Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

Ibrahim Aldoss; Gregory W. Roloff; Rawan Faramand; Noam E. Kopmar; Chenyu Lin; Anjali S. Advani; Simone E. Dekker; Vishal K. Gupta; Timothy E. O’Connor; Nikeshan Jeyakumar; Ibrahim N. Muhsen; Yannis Valtis; Amy Zhang; Katharine Miller; Katherine Sutherland; Kaitlyn C. Dykes; Mohamed Ahmed; Evan Chen; Hector Zambrano; Danielle Bradshaw; Santiago Mercadal; Marc Schwartz; Sean Tracy; Bhagirathbhai Dholaria; Michal Kubiak; Akash Mukherjee; Navneet Majhail; Minoo Battiwalla; Luke Mountjoy; Shahbaz A. Malik; John Mathews; Paul Shaughnessy; Aaron C. Logan; Abdullah Ladha; Maryann Stefan; Caitlin Guzowski; Rasmus T. Hoeg; Talal Hilal; Jozal Moore; Matthew Connor; Kristen M. O’Dwyer; La Quisa C. Hill; Stephanie B. Tsai; Joshua Sasine; Melhem M. Solh; Catherine J. Lee; Vamsi K. Kota; Divya Koura; Muthu Veeraputhiran; Betsy Blunk; Caspian Oliai; Jessica T. Leonard; Noelle V. Frey; Jae H. Park; Marlise R. Luskin; Veronika Bachanova; Ahmed Galal; Michael R. Bishop; Wendy Stock; Ryan D. Cassaday; Vinod Pullarkat; Bijal D. Shah; Lori S. Muffly

doi:10.1182/bloodadvances.2024013747

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

Ibrahim Aldoss, Gregory W. Roloff, Rawan Faramand, Noam E. Kopmar, Chenyu Lin, Anjali S. Advani, Simone E. Dekker, Vishal K. Gupta, Timothy E. O’Connor, Nikeshan Jeyakumar, Ibrahim N. Muhsen, Yannis Valtis, Amy Zhang, Katharine Miller, Katherine Sutherland, Kaitlyn C. Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle BradshawSantiago Mercadal, Marc Schwartz, Sean Tracy, Bhagirathbhai Dholaria, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A. Malik, John Mathews, Paul Shaughnessy, Aaron C. Logan, Abdullah Ladha, Maryann Stefan, Caitlin Guzowski, Rasmus T. Hoeg, Talal Hilal, Jozal Moore, Matthew Connor, Kristen M. O’Dwyer, La Quisa C. Hill, Stephanie B. Tsai, Joshua Sasine, Melhem M. Solh, Catherine J. Lee, Vamsi K. Kota, Divya Koura, Muthu Veeraputhiran, Betsy Blunk, Caspian Oliai, Jessica T. Leonard, Noelle V. Frey, Jae H. Park, Marlise R. Luskin, Veronika Bachanova, Ahmed Galal, Michael R. Bishop, Wendy Stock, Ryan D. Cassaday, Vinod Pullarkat, Bijal D. Shah, Lori S. Muffly

Medicine - Hematology, Oncology, Transplant

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2 Scopus citations

Abstract

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

Original language	English (US)
Pages (from-to)	6139-6147
Number of pages	9
Journal	Blood Advances
Volume	8
Issue number	23
DOIs	https://doi.org/10.1182/bloodadvances.2024013747
State	Published - Dec 10 2024

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© 2024 by The American Society of Hematology.

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Journal Article
Multicenter Study

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10.1182/bloodadvances.2024013747

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Aldoss, I., Roloff, G. W., Faramand, R., Kopmar, N. E., Lin, C., Advani, A. S., Dekker, S. E., Gupta, V. K., O’Connor, T. E., Jeyakumar, N., Muhsen, I. N., Valtis, Y., Zhang, A., Miller, K., Sutherland, K., Dykes, K. C., Ahmed, M., Chen, E., Zambrano, H., ... Muffly, L. S. (2024). Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL. Blood Advances, 8(23), 6139-6147. https://doi.org/10.1182/bloodadvances.2024013747

Aldoss, I, Roloff, GW, Faramand, R, Kopmar, NE, Lin, C, Advani, AS, Dekker, SE, Gupta, VK, O’Connor, TE, Jeyakumar, N, Muhsen, IN, Valtis, Y, Zhang, A, Miller, K, Sutherland, K, Dykes, KC, Ahmed, M, Chen, E, Zambrano, H, Bradshaw, D, Mercadal, S, Schwartz, M, Tracy, S, Dholaria, B, Kubiak, M, Mukherjee, A, Majhail, N, Battiwalla, M, Mountjoy, L, Malik, SA, Mathews, J, Shaughnessy, P, Logan, AC, Ladha, A, Stefan, M, Guzowski, C, Hoeg, RT, Hilal, T, Moore, J, Connor, M, O’Dwyer, KM, Hill, LQC, Tsai, SB, Sasine, J, Solh, MM, Lee, CJ, Kota, VK, Koura, D, Veeraputhiran, M, Blunk, B, Oliai, C, Leonard, JT, Frey, NV, Park, JH, Luskin, MR, Bachanova, V, Galal, A, Bishop, MR, Stock, W, Cassaday, RD, Pullarkat, V, Shah, BD & Muffly, LS 2024, 'Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL', Blood Advances, vol. 8, no. 23, pp. 6139-6147. https://doi.org/10.1182/bloodadvances.2024013747

