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A Real-World Comparison of CAR T-Cell Therapy Versus a Historical Standard-of-Care Approach for Relapsed-Refractory Large B-Cell Lymphoma in Ontario, Canada
Background Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for patients with relapsed-refractory large B-cell lymphoma (RR LBCL) after two lines of systemic therapy since December 2019. However, real-world evidence of CAR-T outcomes has been limited to s...
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| Published in: | Blood 2024-11, Vol.144 (Supplement 1), p.5134-5134 |
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| container_issue | Supplement 1 |
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| container_title | Blood |
| container_volume | 144 |
| creator | Kordbacheh, Tiana Prica, Anca Chan, Kelvin KW Aminilari, Mahmood Ante, Zharmaine Liu, Ning Gong, Inna Y Bhella, Sita Crump, Michael Vijenthira, Abi Kuruvilla, John Kridel, Robert Chen, Christine I Kukreti, Vishal Yang, Chloe Malik, Nauman Hodgson, David Rodin, Danielle |
| description | Background
Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for patients with relapsed-refractory large B-cell lymphoma (RR LBCL) after two lines of systemic therapy since December 2019. However, real-world evidence of CAR-T outcomes has been limited to small series with little comparison to prior standard-of-care management. We compared overall survival (OS), adverse events, and healthcare utilization for a cohort of patients with RR LBCL consecutively treated with CAR-T versus a cohort of historical controls treated with standard-of-care therapy prior to CAR-T approval.
Methods
This is a propensity-weighted retrospective cohort study of patients with RR LBCL treated at Princess Margaret (PM) Cancer Centre. Using linked clinical and administrative datasets, consecutive patients treated with CAR-T (2020-2022) following provincial funding approval were compared to a matched cohort of historical controls (2012-2017). Patients were followed from index date, defined as the date of progression following 2 lines of chemotherapy (2L) in the historical controls and following last therapy (2L or higher) in the CAR-T patients for up to 3-years, with maximum follow-up to March 31, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to account for confounding between cohorts (age, sex, lactate dehydrogenase, and comorbidities). Kaplan meier curves and IPTW-weighted Cox proportional hazard regression analyses estimated the adjusted hazard ratio (HR) between treatment cohort and OS. A landmark survival analysis of patients alive at 3 months post-index date addressed immortal time bias. Adverse events (AEs) from inpatient/emergency department [ED] diagnoses and healthcare utilization were reported per 1000 person-days at risk.
Results
A total of 86 CAR-T patients and 150 historical control patients were evaluable for comparison. Variables were balanced after applying the sIPTW (based on standardized difference |
| doi_str_mv | 10.1182/blood-2024-206375 |
| format | article |
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Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for patients with relapsed-refractory large B-cell lymphoma (RR LBCL) after two lines of systemic therapy since December 2019. However, real-world evidence of CAR-T outcomes has been limited to small series with little comparison to prior standard-of-care management. We compared overall survival (OS), adverse events, and healthcare utilization for a cohort of patients with RR LBCL consecutively treated with CAR-T versus a cohort of historical controls treated with standard-of-care therapy prior to CAR-T approval.
Methods
This is a propensity-weighted retrospective cohort study of patients with RR LBCL treated at Princess Margaret (PM) Cancer Centre. Using linked clinical and administrative datasets, consecutive patients treated with CAR-T (2020-2022) following provincial funding approval were compared to a matched cohort of historical controls (2012-2017). Patients were followed from index date, defined as the date of progression following 2 lines of chemotherapy (2L) in the historical controls and following last therapy (2L or higher) in the CAR-T patients for up to 3-years, with maximum follow-up to March 31, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to account for confounding between cohorts (age, sex, lactate dehydrogenase, and comorbidities). Kaplan meier curves and IPTW-weighted Cox proportional hazard regression analyses estimated the adjusted hazard ratio (HR) between treatment cohort and OS. A landmark survival analysis of patients alive at 3 months post-index date addressed immortal time bias. Adverse events (AEs) from inpatient/emergency department [ED] diagnoses and healthcare utilization were reported per 1000 person-days at risk.
