Consolidation with First and Second Allogeneic Transplants in Adults with Relapsed/Refractory B-ALL Following Response to CD19CAR T Cell Therapy
•AlloHCT post CAR-T response is feasible and associated with low early NRM.•AlloHCT outcomes in CAR-T responders were encouraging in high-risk r/r B-ALL.•Encouraging outcomes extend to CAR-T responders undergoing second transplant. CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has l...
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creator | Aldoss, Ibrahim Shan, Haoyue Yang, Dongyun Clark, Mary C. Al Malki, Monzr Aribi, Ahmed Agrawal, Vaibhav Sandhu, Karamjeet Salhotra, Amandeep Pourhassan, Hoda Koller, Paul Ali, Haris Artz, Andrew Karras, Nicole Pawlowska, Anna B. Murphy, Lindsey Palmer, Joycelynne Stein, Anthony Marcucci, Guido Pullarkat, Vinod Nakamura, Ryotaro Forman, Stephen J. |
description | •AlloHCT post CAR-T response is feasible and associated with low early NRM.•AlloHCT outcomes in CAR-T responders were encouraging in high-risk r/r B-ALL.•Encouraging outcomes extend to CAR-T responders undergoing second transplant.
CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy. We performed a retrospective analysis of adult patients with r/r B-ALL who responded to either investigational or standard of care (SOC) CD19-targeted CAR-T therapy and underwent consolidation with alloHCT while in CR without interim therapy. We identified 45 patients, of whom 26 (58%) and 19 (42%) received their first and second alloHCT as consolidation post CAR-T therapy, respectively. The median age was 31 years (range: 19-67) and 31 (69%) patients were Hispanic. Ph-like was the most common genetic subtype and comprised over half of cases (53%; n = 24). The median number of prior therapies pre-transplant was 5 (range: 2-7), and disease status at the time of alloHCT was CR1, CR2 or ≥CR3 in 7 (16%), 22 (49%) and 16 (35%) patients, respectively. The median time from CAR-T therapy until alloHCT was 93 (range: 42-262) days. The conditioning regimen was radiation-based myeloablative (MAC) in 22 (49%) patients. With a median follow-up of 2.47 years (range: 0.13-6.93), 2-year overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 57.3% (95% CI: 0.432-0.760), 56.2% (95% CI: 0.562-0.745), 23.3% (95% CI: 0.13-0.42), and 20.4% (95% CI: 0.109-0.384), respectively. Two-year OS (52% vs. 68%, P = .641), RFS (54% vs. 59%, P = .820), CIR (33.5% vs. 8.5%, P = .104), and NRM (12.5% vs. 32.2%, P = .120) were not significantly different between patients who underwent their first vs. second transp |
doi_str_mv | 10.1016/j.jtct.2024.06.013 |
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CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy. We performed a retrospective analysis of adult patients with r/r B-ALL who responded to either investigational or standard of care (SOC) CD19-targeted CAR-T therapy and underwent consolidation with alloHCT while in CR without interim therapy. We identified 45 patients, of whom 26 (58%) and 19 (42%) received their first and second alloHCT as consolidation post CAR-T therapy, respectively. The median age was 31 years (range: 19-67) and 31 (69%) patients were Hispanic. Ph-like was the most common genetic subtype and comprised over half of cases (53%; n = 24). The median number of prior therapies pre-transplant was 5 (range: 2-7), and disease status at the time of alloHCT was CR1, CR2 or ≥CR3 in 7 (16%), 22 (49%) and 16 (35%) patients, respectively. The median time from CAR-T therapy until alloHCT was 93 (range: 42-262) days. The conditioning regimen was radiation-based myeloablative (MAC) in 22 (49%) patients. With a median follow-up of 2.47 years (range: 0.13-6.93), 2-year overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 57.3% (95% CI: 0.432-0.760), 56.2% (95% CI: 0.562-0.745), 23.3% (95% CI: 0.13-0.42), and 20.4% (95% CI: 0.109-0.384), respectively. Two-year OS (52% vs. 68%, P = .641), RFS (54% vs. 59%, P = .820), CIR (33.5% vs. 8.5%, P = .104), and NRM (12.5% vs. 32.2%, P = .120) were not significantly different between patients who underwent their first vs. second transplant, respectively. In univariate analysis, only Ph-like genotype was associated with inferior RFS (P = .03). AlloHCT post CAR-T response is associated with a relatively low early mortality rate and encouraging survival results in high-risk adults with r/r B-ALL, extending to the second alloHCT for fit and eligible patients.</description><identifier>ISSN: 2666-6367</identifier><identifier>EISSN: 2666-6367</identifier><identifier>DOI: 10.1016/j.jtct.2024.06.013</identifier><identifier>PMID: 38876428</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute lymphoblastic leukemia ; Allogeneic hematopoietic cell transplantation ; CD19 CAR T cells</subject><ispartof>Transplantation and cellular therapy, 2024-08, Vol.30 (8), p.788.e1-788.e9</ispartof><rights>2024 The American Society for Transplantation and Cellular Therapy</rights><rights>Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-598a66a8214ba7ec4005978b91d1f1654874ef0ab169b5366b57ee72ac0167013</cites><orcidid>0000-0003-3862-4612 ; 0000-0001-9466-6396 ; 0000-0001-8024-8484 ; 0000-0002-9082-0680 ; 0000-0003-3599-3447 ; 0000-0003-0803-9607</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38876428$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aldoss, Ibrahim</creatorcontrib><creatorcontrib>Shan, Haoyue</creatorcontrib><creatorcontrib>Yang, Dongyun</creatorcontrib><creatorcontrib>Clark, Mary C.</creatorcontrib><creatorcontrib>Al Malki, Monzr</creatorcontrib><creatorcontrib>Aribi, Ahmed</creatorcontrib><creatorcontrib>Agrawal, Vaibhav</creatorcontrib><creatorcontrib>Sandhu, Karamjeet</creatorcontrib><creatorcontrib>Salhotra, Amandeep</creatorcontrib><creatorcontrib>Pourhassan, Hoda</creatorcontrib><creatorcontrib>Koller, Paul</creatorcontrib><creatorcontrib>Ali, Haris</creatorcontrib><creatorcontrib>Artz, Andrew</creatorcontrib><creatorcontrib>Karras, Nicole</creatorcontrib><creatorcontrib>Pawlowska, Anna B.</creatorcontrib><creatorcontrib>Murphy, Lindsey</creatorcontrib><creatorcontrib>Palmer, Joycelynne</creatorcontrib><creatorcontrib>Stein, Anthony</creatorcontrib><creatorcontrib>Marcucci, Guido</creatorcontrib><creatorcontrib>Pullarkat, Vinod</creatorcontrib><creatorcontrib>Nakamura, Ryotaro</creatorcontrib><creatorcontrib>Forman, Stephen J.</creatorcontrib><title>Consolidation with First and Second Allogeneic Transplants in Adults with Relapsed/Refractory B-ALL Following Response to CD19CAR T Cell Therapy</title><title>Transplantation and cellular therapy</title><addtitle>Transplant Cell Ther</addtitle><description>•AlloHCT post CAR-T response is feasible and associated with low early NRM.•AlloHCT outcomes in CAR-T responders were encouraging in high-risk r/r B-ALL.•Encouraging outcomes extend to CAR-T responders undergoing second transplant.
CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy. We performed a retrospective analysis of adult patients with r/r B-ALL who responded to either investigational or standard of care (SOC) CD19-targeted CAR-T therapy and underwent consolidation with alloHCT while in CR without interim therapy. We identified 45 patients, of whom 26 (58%) and 19 (42%) received their first and second alloHCT as consolidation post CAR-T therapy, respectively. The median age was 31 years (range: 19-67) and 31 (69%) patients were Hispanic. Ph-like was the most common genetic subtype and comprised over half of cases (53%; n = 24). The median number of prior therapies pre-transplant was 5 (range: 2-7), and disease status at the time of alloHCT was CR1, CR2 or ≥CR3 in 7 (16%), 22 (49%) and 16 (35%) patients, respectively. The median time from CAR-T therapy until alloHCT was 93 (range: 42-262) days. The conditioning regimen was radiation-based myeloablative (MAC) in 22 (49%) patients. With a median follow-up of 2.47 years (range: 0.13-6.93), 2-year overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 57.3% (95% CI: 0.432-0.760), 56.2% (95% CI: 0.562-0.745), 23.3% (95% CI: 0.13-0.42), and 20.4% (95% CI: 0.109-0.384), respectively. Two-year OS (52% vs. 68%, P = .641), RFS (54% vs. 59%, P = .820), CIR (33.5% vs. 8.5%, P = .104), and NRM (12.5% vs. 32.2%, P = .120) were not significantly different between patients who underwent their first vs. second transplant, respectively. In univariate analysis, only Ph-like genotype was associated with inferior RFS (P = .03). AlloHCT post CAR-T response is associated with a relatively low early mortality rate and encouraging survival results in high-risk adults with r/r B-ALL, extending to the second alloHCT for fit and eligible patients.</description><subject>Acute lymphoblastic leukemia</subject><subject>Allogeneic hematopoietic cell transplantation</subject><subject>CD19 CAR T cells</subject><issn>2666-6367</issn><issn>2666-6367</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kc1O3DAUha2KqiDKC3RRedlNgp0fO5HYhLQDSCNVmk7XluPcgEceO7U9oHkLHhlPB1BXXd27-M6x7zkIfaEkp4Syy02-iSrmBSmqnLCc0PIDOisYYxkrGT_5Zz9FFyFsCElkmTDyCZ2WTcNZVTRn6Ll3NjijRxm1s_hJxwe80D5ELO2If4FyaXTGuHuwoBVee2nDbKSNAWuLu3Fn0vZXtgIj5wDj5QomL1V0fo-vs265xAuXDJ60vU9MmNODgKPD_Xfa9t0Kr3EPxuD1A3g57z-jj5M0AS5e5zn6vfix7m-z5c-bu75bZqooeczqtpGMyaag1SA5qIqQuuXN0NKRTpTVVcMrmIgcKGuHumRsqDkAL6RK4fEUwzn6dvSdvfuzgxDFVgeVPiItuF0QJWENr-uqrBJaHFHlXQgeJjF7vZV-LygRhzLERhzKEIcyBGEi2SfR11f_3bCF8V3yFn0Cro4ApCsfNXgRlAarYNQektno9P_8XwCSppp5</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Aldoss, Ibrahim</creator><creator>Shan, Haoyue</creator><creator>Yang, Dongyun</creator><creator>Clark, Mary C.</creator><creator>Al Malki, Monzr</creator><creator>Aribi, Ahmed</creator><creator>Agrawal, Vaibhav</creator><creator>Sandhu, Karamjeet</creator><creator>Salhotra, Amandeep</creator><creator>Pourhassan, Hoda</creator><creator>Koller, Paul</creator><creator>Ali, Haris</creator><creator>Artz, Andrew</creator><creator>Karras, Nicole</creator><creator>Pawlowska, Anna B.</creator><creator>Murphy, Lindsey</creator><creator>Palmer, Joycelynne</creator><creator>Stein, Anthony</creator><creator>Marcucci, Guido</creator><creator>Pullarkat, Vinod</creator><creator>Nakamura, Ryotaro</creator><creator>Forman, Stephen J.