Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma
Background Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepleti...
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BMJ Publishing Group
2024-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/7/e008975.full |
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| author | Crystal Mackall Holden T Maecker Lekha Mikkilineni Melody Smith Saurabh Dahiya Bita Sahaf David Miklos Sally Arai Surbhi Sidana Wen-Kai Weng Dasom Lee Anmol Goyal Sushma Bharadwaj Eric Lau Mark P Hamilton Hrishi Srinagesh Alexandria Jensen Jayasindhu Mallampet Sarah Elkordy Shriya Syal Sunita Patil Theresa Latchford Laura J Johnston Robert Lowsky Robert Negrin Andrew R Rezvani Judith Shizuru Everett H Meyer Parveen Shiraz Lori Muffly Matthew J Frank |
| author_facet | Crystal Mackall Holden T Maecker Lekha Mikkilineni Melody Smith Saurabh Dahiya Bita Sahaf David Miklos Sally Arai Surbhi Sidana Wen-Kai Weng Dasom Lee Anmol Goyal Sushma Bharadwaj Eric Lau Mark P Hamilton Hrishi Srinagesh Alexandria Jensen Jayasindhu Mallampet Sarah Elkordy Shriya Syal Sunita Patil Theresa Latchford Laura J Johnston Robert Lowsky Robert Negrin Andrew R Rezvani Judith Shizuru Everett H Meyer Parveen Shiraz Lori Muffly Matthew J Frank |
| author_sort | Crystal Mackall |
| collection | DOAJ |
| description | Background Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.Methods 84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.Results Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.Conclusions Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution. |
| format | Article |
| id | doaj-art-4eeab2b9098d4e108c29937f804ef916 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-4eeab2b9098d4e108c29937f804ef9162025-08-20T03:00:03ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-07-0112710.1136/jitc-2024-008975Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphomaCrystal Mackall0Holden T Maecker1Lekha Mikkilineni2Melody Smith3Saurabh Dahiya4Bita Sahaf5David Miklos6Sally Arai7Surbhi Sidana8Wen-Kai Weng9Dasom Lee10Anmol Goyal11Sushma Bharadwaj12Eric Lau13Mark P Hamilton14Hrishi Srinagesh15Alexandria Jensen16Jayasindhu Mallampet17Sarah Elkordy18Shriya Syal19Sunita Patil20Theresa Latchford21Laura J Johnston22Robert Lowsky23Robert Negrin24Andrew R Rezvani25Judith Shizuru26Everett H Meyer27Parveen Shiraz28Lori Muffly29Matthew J Frank30Stanford University, Stanford, California, USAStanford University, Stanford, California, USAStanford University School of Medicine, Stanford, California, USA25 The University of Auckland, Auckland, New Zealand9Stanford Medicine, Stanford, CA, USACancer Institute, Stanford University School of Medicine, Palo Alto, California, USAStanford University, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USADepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USADepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USADepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USADepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford Medicine, Palo Alto, California, USAStanford University School of Medicine, Stanford, California, USAStanford University School of Medicine, Stanford, California, USAStanford University, Palo Alto, California, USAStanford University School of Medicine, Stanford, California, USABackground Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.Methods 84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.Results Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.Conclusions Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.https://jitc.bmj.com/content/12/7/e008975.full |
| spellingShingle | Crystal Mackall Holden T Maecker Lekha Mikkilineni Melody Smith Saurabh Dahiya Bita Sahaf David Miklos Sally Arai Surbhi Sidana Wen-Kai Weng Dasom Lee Anmol Goyal Sushma Bharadwaj Eric Lau Mark P Hamilton Hrishi Srinagesh Alexandria Jensen Jayasindhu Mallampet Sarah Elkordy Shriya Syal Sunita Patil Theresa Latchford Laura J Johnston Robert Lowsky Robert Negrin Andrew R Rezvani Judith Shizuru Everett H Meyer Parveen Shiraz Lori Muffly Matthew J Frank Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma Journal for ImmunoTherapy of Cancer |
| title | Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma |
| title_full | Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma |
| title_fullStr | Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma |
| title_full_unstemmed | Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma |
| title_short | Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma |
| title_sort | bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large b cell lymphoma |
| url | https://jitc.bmj.com/content/12/7/e008975.full |
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