Results
A total of 86 CAR-T patients and 150 historical control patients were evaluable for comparison. Variables were balanced after applying the sIPTW (based on standardized difference <0.1); mean age was 56 years and males comprised 61%. Prior treatment included ASCT in 27.6% CAR-T vs 38.4% historical control patients (standardized difference 0.21; p=0.09). Post-2L progression, 58% of historical controls had no further treatment, 32% received intravenous or oral chemotherapy/targeted agents, 6.2% had an autologous stem cell transplant, and 10% received palliative chemotherapy and/or radiotherapy. CAR-T patients received tisagenlecleucel (33.3%) and axicabtagene ciloleucel (66.7%) CAR-T products. The OS probabilities at 1-, 2-, and 3-years were 68% (95% CI 53-79%), 60% (95% CI 44-73%), and 57% (95% CI 39-71%), respectively, in the CAR-T group, and 18% (95% CI 12-25%), 11% (95% CI 7-17%), and 10% (95% CI 5-16%), respectively, in the control group. The IPTW-adjusted HR for all-cause death was 0.22 (95% CI 0.15-0.33), and landmark survival analysis for all-cause death 3-months post-index date to end of follow-up generated a similar HR of 0.28 (CI 0.19-0.44) in the CAR-T group.
CAR-T patients had a lower number of days hospitalized (77.73 [95% CI 75.00-80.57] vs 86.11 [95% CI 83.12-89.21] per 1000 person-day; p<0.001), ICU admissions (0.55 [95% CI 0.36-0.84] vs 1.26 [95% CI 0.94-1.69] per 1000 person-day; p=0.001), and ED visits (4.79 [95% CI 4.10-5.61] vs 2.07 [95% CI 1.65-2.60] per 1000 person-day; p<0.001). Additionally, CAR-T patients had lower events per 1000 person-days of: infection (1.44 [95% CI 1.10-1.87] vs 3.02 [95% CI 2.50-3.64] p<0.001), neutropenia (0.65 [95% CI 0.44-0.96] vs 1.79 [95% CI 1.4-2.29]; p<0.001), febrile neutropenia (0.45 [95% CI0.28-0.72] vs 1.47 [95% CI 1.12-1.92]; p<0.001), gastrointestinal toxicity (0.26 [95% CI 0.14-0.49] vs 0.69 [95% CI 0.46-1.02]), and respiratory infections (0.51 [95% CI 0.33-0.79] vs 0.91 [95% CI 0.65-1.29]; p=0.04).
Conclusions
CAR T-cell therapy produced a significant and sustained survival benefit versus historical standard-of-care management, with fewer hospitalizations and infections. Despite well-described CAR-T toxicities, historical control patients had more AEs, underscoring the lack of other effective salvage treatments. This study describes one of the largest real-world comparisons of patients with RR LBCL receiving CAR T-cell therapy compared to previous standard-of-care therapies and demonstrates its effectiveness amongst a broad cohort of eligible patients, consistent with the results of pivotal trials.