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title = "Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL",

abstract = "The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-na{\"i}ve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-na{\"i}ve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.",

author = "Ibrahim Aldoss and Roloff, {Gregory W.} and Rawan Faramand and Kopmar, {Noam E.} and Chenyu Lin and Advani, {Anjali S.} and Dekker, {Simone E.} and Gupta, {Vishal K.} and O{\textquoteright}Connor, {Timothy E.} and Nikeshan Jeyakumar and Muhsen, {Ibrahim N.} and Yannis Valtis and Amy Zhang and Katharine Miller and Katherine Sutherland and Dykes, {Kaitlyn C.} and Mohamed Ahmed and Evan Chen and Hector Zambrano and Danielle Bradshaw and Santiago Mercadal and Marc Schwartz and Sean Tracy and Bhagirathbhai Dholaria and Michal Kubiak and Akash Mukherjee and Navneet Majhail and Minoo Battiwalla and Luke Mountjoy and Malik, {Shahbaz A.} and John Mathews and Paul Shaughnessy and Logan, {Aaron C.} and Abdullah Ladha and Maryann Stefan and Caitlin Guzowski and Hoeg, {Rasmus T.} and Talal Hilal and Jozal Moore and Matthew Connor and O{\textquoteright}Dwyer, {Kristen M.} and Hill, {La Quisa C.} and Tsai, {Stephanie B.} and Joshua Sasine and Solh, {Melhem M.} and Lee, {Catherine J.} and Kota, {Vamsi K.} and Divya Koura and Muthu Veeraputhiran and Betsy Blunk and Caspian Oliai and Leonard, {Jessica T.} and Frey, {Noelle V.} and Park, {Jae H.} and Luskin, {Marlise R.} and Veronika Bachanova and Ahmed Galal and Bishop, {Michael R.} and Wendy Stock and Cassaday, {Ryan D.} and Vinod Pullarkat and Shah, {Bijal D.} and Muffly, {Lori S.}",

note = "Publisher Copyright: {\textcopyright} 2024 by The American Society of Hematology.",

year = "2024",

month = dec,

day = "10",

doi = "10.1182/bloodadvances.2024013747",

language = "English (US)",

volume = "8",

pages = "6139--6147",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

number = "23",

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TY - JOUR

T1 - Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

AU - Aldoss, Ibrahim

AU - Roloff, Gregory W.

AU - Faramand, Rawan

AU - Kopmar, Noam E.

AU - Lin, Chenyu

AU - Advani, Anjali S.

AU - Dekker, Simone E.

AU - Gupta, Vishal K.

AU - O’Connor, Timothy E.

AU - Jeyakumar, Nikeshan

AU - Muhsen, Ibrahim N.

AU - Valtis, Yannis

AU - Zhang, Amy

AU - Miller, Katharine

AU - Sutherland, Katherine

AU - Dykes, Kaitlyn C.

AU - Ahmed, Mohamed

AU - Chen, Evan

AU - Zambrano, Hector

AU - Bradshaw, Danielle

AU - Mercadal, Santiago

AU - Schwartz, Marc

AU - Tracy, Sean

AU - Dholaria, Bhagirathbhai

AU - Kubiak, Michal

AU - Mukherjee, Akash

AU - Majhail, Navneet

AU - Battiwalla, Minoo

AU - Mountjoy, Luke

AU - Malik, Shahbaz A.

AU - Mathews, John

AU - Shaughnessy, Paul

AU - Logan, Aaron C.

AU - Ladha, Abdullah

AU - Stefan, Maryann

AU - Guzowski, Caitlin

AU - Hoeg, Rasmus T.

AU - Hilal, Talal

AU - Moore, Jozal

AU - Connor, Matthew

AU - O’Dwyer, Kristen M.

AU - Hill, La Quisa C.

AU - Tsai, Stephanie B.

AU - Sasine, Joshua

AU - Solh, Melhem M.

AU - Lee, Catherine J.

AU - Kota, Vamsi K.

AU - Koura, Divya

AU - Veeraputhiran, Muthu

AU - Blunk, Betsy

AU - Oliai, Caspian

AU - Leonard, Jessica T.

AU - Frey, Noelle V.

AU - Park, Jae H.

AU - Luskin, Marlise R.

AU - Bachanova, Veronika

AU - Galal, Ahmed

AU - Bishop, Michael R.

AU - Stock, Wendy

AU - Cassaday, Ryan D.

AU - Pullarkat, Vinod

AU - Shah, Bijal D.

AU - Muffly, Lori S.

PY - 2024/12/10

Y1 - 2024/12/10

N2 - The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

AB - The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

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U2 - 10.1182/bloodadvances.2024013747

DO - 10.1182/bloodadvances.2024013747

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C2 - 39093952

AN - SCOPUS:85210095224

SN - 2473-9529

VL - 8

SP - 6139

EP - 6147

JO - Blood Advances

JF - Blood Advances

IS - 23

ER -

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

Abstract

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UN SDGs

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