kite. AG reports consulting/advisory role for Amgen, Atara, Bristol Myers Squibb, CRISPR Therapeutics, Kite, and Wugen Inc.; research funding from Amgen, Genentech, and Kite; and honoraria from Kite., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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26. Impact of triple intrathecal prophylaxis in acute lymphoblastic leukemia adults receiving HyperCVAD: A COVID-19 practice change.
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Lee BJ, Kongtim P, Doh J, Griffin SP, Chan A, O'Brien S, Ciurea SO, and Jeyakumar D
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- Humans, Adult, Retrospective Studies, Pandemics, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide therapeutic use, Methotrexate therapeutic use, Recurrence, Vincristine adverse effects, COVID-19 epidemiology, COVID-19 prevention & control, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms prevention & control
- Abstract
Treatment of acute lymphoblastic leukemia (ALL) requires both systemically and locally directed therapies to prevent central nervous system (CNS) recurrence. In response to restrictions brought on by the COVID-19 pandemic, our institution adopted triple intrathecal (IT) chemotherapy for CNS prophylaxis during HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). We retrospectively reviewed records of newly diagnosed adult all patients who were consecutively treated with HyperCVAD between January 2011 and July 2022. Outcomes of patients who received triple IT chemotherapy and standard of care (SOC) CNS prophylaxis were compared. The primary endpoint was CNS relapse-free survival (RFS) while secondary endpoints included cumulative incidence of relapse, overall survival, number of outpatient, and total ITs per patient, and CNS treatment-related toxicities. A total of 37 patients including 21 in the triple IT and 16 in the SOC cohorts were evaluated. There were no differences between the triple IT and SOC cohorts with respect to CNS-RFS (89.6% vs. 80.4%; HR, 1.55; 95% CI, 0.45-5.39; p = .49), cumulative incidence of relapse (8.9% vs. 19.6%; HR, 1.14; 95% CI, 0.3-5.3; p = .87), and overall survival (89.6% vs. 85.7%; HR, 0.91; 95% CI, 0.20-4.21; p = .90) at 2-years. Significantly fewer IT doses were administered in the triple IT cohort (p = .011) and the number of additional outpatient appointments to administer IT chemotherapy were markedly reduced as 98.6% of IT doses were administered during scheduled admissions compared to 76.8% (p < .001). The adoption of triple IT chemotherapy did not increase CNS treatment-related toxicities but rather, the inverse was observed. Triple IT chemotherapy during HyperCVAD represents a feasible alternative to SOC CNS prophylaxis, especially during times of resource restriction and when minimization of patient exposures is desired., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2023
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27. Once-Daily Foscarnet Is Effective for Human Herpesvirus 6 Reactivation after Hematopoietic Stem Cell Transplantation.
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Vittayawacharin P, E'Leimat G, Lee BJ, Griffin S, Doh J, Nam H, Blodget E, Jeyakumar D, Kongtim P, and Ciurea SO
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- Adult, Humans, Young Adult, Middle Aged, Aged, Adolescent, Foscarnet therapeutic use, Transplantation, Homologous, DNA, Viral, Herpesvirus 6, Human physiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2023
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28. Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study.
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Sallman DA, Al Malki MM, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN, Zeidner JF, Garcia-Manero G, Jeyakumar D, Komrokji R, Lancet J, Kantarjian HM, Gu L, Zhang Y, Tan A, Chao M, O'Hear C, Ramsingh G, Lal I, Vyas P, and Daver NG
- Subjects
- Humans, Azacitidine, Antibodies, Monoclonal, Humanized therapeutic use, Progression-Free Survival, Treatment Outcome, Myelodysplastic Syndromes drug therapy, Leukemia, Myeloid, Acute drug therapy
- Abstract
Purpose: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479)., Patients and Methods: Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once-weekly or once-every-2-week maintenance dose. Azacitidine 75 mg/m
2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and complete remission (CR) rate., Results: Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was -0.7 g/dL (range, -3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53 -mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS., Conclusion: Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).- Published
- 2023
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29. Timing of intrathecal chemotherapy and blinatumomab impacts neurotoxicity in acute lymphoblastic leukemia.
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Lee BJ, Griffin SP, Doh J, Kongtim P, Chan A, O'Brien S, Jeyakumar D, and Ciurea SO
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- Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Antineoplastic Agents adverse effects, Antibodies, Bispecific adverse effects, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
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- 2023
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30. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia.
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Advani AS, Moseley A, O'Dwyer KM, Wood BL, Park J, Wieduwilt M, Jeyakumar D, Yaghmour G, Atallah EL, Gerds AT, O'Brien SM, Liesveld JL, Othus M, Litzow M, Stone RM, Sharon E, and Erba HP
- Subjects
- Humans, Aged, Aged, 80 and over, Dasatinib adverse effects, Prednisone therapeutic use, Treatment Outcome, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Novel treatment strategies are needed for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell-engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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31. Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study.
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Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, Leguay T, Bishop MR, Topp MS, Tzachanis D, O'Dwyer KM, Arellano ML, Lin Y, Baer MR, Schiller GJ, Park JH, Subklewe M, Abedi M, Minnema MC, Wierda WG, DeAngelo DJ, Stiff P, Jeyakumar D, Dong J, Adhikary S, Zhou L, Schuberth PC, Faghmous I, Masouleh BK, and Houot R
- Subjects
- Humans, Adult, Immunotherapy, Adoptive methods, Retrospective Studies, Historically Controlled Study, Recurrence, Antigens, CD19 therapeutic use, Receptors, Chimeric Antigen, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care., Methods: Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 10
6 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3., Results: After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients (N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with > 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients (N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 (N = 49) and matched historical controls (N = 40) was 25.4 and 5.5 months, respectively., Conclusions: These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population., Trial Registration: NCT02614066., (© 2022. The Author(s).)- Published
- 2022
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32. Increased incidence of Pegaspargase-induced hypertriglyceridemia and associated pancreatitis observed in the Hispanic adult patient population.
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Lee BJ, Doh J, Chan A, Jeyakumar D, and O'Brien S
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- Adult, Humans, Incidence, Hispanic or Latino, Acute Disease, Hypertriglyceridemia etiology, Hypertriglyceridemia complications, Pancreatitis chemically induced, Pancreatitis diagnosis, Pancreatitis epidemiology
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- 2022
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33. CD19-directed immunotherapy use in KMT2A-rearranged acute leukemia: A case report and literature review of increased lymphoid to myeloid lineage switch.
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Lee BJ, Griffin SP, Doh J, Chan A, O'Brien S, Jeyakumar D, Ciurea SO, Becker PS, and Kongtim P
- Subjects
- Humans, Cell Lineage, Immunotherapy, Gene Rearrangement, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Published
- 2022
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