Bhella:Kite, Gilead: Consultancy, Honoraria. Crump:Roche: Research Funding; Epizyme/Ipsen: Research Funding; Canada's Drug Agency (CADTH): Honoraria; Kyte/Gilead: Honoraria. Kuruvilla:F. Hoffmann-La Roche Ltd, AstraZeneca, Merck, Novartis: Research Funding; DSMB Karyopharm: Other; AbbVie, Amgen, AstraZeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Seattle Genetics: Honoraria; AbbVie, BMS, Gilead, Merck, F. Hoffmann-La Roche Ltd, Seattle Genetics: Consultancy. Kridel:Acerta Pharma: Research Funding; AstraZeneca: Research Funding; Telix Pharmaceuticals: Current equity holder in publicly-traded company; Eisai: Other: Travel expenses; BMS: Research Funding; Abbvie: Research Funding; Roche: Research Funding; ITM Isotope Technologies Munich SE: Current equity holder in private company. Chen:Eli Lilly and Company: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astrazeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forus Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodin:Need Inc: Consultancy, Current holder of stock options in a privately-held company.]]></description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2024-206375</identifier><language>eng</language><publisher>Elsevier Inc</publisher><ispartof>Blood, 2024-11, Vol.144 (Supplement 1), p.5134-5134</ispartof><rights>2024 American Society of Hematology. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006497124078923$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27901,27902,45756</link.rule.ids></links><search><creatorcontrib>Kordbacheh, Tiana</creatorcontrib><creatorcontrib>Prica, Anca</creatorcontrib><creatorcontrib>Chan, Kelvin KW</creatorcontrib><creatorcontrib>Aminilari, Mahmood</creatorcontrib><creatorcontrib>Ante, Zharmaine</creatorcontrib><creatorcontrib>Liu, Ning</creatorcontrib><creatorcontrib>Gong, Inna Y</creatorcontrib><creatorcontrib>Bhella, Sita</creatorcontrib><creatorcontrib>Crump, Michael</creatorcontrib><creatorcontrib>Vijenthira, Abi</creatorcontrib><creatorcontrib>Kuruvilla, John</creatorcontrib><creatorcontrib>Kridel, Robert</creatorcontrib><creatorcontrib>Chen, Christine I</creatorcontrib><creatorcontrib>Kukreti, Vishal</creatorcontrib><creatorcontrib>Yang, Chloe</creatorcontrib><creatorcontrib>Malik, Nauman</creatorcontrib><creatorcontrib>Hodgson, David</creatorcontrib><creatorcontrib>Rodin, Danielle</creatorcontrib><title>A Real-World Comparison of CAR T-Cell Therapy Versus a Historical Standard-of-Care Approach for Relapsed-Refractory Large B-Cell Lymphoma in Ontario, Canada</title><title>Blood</title><description><![CDATA[Background
Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for patients with relapsed-refractory large B-cell lymphoma (RR LBCL) after two lines of systemic therapy since December 2019. However, real-world evidence of CAR-T outcomes has been limited to small series with little comparison to prior standard-of-care management. We compared overall survival (OS), adverse events, and healthcare utilization for a cohort of patients with RR LBCL consecutively treated with CAR-T versus a cohort of historical controls treated with standard-of-care therapy prior to CAR-T approval.
Methods
This is a propensity-weighted retrospective cohort study of patients with RR LBCL treated at Princess Margaret (PM) Cancer Centre. Using linked clinical and administrative datasets, consecutive patients treated with CAR-T (2020-2022) following provincial funding approval were compared to a matched cohort of historical controls (2012-2017). Patients were followed from index date, defined as the date of progression following 2 lines of chemotherapy (2L) in the historical controls and following last therapy (2L or higher) in the CAR-T patients for up to 3-years, with maximum follow-up to March 31, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to account for confounding between cohorts (age, sex, lactate dehydrogenase, and comorbidities). Kaplan meier curves and IPTW-weighted Cox proportional hazard regression analyses estimated the adjusted hazard ratio (HR) between treatment cohort and OS. A landmark survival analysis of patients alive at 3 months post-index date addressed immortal time bias. Adverse events (AEs) from inpatient/emergency department [ED] diagnoses and healthcare utilization were reported per 1000 person-days at risk.
