Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study

Cancer Med. 2024 May;13(9):e7177. doi: 10.1002/cam4.7177.

Abstract

Objective: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens.

Methods: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity.

Results: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia.

Conclusion: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Keywords: duration of treatment; in‐class transition; proteasome inhibitor; real‐world community.

Publication types

  • Research Support, Non-U.S. Gov't
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Boron Compounds* / administration & dosage
  • Boron Compounds* / adverse effects
  • Boron Compounds* / therapeutic use
  • Bortezomib* / administration & dosage
  • Bortezomib* / adverse effects
  • Bortezomib* / therapeutic use
  • China
  • Female
  • Glycine* / administration & dosage
  • Glycine* / adverse effects
  • Glycine* / analogs & derivatives*
  • Glycine* / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Proteasome Inhibitors* / administration & dosage
  • Proteasome Inhibitors* / adverse effects
  • Proteasome Inhibitors* / therapeutic use
  • Retrospective Studies

Substances

  • ixazomib
  • Boron Compounds
  • Glycine
  • Proteasome Inhibitors
  • Bortezomib