Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial
PURPOSE The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients. METHODS This is a m...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/187044 |
| Acceso en línea: | https://hdl.handle.net/2445/187044 |
| Access Level: | acceso abierto |
| Palabra clave: | Rituximab Limfomes Assaigs clínics Lymphomas Clinical trials |
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Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II TrialGiné Soca, EvaCruz, Fátima de laJiménez Ubieto, AnaLópez Jimenez, JavierMartín García-Sancho, AlejandroTerol, M. JoséGonzález Barca, EvaCasanova, MaríaFuente, Adolfo de laMarín Niebla, AnaMuntañola, AnaGonzález López, Tomás JoséAymerich Gregorio, MartaSetoain Perego, XavierCortés Romera, MontserratRotger, AmandaRodríguez, SoniaMedina Herrera, AlejandroGarcía Sanz, RamónNadeu Prat, FerranBeà Bobet, Sílvia M.Campo Güerri, EliasLópez Guillermo, ArmandoThe GELTAMO GroupRituximabLimfomesAssaigs clínicsRituximabLymphomasClinical trialsPURPOSE The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients. METHODS This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 12 Spanish GELTAMO sites (ClinicalTrials.gov identifier: NCT02682641). Previously untreated MCL patients with indolent clinical forms defined by the following criteria were eligible: no disease-related symptoms, nonblastoid variants, Ki-67 < 30%, and largest tumor diameter <= 3 cm. Both leukemic non-nodal and nodal subtypes were recruited. Patients received ibrutinib 560 mg once daily and a total of eight doses of rituximab 375 mg/m(2). Ibrutinib could be discontinued after 2 years in the case of sustained undetectable minimal residual disease (MRD). The primary end point was the complete response (CR) rate achieved after 12 cycles according to Lugano criteria. RESULTS Fifty patients with MCL (male 66%; median age 65 years) were enrolled. After 12 cycles of treatment, 42 (84%; 95% CI, 74 to 94) patients had an overall response, including 40 (80%; 95% CI, 69 to 91) with CR. Moreover, undetectable MRD in peripheral blood was achieved in 87% (95% CI, 77 to 97) of cases. At 2 years, 24 of 35 evaluable patients (69%) could discontinue ibrutinib because of undetectable MRD. Four patients had disease progression; three were non-nodal MCL and carried high genomic complexity and TP53 mutations at enrollment. No unexpected toxicity was seen except one patient with severe aplastic anemia. CONCLUSION Frontline IR combination achieves a high rate of CRs and undetectable MRD in indolent clinical forms of MCL. Discontinuation seems appropriate in cases with undetectable MRD, except for TP53-mutated cases.American Society of Clinical Oncology (ASCO)2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/187044Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1200/JCO.21.02321Journal of Clinical Oncology, 2022, vol. 40, num. 11, p. 1196-1205https://doi.org/10.1200/JCO.21.02321cc by-nc-nd (c) Giné, Eva et al., 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1870442026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| title |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| spellingShingle |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial Giné Soca, Eva Rituximab Limfomes Assaigs clínics Rituximab Lymphomas Clinical trials |
| title_short |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| title_full |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| title_fullStr |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| title_full_unstemmed |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| title_sort |
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial |
| dc.creator.none.fl_str_mv |
Giné Soca, Eva Cruz, Fátima de la Jiménez Ubieto, Ana López Jimenez, Javier Martín García-Sancho, Alejandro Terol, M. José González Barca, Eva Casanova, María Fuente, Adolfo de la Marín Niebla, Ana Muntañola, Ana González López, Tomás José Aymerich Gregorio, Marta Setoain Perego, Xavier Cortés Romera, Montserrat Rotger, Amanda Rodríguez, Sonia Medina Herrera, Alejandro García Sanz, Ramón Nadeu Prat, Ferran Beà Bobet, Sílvia M. Campo Güerri, Elias López Guillermo, Armando The GELTAMO Group |
| author |
Giné Soca, Eva |
| author_facet |
Giné Soca, Eva Cruz, Fátima de la Jiménez Ubieto, Ana López Jimenez, Javier Martín García-Sancho, Alejandro Terol, M. José González Barca, Eva Casanova, María Fuente, Adolfo de la Marín Niebla, Ana Muntañola, Ana González López, Tomás José Aymerich Gregorio, Marta Setoain Perego, Xavier Cortés Romera, Montserrat Rotger, Amanda Rodríguez, Sonia Medina Herrera, Alejandro García Sanz, Ramón Nadeu Prat, Ferran Beà Bobet, Sílvia M. Campo Güerri, Elias López Guillermo, Armando The GELTAMO Group |
| author_role |
author |
| author2 |
Cruz, Fátima de la Jiménez Ubieto, Ana López Jimenez, Javier Martín García-Sancho, Alejandro Terol, M. José González Barca, Eva Casanova, María Fuente, Adolfo de la Marín Niebla, Ana Muntañola, Ana González López, Tomás José Aymerich Gregorio, Marta Setoain Perego, Xavier Cortés Romera, Montserrat Rotger, Amanda Rodríguez, Sonia Medina Herrera, Alejandro García Sanz, Ramón Nadeu Prat, Ferran Beà Bobet, Sílvia M. Campo Güerri, Elias López Guillermo, Armando The GELTAMO Group |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Rituximab Limfomes Assaigs clínics Rituximab Lymphomas Clinical trials |
| topic |
Rituximab Limfomes Assaigs clínics Rituximab Lymphomas Clinical trials |
| description |
PURPOSE The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients. METHODS This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 12 Spanish GELTAMO sites (ClinicalTrials.gov identifier: NCT02682641). Previously untreated MCL patients with indolent clinical forms defined by the following criteria were eligible: no disease-related symptoms, nonblastoid variants, Ki-67 < 30%, and largest tumor diameter <= 3 cm. Both leukemic non-nodal and nodal subtypes were recruited. Patients received ibrutinib 560 mg once daily and a total of eight doses of rituximab 375 mg/m(2). Ibrutinib could be discontinued after 2 years in the case of sustained undetectable minimal residual disease (MRD). The primary end point was the complete response (CR) rate achieved after 12 cycles according to Lugano criteria. RESULTS Fifty patients with MCL (male 66%; median age 65 years) were enrolled. After 12 cycles of treatment, 42 (84%; 95% CI, 74 to 94) patients had an overall response, including 40 (80%; 95% CI, 69 to 91) with CR. Moreover, undetectable MRD in peripheral blood was achieved in 87% (95% CI, 77 to 97) of cases. At 2 years, 24 of 35 evaluable patients (69%) could discontinue ibrutinib because of undetectable MRD. Four patients had disease progression; three were non-nodal MCL and carried high genomic complexity and TP53 mutations at enrollment. No unexpected toxicity was seen except one patient with severe aplastic anemia. CONCLUSION Frontline IR combination achieves a high rate of CRs and undetectable MRD in indolent clinical forms of MCL. Discontinuation seems appropriate in cases with undetectable MRD, except for TP53-mutated cases. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/187044 |
| url |
https://hdl.handle.net/2445/187044 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1200/JCO.21.02321 Journal of Clinical Oncology, 2022, vol. 40, num. 11, p. 1196-1205 https://doi.org/10.1200/JCO.21.02321 |
| dc.rights.none.fl_str_mv |
cc by-nc-nd (c) Giné, Eva et al., 2022 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by-nc-nd (c) Giné, Eva et al., 2022 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ |
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openAccess |
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application/pdf |
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American Society of Clinical Oncology (ASCO) |
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American Society of Clinical Oncology (ASCO) |
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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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