Results
A total of 86 CAR-T patients and 150 historical control patients were evaluable for comparison. Variables were balanced after applying the sIPTW (based on standardized difference <0.1); mean age was 56 years and males comprised 61%. Prior treatment included ASCT in 27.6% CAR-T vs 38.4% historical control patients (standardized difference 0.21; p=0.09). Post-2L progression, 58% of historical controls had no further treatment, 32% received intravenous or oral chemotherapy/targeted agents, 6.2% had an autologous stem cell transplant, and 10% received palliative chemotherapy and/or radiotherapy. CAR-T patients received tisagenlecleucel (33.3%) and axicabtagene ciloleucel (66.7%) CAR-T products. The OS probabilities at 1-, 2-, and 3-years were 68% (95% CI 53-79%), 60% (95% CI 44-73%), and 57% (95% CI 39-71%), respectively, in the CAR-T group, and 18% (95% CI 12-25%), 11% (95% CI 7-17%), and 10% (95% CI 5-16%), respectively, in the control group. The IPTW-adjusted HR for all-cause death was 0.22 (95% CI 0.15-0.33), and landmark survival analysis for all-cause death 3-months post-index date to end of follow-up generated a similar HR of 0.28 (CI 0.19-0.44) in the CAR-T group.
CAR-T patients had a lower number of days hospitalized (77.73 [95% CI 75.00-80.57] vs 86.11 [95% CI 83.12-89.21] per 1000 person-day; p<0.001), ICU admissions (0.55 [95% CI 0.36-0.84] vs 1.26 [95% CI 0.94-1.69] per 1000 person-day; p=0.001), and ED visits (4.79 [95% CI 4.10-5.61] vs 2.07 [95% CI 1.65-2.60] per 1000 person-day; p<0.001). Additionally, CAR-T patients had lower events per 1000 person-days of: infection (1.44 [95% CI 1.10-1.87] vs 3.02 [95% CI 2.50-3.64] p<0.001), neutropenia (0.65 [95% CI 0.44-0.96] vs 1.79 [95% CI 1.4-2.29]; p<0.001), febrile neutropenia (0.45 [95% CI0.28-0.72] vs 1.47 [95% CI 1.12-1.92]; p<0.001), gastrointestinal toxicity (0.26 [95% CI 0.14-0.49] vs 0.69 [95% CI 0.46-1.02]), and respiratory infections (0.51 [95% CI 0.33-0.79] vs 0.91 [95% CI 0.65-1.29]; p=0.04).
Conclusions
CAR T-cell therapy produced a significant and sustained survival benefit versus historical standard-of-care management, with fewer hospitalizations and infections. Despite well-described CAR-T toxicities, historical control patients had more AEs, underscoring the lack of other effective salvage treatments. This study describes one of the largest real-world comparisons of patients with RR LBCL receiving CAR T-cell therapy compared to previous standard-of-care therapies and demonstrates its effectiveness amongst a broad cohort of eligible patients, consistent with the results of pivotal trials.
Bhella:Kite, Gilead: Consultancy, Honoraria. Crump:Roche: Research Funding; Epizyme/Ipsen: Research Funding; Canada's Drug Agency (CADTH): Honoraria; Kyte/Gilead: Honoraria. Kuruvilla:F. Hoffmann-La Roche Ltd, AstraZeneca, Merck, Novartis: Research Funding; DSMB Karyopharm: Other; AbbVie, Amgen, AstraZeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Seattle Genetics: Honoraria; AbbVie, BMS, Gilead, Merck, F. Hoffmann-La Roche Ltd, Seattle Genetics: Consultancy. Kridel:Acerta Pharma: Research Funding; AstraZeneca: Research Funding; Telix Pharmaceuticals: Current equity holder in publicly-traded company; Eisai: Other: Travel expenses; BMS: Research Funding; Abbvie: Research Funding; Roche: Research Funding; ITM Isotope Technologies Munich SE: Current equity holder in private company. Chen:Eli Lilly and Company: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astrazeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forus Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodin:Need Inc: Consultancy, Current holder of stock options in a privately-held company.]]