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Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma

P. Sonneveld, S. Zweegman, M. Cavo, K. Nasserinejad, A. Broijl, R. Troia, L. Pour, S. Croockewit, P. Corradini, F. Patriarca, K. Wu, J. Droogendijk, G. Bos, R. Hajek, M. Teresa Petrucci, P. Ypma, N. Zojer, MC. Minnema, M. Boccadoro

. 2022 ; 6 (10) : e786. [pub] 20220930

Status neindexováno Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22031636

This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.

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$a This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.
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$a Zweegman, Sonja $u Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam Cancer Center, The Netherlands
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$a Cavo, Michele $u IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli," Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università degli Studi, Bologna, Italy
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$a Nasserinejad, Kazem $u Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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$a Broijl, Annemiek $u Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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$a Troia, Rosella $u Hematology, University of Torino, Italy
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$a Pour, Ludek $u Hematology, University Hospital, Brno, Czech Republic
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$a Croockewit, Sandra $u Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands
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$a Corradini, Paolo $u Hematology Division and Hemato-Oncology Department, University of Milan, Fondazione IRCCS Istituto Nazionale dei Tumori, Italy
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$a Patriarca, Francesca $u Hematology and Bone Marrow Transplant Unit, University of Udine, Italy
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$a Wu, Kalung $u Hematology, ZNA Stuivenberg, Antwerpen, Belgium
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$a Droogendijk, Jolanda $u Hematology, Elisabeth Tweesteden Hospital, Tilburg, The Netherlands
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$a Bos, Gerard $u Department of Hematology, University of Maastricht Medical Center, The Netherlands
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$a Hajek, Roman $u Department of Hematology, Ostrava Poruba FNO, Czech Republic
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$a Teresa Petrucci, Maria $u Department of Hematology, La Sapienza, Rome, Italy
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$a Ypma, Paula $u Department of Hematology, Haga Hospital, The Hague, The Netherlands
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$a Zojer, Nicholas $u Department of Hematology, Wilhelminen Hospital, Vienna, Austria
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$a Minnema, Monique C $u Department of Hematology, University Medical Center Utrecht, Utrecht University, The Netherlands
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$a Boccadoro, Mario $u Department of Molecular Biotechnologies and Health Sciences, Hematology Division, University of Torino, Italy $u Division of Hematology, Città della Salute e della Scienza, Università di Torino, Italy
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