دورية أكاديمية
Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study.
| العنوان: | Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study. |
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| المؤلفون: | Stege CAM; Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands., Nasserinejad K; HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van der Spek E; Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands., Bilgin YM; Department of Internal Medicine, Admiraal de Ruijter Hospital, Goes, the Netherlands., Kentos A; Department of Hematology, Centre Hospitalier Jolimont, Haine-Saint-Paul, Belgium., Sohne M; Department of Internal Medicine/Hematology, St Antonius Hospital, Nieuwegein, the Netherlands., van Kampen RJW; Department of Internal Medicine, Zuyderland Medical Center, Sittard-Geleen, the Netherlands., Ludwig I; Department of Hematology, Bernhoven Hospital, Uden, the Netherlands., Thielen N; Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands., Durdu-Rayman N; Department of Internal Medicine-Hematology, Franciscus Hospital location Vlietland, Schiedam, the Netherlands., de Graauw NCHP; Department of Internal Medicine, Bravis Hospital, Roosendaal, the Netherlands., van de Donk NWCJ; Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands., de Waal EGM; Department of Internal Medicine, Medisch Centrum Leeuwarden, Leeuwarden, the Netherlands., Vekemans MC; Department of Hematology, St Luc Hospital, Bruxelles, Belgium., Timmers GJ; Department of Internal Medicine, Amstelland Hospital, Amstelveen, the Netherlands., van der Klift M; Department of Internal Medicine, Amphia Hospital, Breda, the Netherlands., Soechit S; Department of Hematology, Reinier de Graaf Groep, Delft, the Netherlands., Geerts PAF; Department of Internal Medicine, Deventer Hospital, Deventer, the Netherlands; Currently Isala, Zwolle, the Netherlands., Silbermann MH; Department of Internal Medicine, Tergooi Hospital, Hilversum, the Netherlands., Oosterveld M; Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands., Nijhof IS; Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands., Sonneveld P; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Klein SK; Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands., Levin MD; Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands., Zweegman S; Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2021 Sep 01; Vol. 39 (25), pp. 2758-2767. Date of Electronic Publication: 2021 May 04. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Quality of Life*, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use , Frail Elderly/*statistics & numerical data , Multiple Myeloma/*drug therapy, Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage ; Boron Compounds/administration & dosage ; Dexamethasone/administration & dosage ; Female ; Follow-Up Studies ; Glycine/administration & dosage ; Glycine/analogs & derivatives ; Humans ; Male ; Multiple Myeloma/pathology ; Prognosis ; Prospective Studies ; Survival Rate |
| مستخلص: | Purpose: Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex). Methods: Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years. Results: The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles. Conclusion: Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance. Competing Interests: Ellen van der SpekOther Relationship: Amgen Alain KentosConsulting or Advisory Role: Amgen, Sanofi, Janssen-Cilag Niels W. C. J. van de DonkConsulting or Advisory Role: Janssen, Celgene, Bristol Myers Squibb, Novartis, Amgen, Servier, Takeda, BayerSpeakers' Bureau: Janssen Research & Development, Celgene, Amgen, Bristol Myers SquibbResearch Funding: Janssen, Celgene, Amgen, Novartis, Bristol Myers Squibb, Cellectis Esther G. M. de WaalSpeakers' Bureau: CelgeneTravel, Accommodations, Expenses: Roche Marie-Christiane VekemansConsulting or Advisory Role: Amgen, Celgene, Bristol Myers Squibb, Janssen, TakedaTravel, Accommodations, Expenses: Amgen, Bristol Myers Squibb, Teva, Janssen Gert Jan TimmersConsulting or Advisory Role: Daiichi Sankyo Ned, Janssen-CilagSpeakers' Bureau: Novartis, ServierTravel, Accommodations, Expenses: Gilead Sciences Paul A. F. GeertsHonoraria: SanofiConsulting or Advisory Role: Janssen-Cilag Inger S. NijhofConsulting or Advisory Role: Janssen, Celgene/Bristol Myers Squibb Pieter SonneveldConsulting or Advisory Role: Celgene, Janssen, Amgen, Karyopharm Therapeutics, CARsgen TherapeuticsResearch Funding: Janssen, Amgen, Skyline Diagnostics Mark-David LevinHonoraria: AbbVie, Celgene, Janssen, TakedaTravel, Accommodations, Expenses: Takeda, Janssen Sonja ZweegmanConsulting or Advisory Role: Janssen-Cilag, Takeda, Celgene, Sanofi, OncopeptidesResearch Funding: Janssen-Cilag, Takeda, CelgeneTravel, Accommodations, Expenses: Janssen-Cilag, Takeda, CelgeneNo other potential conflicts of interest were reported. |
| سلسلة جزيئية: | NTR NTR6297 |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Boron Compounds) 4Z63YK6E0E (daratumumab) 71050168A2 (ixazomib) 7S5I7G3JQL (Dexamethasone) TE7660XO1C (Glycine) |
| تواريخ الأحداث: | Date Created: 20210504 Date Completed: 20211122 Latest Revision: 20211122 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1200/JCO.20.03143 |
| PMID: | 33945289 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.20.03143 |