></description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kEFu2zAQRYkiBeK4OUB3c4AyJSXRkpCVKyR1AAEGXKNZCiNyWDOQRWHoFvBdetgoddfZ_Fm9PzNPiM9a3WldZV_7IUYnM5UVc6zy0nwQC22ySiqVqSuxUEqtZFGX-lrcpPSilC7yzCzE3zXsCAf5HHlw0MTjhBxSHCF6aNY72MuGhgH2B2KczvCTOP1OgLAJ6RQ5WBzgxwlHh-xk9LJBJlhPE0e0B_CR5_YBp0RO7sgz2hk6Q4v8i-Dbpbo9H6dDPCKEEbbjaV4fv0CDIzr8JD56HBLd_p9LsX982Dcb2W6_PzXrVtq6MHNUPu9LnRu3Im2pMKWua0VVnbtCmbo3WVFleTl_T723tqrqslBOU-l6a43Pl0Jfai3HlJh8N3E4Ip87rbo3u90_u92b3e5id2buLwzNd_0JxF2ygUZLLjDZU-dieId-BZ-lgtY</recordid><startdate>20241105</startdate><enddate>20241105</enddate><creator>Kordbacheh, Tiana</creator><creator>Prica, Anca</creator><creator>Chan, Kelvin KW</creator><creator>Aminilari, Mahmood</creator><creator>Ante, Zharmaine</creator><creator>Liu, Ning</creator><creator>Gong, Inna Y</creator><creator>Bhella, Sita</creator><creator>Crump, Michael</creator><creator>Vijenthira, Abi</creator><creator>Kuruvilla, John</creator><creator>Kridel, Robert</creator><creator>Chen, Christine I</creator><creator>Kukreti, Vishal</creator><creator>Yang, Chloe</creator><creator>Malik, Nauman</creator><creator>Hodgson, David</creator><creator>Rodin, Danielle</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20241105</creationdate><title>A Real-World Comparison of CAR T-Cell Therapy Versus a Historical Standard-of-Care Approach for Relapsed-Refractory Large B-Cell Lymphoma in Ontario, Canada</title><author>Kordbacheh, Tiana ; Prica, Anca ; Chan, Kelvin KW ; Aminilari, Mahmood ; Ante, Zharmaine ; Liu, Ning ; Gong, Inna Y ; Bhella, Sita ; Crump, Michael ; Vijenthira, Abi ; Kuruvilla, John ; Kridel, Robert ; Chen, Christine I ; Kukreti, Vishal ; Yang, Chloe ; Malik, Nauman ; Hodgson, David ; Rodin, Danielle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c945-c98f3b7135d6e1ce4571990e893d4059b5248237497ebfcc889740d1e7dbcc5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kordbacheh, Tiana</creatorcontrib><creatorcontrib>Prica, Anca</creatorcontrib><creatorcontrib>Chan, Kelvin KW</creatorcontrib><creatorcontrib>Aminilari, Mahmood</creatorcontrib><creatorcontrib>Ante, Zharmaine</creatorcontrib><creatorcontrib>Liu, Ning</creatorcontrib><creatorcontrib>Gong, Inna Y</creatorcontrib><creatorcontrib>Bhella, Sita</creatorcontrib><creatorcontrib>Crump, Michael</creatorcontrib><creatorcontrib>Vijenthira, Abi</creatorcontrib><creatorcontrib>Kuruvilla, John</creatorcontrib><creatorcontrib>Kridel, Robert</creatorcontrib><creatorcontrib>Chen, Christine I</creatorcontrib><creatorcontrib>Kukreti, Vishal</creatorcontrib><creatorcontrib>Yang, Chloe</creatorcontrib><creatorcontrib>Malik, Nauman</creatorcontrib><creatorcontrib>Hodgson, David</creatorcontrib><creatorcontrib>Rodin, Danielle</creatorcontrib><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kordbacheh, Tiana</au><au>Prica, Anca</au><au>Chan, Kelvin KW</au><au>Aminilari, Mahmood</au><au>Ante, Zharmaine</au><au>Liu, Ning</au><au>Gong, Inna Y</au><au>Bhella, Sita</au><au>Crump, Michael</au><au>Vijenthira, Abi</au><au>Kuruvilla, John</au><au>Kridel, Robert</au><au>Chen, Christine I</au><au>Kukreti, Vishal</au><au>Yang, Chloe</au><au>Malik, Nauman</au><au>Hodgson, David</au><au>Rodin, Danielle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Real-World Comparison of CAR T-Cell Therapy Versus a Historical Standard-of-Care Approach for Relapsed-Refractory Large B-Cell Lymphoma in Ontario, Canada</atitle><jtitle>Blood</jtitle><date>2024-11-05</date><risdate>2024</risdate><volume>144</volume><issue>Supplement 1</issue><spage>5134</spage><epage>5134</epage><pages>5134-5134</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract><![CDATA[Background
Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for patients with relapsed-refractory large B-cell lymphoma (RR LBCL) after two lines of systemic therapy since December 2019. However, real-world evidence of CAR-T outcomes has been limited to small series with little comparison to prior standard-of-care management. We compared overall survival (OS), adverse events, and healthcare utilization for a cohort of patients with RR LBCL consecutively treated with CAR-T versus a cohort of historical controls treated with standard-of-care therapy prior to CAR-T approval.
Methods
This is a propensity-weighted retrospective cohort study of patients with RR LBCL treated at Princess Margaret (PM) Cancer Centre. Using linked clinical and administrative datasets, consecutive patients treated with CAR-T (2020-2022) following provincial funding approval were compared to a matched cohort of historical controls (2012-2017). Patients were followed from index date, defined as the date of progression following 2 lines of chemotherapy (2L) in the historical controls and following last therapy (2L or higher) in the CAR-T patients for up to 3-years, with maximum follow-up to March 31, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to account for confounding between cohorts (age, sex, lactate dehydrogenase, and comorbidities). Kaplan meier curves and IPTW-weighted Cox proportional hazard regression analyses estimated the adjusted hazard ratio (HR) between treatment cohort and OS. A landmark survival analysis of patients alive at 3 months post-index date addressed immortal time bias. Adverse events (AEs) from inpatient/emergency department [ED] diagnoses and healthcare utilization were reported per 1000 person-days at risk.
Results
A total of 86 CAR-T patients and 150 historical control patients were evaluable for comparison. Variables were balanced after applying the sIPTW (based on standardized difference <0.1); mean age was 56 years and males comprised 61%. Prior treatment included ASCT in 27.6% CAR-T vs 38.4% historical control patients (standardized difference 0.21; p=0.09). Post-2L progression, 58% of historical controls had no further treatment, 32% received intravenous or oral chemotherapy/targeted agents, 6.2% had an autologous stem cell transplant, and 10% received palliative chemotherapy and/or radiotherapy. CAR-T patients received tisagenlecleucel (33.3%) and axicabtagene ciloleucel (66.7%) CAR-T products. The OS probabilities at 1-, 2-, and 3-years were 68% (95% CI 53-79%), 60% (95% CI 44-73%), and 57% (95% CI 39-71%), respectively, in the CAR-T group, and 18% (95% CI 12-25%), 11% (95% CI 7-17%), and 10% (95% CI 5-16%), respectively, in the control group. The IPTW-adjusted HR for all-cause death was 0.22 (95% CI 0.15-0.33), and landmark survival analysis for all-cause death 3-months post-index date to end of follow-up generated a similar HR of 0.28 (CI 0.19-0.44) in the CAR-T group.
