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Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL
Bruton tyrosine kinase inhibitors (BTKi) and venetoclax are currently used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually develop resistance to these therapies, underscoring the need for effectiv...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652916/ https://www.ncbi.nlm.nih.gov/pubmed/34699592 http://dx.doi.org/10.1182/blood.2021011895 |
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author | Siddiqi, Tanya Soumerai, Jacob D. Dorritie, Kathleen A. Stephens, Deborah M. Riedell, Peter A. Arnason, Jon Kipps, Thomas J. Gillenwater, Heidi H. Gong, Lucy Yang, Lin Ogasawara, Ken Thorpe, Jerill Wierda, William G. |
author_facet | Siddiqi, Tanya Soumerai, Jacob D. Dorritie, Kathleen A. Stephens, Deborah M. Riedell, Peter A. Arnason, Jon Kipps, Thomas J. Gillenwater, Heidi H. Gong, Lucy Yang, Lin Ogasawara, Ken Thorpe, Jerill Wierda, William G. |
author_sort | Siddiqi, Tanya |
collection | PubMed |
description | Bruton tyrosine kinase inhibitors (BTKi) and venetoclax are currently used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually develop resistance to these therapies, underscoring the need for effective new therapies. We report results of the phase 1 dose-escalation portion of the multicenter, open-label, phase 1/2 TRANSCEND CLL 004 (NCT03331198) study of lisocabtagene maraleucel (liso-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory CLL/SLL. Patients with standard- or high-risk features treated with ≥3 or ≥2 prior therapies, respectively, including a BTKi, received liso-cel at 1 of 2 dose levels (50 × 10(6) or 100 × 10(6) CAR(+) T cells). Primary objectives included safety and determining recommended dose; antitumor activity by 2018 International Workshop on CLL guidelines was exploratory. Minimal residual disease (MRD) was assessed in blood and marrow. Twenty-three of 25 enrolled patients received liso-cel and were evaluable for safety. Patients had a median of 4 (range, 2-11) prior therapies (100% had ibrutinib; 65% had venetoclax) and 83% had high-risk features including mutated TP53 and del(17p). Seventy-four percent of patients had cytokine release syndrome (9% grade 3) and 39% had neurological events (22% grade 3/4). Of 22 efficacy-evaluable patients, 82% and 45% achieved overall and complete responses, respectively. Of 20 MRD-evaluable patients, 75% and 65% achieved undetectable MRD in blood and marrow, respectively. Safety and efficacy were similar between dose levels. The phase 2 portion of the study is ongoing at 100 × 10(6) CAR(+) T cells. This trial was registered at clinicaltrials.gov as NCT03331198. |
format | Online Article Text |
id | pubmed-10652916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106529162021-10-28 Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL Siddiqi, Tanya Soumerai, Jacob D. Dorritie, Kathleen A. Stephens, Deborah M. Riedell, Peter A. Arnason, Jon Kipps, Thomas J. Gillenwater, Heidi H. Gong, Lucy Yang, Lin Ogasawara, Ken Thorpe, Jerill Wierda, William G. Blood Clinical Trials and Observations Bruton tyrosine kinase inhibitors (BTKi) and venetoclax are currently used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually develop resistance to these therapies, underscoring the need for effective new therapies. We report results of the phase 1 dose-escalation portion of the multicenter, open-label, phase 1/2 TRANSCEND CLL 004 (NCT03331198) study of lisocabtagene maraleucel (liso-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory CLL/SLL. Patients with standard- or high-risk features treated with ≥3 or ≥2 prior therapies, respectively, including a BTKi, received liso-cel at 1 of 2 dose levels (50 × 10(6) or 100 × 10(6) CAR(+) T cells). Primary objectives included safety and determining recommended dose; antitumor activity by 2018 International Workshop on CLL guidelines was exploratory. Minimal residual disease (MRD) was assessed in blood and marrow. Twenty-three of 25 enrolled patients received liso-cel and were evaluable for safety. Patients had a median of 4 (range, 2-11) prior therapies (100% had ibrutinib; 65% had venetoclax) and 83% had high-risk features including mutated TP53 and del(17p). Seventy-four percent of patients had cytokine release syndrome (9% grade 3) and 39% had neurological events (22% grade 3/4). Of 22 efficacy-evaluable patients, 82% and 45% achieved overall and complete responses, respectively. Of 20 MRD-evaluable patients, 75% and 65% achieved undetectable MRD in blood and marrow, respectively. Safety and efficacy were similar between dose levels. The phase 2 portion of the study is ongoing at 100 × 10(6) CAR(+) T cells. This trial was registered at clinicaltrials.gov as NCT03331198. The American Society of Hematology 2022-03-24 2021-10-28 /pmc/articles/PMC10652916/ /pubmed/34699592 http://dx.doi.org/10.1182/blood.2021011895 Text en Copyright © 2022 American Society of Hematology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Clinical Trials and Observations Siddiqi, Tanya Soumerai, Jacob D. Dorritie, Kathleen A. Stephens, Deborah M. Riedell, Peter A. Arnason, Jon Kipps, Thomas J. Gillenwater, Heidi H. Gong, Lucy Yang, Lin Ogasawara, Ken Thorpe, Jerill Wierda, William G. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL |
title | Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL |
title_full | Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL |
title_fullStr | Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL |
title_full_unstemmed | Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL |
title_short | Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL |
title_sort | phase 1 transcend cll 004 study of lisocabtagene maraleucel in patients with relapsed/refractory cll or sll |
topic | Clinical Trials and Observations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652916/ https://www.ncbi.nlm.nih.gov/pubmed/34699592 http://dx.doi.org/10.1182/blood.2021011895 |
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