</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3862-4612</orcidid><orcidid>https://orcid.org/0000-0001-9466-6396</orcidid><orcidid>https://orcid.org/0000-0001-8024-8484</orcidid><orcidid>https://orcid.org/0000-0002-9082-0680</orcidid><orcidid>https://orcid.org/0000-0003-3599-3447</orcidid><orcidid>https://orcid.org/0000-0003-0803-9607</orcidid></search><sort><creationdate>20240801</creationdate><title>Consolidation with First and Second Allogeneic Transplants in Adults with Relapsed/Refractory B-ALL Following Response to CD19CAR T Cell Therapy</title><author>Aldoss, Ibrahim ; 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CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT). Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy. We performed a retrospective analysis of adult patients with r/r B-ALL who responded to either investigational or standard of care (SOC) CD19-targeted CAR-T therapy and underwent consolidation with alloHCT while in CR without interim therapy. We identified 45 patients, of whom 26 (58%) and 19 (42%) received their first and second alloHCT as consolidation post CAR-T therapy, respectively. The median age was 31 years (range: 19-67) and 31 (69%) patients were Hispanic. Ph-like was the most common genetic subtype and comprised over half of cases (53%; n = 24). The median number of prior therapies pre-transplant was 5 (range: 2-7), and disease status at the time of alloHCT was CR1, CR2 or ≥CR3 in 7 (16%), 22 (49%) and 16 (35%) patients, respectively. The median time from CAR-T therapy until alloHCT was 93 (range: 42-262) days. The conditioning regimen was radiation-based myeloablative (MAC) in 22 (49%) patients. With a median follow-up of 2.47 years (range: 0.13-6.93), 2-year overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 57.3% (95% CI: 0.432-0.760), 56.2% (95% CI: 0.562-0.745), 23.3% (95% CI: 0.13-0.42), and 20.4% (95% CI: 0.109-0.384), respectively. Two-year OS (52% vs. 68%, P = .641), RFS (54% vs. 59%, P = .820), CIR (33.5% vs. 8.5%, P = .104), and NRM (12.5% vs. 32.2%, P = .120) were not significantly different between patients who underwent their first vs. second transplant, respectively. In univariate analysis, only Ph-like genotype was associated with inferior RFS (P = .03). AlloHCT post CAR-T response is associated with a relatively low early mortality rate and encouraging survival results in high-risk adults with r/r B-ALL, extending to the second alloHCT for fit and eligible patients.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38876428</pmid><doi>10.1016/j.jtct.2024.06.013</doi><orcidid>https://orcid.org/0000-0003-3862-4612</orcidid><orcidid>https://orcid.org/0000-0001-9466-6396</orcidid><orcidid>https://orcid.org/0000-0001-8024-8484</orcidid><orcidid>https://orcid.org/0000-0002-9082-0680</orcidid><orcidid>https://orcid.org/0000-0003-3599-3447</orcidid><orcidid>https://orcid.org/0000-0003-0803-9607</orcidid></addata></record> |
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subjects | Acute lymphoblastic leukemia Allogeneic hematopoietic cell transplantation CD19 CAR T cells |
title | Consolidation with First and Second Allogeneic Transplants in Adults with Relapsed/Refractory B-ALL Following Response to CD19CAR T Cell Therapy |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T04%3A11%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Consolidation%20with%20First%20and%20Second%20Allogeneic%20Transplants%20in%20Adults%20with%20Relapsed/Refractory%20B-ALL%20Following%20Response%20to%20CD19CAR%20T%20Cell%20Therapy&rft.jtitle=Transplantation%20and%20cellular%20therapy&rft.au=Aldoss,%20Ibrahim&rft.date=2024-08-01&rft.volume=30&rft.issue=8&rft.spage=788.e1&rft.epage=788.e9&rft.pages=788.e1-788.e9&rft.issn=2666-6367&rft.eissn=2666-6367&rft_id=info:doi/10.1016/j.jtct.2024.06.013&rft_dat=%3Cproquest_cross%3E3068755434%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3068755434&rft_id=info:pmid/38876428&rft_els_id=S2666636724004706&rfr_iscdi=true |