CAR-T patients had a lower number of days hospitalized (77.73 [95% CI 75.00-80.57] vs 86.11 [95% CI 83.12-89.21] per 1000 person-day; p<0.001), ICU admissions (0.55 [95% CI 0.36-0.84] vs 1.26 [95% CI 0.94-1.69] per 1000 person-day; p=0.001), and ED visits (4.79 [95% CI 4.10-5.61] vs 2.07 [95% CI 1.65-2.60] per 1000 person-day; p<0.001). Additionally, CAR-T patients had lower events per 1000 person-days of: infection (1.44 [95% CI 1.10-1.87] vs 3.02 [95% CI 2.50-3.64] p<0.001), neutropenia (0.65 [95% CI 0.44-0.96] vs 1.79 [95% CI 1.4-2.29]; p<0.001), febrile neutropenia (0.45 [95% CI0.28-0.72] vs 1.47 [95% CI 1.12-1.92]; p<0.001), gastrointestinal toxicity (0.26 [95% CI 0.14-0.49] vs 0.69 [95% CI 0.46-1.02]), and respiratory infections (0.51 [95% CI 0.33-0.79] vs 0.91 [95% CI 0.65-1.29]; p=0.04).
Conclusions
CAR T-cell therapy produced a significant and sustained survival benefit versus historical standard-of-care management, with fewer hospitalizations and infections. Despite well-described CAR-T toxicities, historical control patients had more AEs, underscoring the lack of other effective salvage treatments. This study describes one of the largest real-world comparisons of patients with RR LBCL receiving CAR T-cell therapy compared to previous standard-of-care therapies and demonstrates its effectiveness amongst a broad cohort of eligible patients, consistent with the results of pivotal trials.
Bhella:Kite, Gilead: Consultancy, Honoraria. Crump:Roche: Research Funding; Epizyme/Ipsen: Research Funding; Canada's Drug Agency (CADTH): Honoraria; Kyte/Gilead: Honoraria. Kuruvilla:F. Hoffmann-La Roche Ltd, AstraZeneca, Merck, Novartis: Research Funding; DSMB Karyopharm: Other; AbbVie, Amgen, AstraZeneca, BMS, Genmab, Gilead, Incyte, Janssen, Merck, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Seattle Genetics: Honoraria; AbbVie, BMS, Gilead, Merck, F. Hoffmann-La Roche Ltd, Seattle Genetics: Consultancy. Kridel:Acerta Pharma: Research Funding; AstraZeneca: Research Funding; Telix Pharmaceuticals: Current equity holder in publicly-traded company; Eisai: Other: Travel expenses; BMS: Research Funding; Abbvie: Research Funding; Roche: Research Funding; ITM Isotope Technologies Munich SE: Current equity holder in private company. Chen:Eli Lilly and Company: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astrazeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forus Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rodin:Need Inc: Consultancy, Current holder of stock options in a privately-held company.]]></abstract><pub>Elsevier Inc</pub><doi>10.1182/blood-2024-206375</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2024-11, Vol.144 (Supplement 1), p.5134-5134 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_elsevier_sciencedirect_doi_10_1182_blood_2024_206375 |
| source | ScienceDirect® |
| title | A Real-World Comparison of CAR T-Cell Therapy Versus a Historical Standard-of-Care Approach for Relapsed-Refractory Large B-Cell Lymphoma in Ontario, Canada |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T08%3A15%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Real-World%20Comparison%20of%20CAR%20T-Cell%20Therapy%20Versus%20a%20Historical%20Standard-of-Care%20Approach%20for%20Relapsed-Refractory%20Large%20B-Cell%20Lymphoma%20in%20Ontario,%20Canada&rft.jtitle=Blood&rft.au=Kordbacheh,%20Tiana&rft.date=2024-11-05&rft.volume=144&rft.issue=Supplement%201&rft.spage=5134&rft.epage=5134&rft.pages=5134-5134&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2024-206375&rft_dat=%3Celsevier_cross%3ES0006497124078923%3C/elsevier_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c945-c98f3b7135d6e1ce4571990e893d4059b5248237497ebfcc889740d1e7dbcc5f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |