Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576
Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed b...
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| Format: | Article |
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2022-01-01
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| Series: | Advances in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2022/4450824 |
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| author | Januario E. Castro Paula A. Lengerke-Diaz Juliana Velez Lujan Michael Y. Choi Eider F. Moreno-Cortes Jose V. Forero Juan Esteban Garcia-Robledo Chaja Jacobs Colin McCarthy Alaina Heinen Carlos I. Amaya-Chanaga Thomas J. Kipps |
| author_facet | Januario E. Castro Paula A. Lengerke-Diaz Juliana Velez Lujan Michael Y. Choi Eider F. Moreno-Cortes Jose V. Forero Juan Esteban Garcia-Robledo Chaja Jacobs Colin McCarthy Alaina Heinen Carlos I. Amaya-Chanaga Thomas J. Kipps |
| author_sort | Januario E. Castro |
| collection | DOAJ |
| description | Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768). |
| format | Article |
| id | doaj-art-4b490b66d62e48f895bce6b2d0f5c71a |
| institution | Kabale University |
| issn | 1687-9112 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Hematology |
| spelling | doaj-art-4b490b66d62e48f895bce6b2d0f5c71a2025-08-20T03:36:26ZengWileyAdvances in Hematology1687-91122022-01-01202210.1155/2022/4450824Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576Januario E. Castro0Paula A. Lengerke-Diaz1Juliana Velez Lujan2Michael Y. Choi3Eider F. Moreno-Cortes4Jose V. Forero5Juan Esteban Garcia-Robledo6Chaja Jacobs7Colin McCarthy8Alaina Heinen9Carlos I. Amaya-Chanaga10Thomas J. Kipps11Division of Hematology and Medical OncologyDivision of Hematology and Medical OncologyCLL Research Consortium (CRC)CLL Research Consortium (CRC)Division of Hematology and Medical OncologyDivision of Hematology and Medical OncologyDivision of Hematology and Medical OncologyMoores Cancer CenterMoores Cancer CenterMoores Cancer CenterEisai Inc.CLL Research Consortium (CRC)Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768).http://dx.doi.org/10.1155/2022/4450824 |
| spellingShingle | Januario E. Castro Paula A. Lengerke-Diaz Juliana Velez Lujan Michael Y. Choi Eider F. Moreno-Cortes Jose V. Forero Juan Esteban Garcia-Robledo Chaja Jacobs Colin McCarthy Alaina Heinen Carlos I. Amaya-Chanaga Thomas J. Kipps Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576 Advances in Hematology |
| title | Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576 |
| title_full | Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576 |
| title_fullStr | Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576 |
| title_full_unstemmed | Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576 |
| title_short | Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576 |
| title_sort | ibrutinib plus obinutuzumab as frontline therapy for chronic lymphocytic leukemia is associated with a lower rate of infusion related reactions and with sustained remissions after ibrutinib discontinuation a single arm open label phase 1b 2 clinical trial nct0231576 |
| url | http://dx.doi.org/10.1155/2022/4450824 |
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