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All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma

Dimopoulos, Meletios A.; Grosicki, Sebastian; Jędrzejczak, Wiesław W.; Nahi, Hareth; Gruber, Astrid; Hansson, Markus LU ; Gupta, Neeraj; Byrne, Catriona; Labotka, Richard and Teng, Zhaoyang, et al. (2019) In European Journal of Cancer 106. p.89-98
Abstract

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) +... (More)

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.

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published
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keywords
Elderly, Multiple myeloma, Newly diagnosed, Oral therapy, Transplant-ineligible
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European Journal of Cancer
volume
106
pages
10 pages
publisher
IFAC & Elsevier Ltd.
external identifiers
  • scopus:85056777478
ISSN
0959-8049
DOI
10.1016/j.ejca.2018.09.011
language
English
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yes
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54dfce61-3cb2-4f6f-9051-bc873dc2629e
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2018-11-29 11:59:09
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2019-03-12 04:18:37
@article{54dfce61-3cb2-4f6f-9051-bc873dc2629e,
  abstract     = {<p>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/m<sup>2</sup> 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.</p>},
  author       = {Dimopoulos, Meletios A. and Grosicki, Sebastian and Jędrzejczak, Wiesław W. and Nahi, Hareth and Gruber, Astrid and Hansson, Markus and Gupta, Neeraj and Byrne, Catriona and Labotka, Richard and Teng, Zhaoyang and Yang, Huyuan and Grzasko, Norbert and Kumar, Shaji},
  issn         = {0959-8049},
  keyword      = {Elderly,Multiple myeloma,Newly diagnosed,Oral therapy,Transplant-ineligible},
  language     = {eng},
  pages        = {89--98},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma},
  url          = {http://dx.doi.org/10.1016/j.ejca.2018.09.011},
  volume       = {106},
  year         = {2019},
}