All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma
Copyright © 2018. Published by Elsevier Ltd..
BACKGROUND: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance.
PATIENTS AND METHODS: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction.
RESULTS: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61-87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1-29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related).
CONCLUSIONS: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients.
TRIAL REGISTRATION NUMBER: NCT02046070.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:106 |
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| Enthalten in: |
European journal of cancer (Oxford, England : 1990) - 106(2019) vom: 30. Jan., Seite 89-98 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dimopoulos, Meletios A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.05.2020 Date Revised 05.05.2020 published: Print-Electronic ClinicalTrials.gov: NCT02046070 Citation Status MEDLINE |
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| doi: |
10.1016/j.ejca.2018.09.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM291030378 |
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| 100 | 1 | |a Dimopoulos, Meletios A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 04.05.2020 | ||
| 500 | |a Date Revised 05.05.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02046070 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018. Published by Elsevier Ltd. | ||
| 520 | |a BACKGROUND: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance | ||
| 520 | |a PATIENTS AND METHODS: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction | ||
| 520 | |a RESULTS: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61-87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1-29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related) | ||
| 520 | |a CONCLUSIONS: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT02046070 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Gruber, Astrid |e verfasserin |4 aut | |
| 700 | 1 | |a Hansson, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Neeraj |e verfasserin |4 aut | |
| 700 | 1 | |a Byrne, Catriona |e verfasserin |4 aut | |
| 700 | 1 | |a Labotka, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Teng, Zhaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Huyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Grzasko, Norbert |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Shaji |e verfasserin |4 aut | |
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