Feasibility of Long-term Proteasome Inhibition in Multiple Myeloma by in-class Transition From Bortezomib to Ixazomib

Abstract

Background: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral IRd (ixazomib-lenalidomide-dexamethasone) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence and duration while maintaining patients' health-related quality of life (HRQoL) and improving outcomes.

Patients and methods: US community sites are enrolling non-transplant-eligible patients with newly diagnosed multiple myeloma (MM) with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive IRd (up to 39 cycles or until progression or toxicity). The patients use mobile or wearable digital devices to collect actigraphy (activity and sleep) data and electronically complete HRQoL, treatment satisfaction and medication adherence questionnaires. The primary endpoint is progression-free survival. The key secondary endpoints include response rates and therapy duration.

Results: At the data cutoff, 84 patients had been treated (median age 73 years; 44% aged ≥ 75 years; 49% men; 15% Black or African American; and 10% Hispanic or Latino). Of the 84 patients, 62% were continuing therapy. The mean duration of total PI therapy was 10.1 months and for the IRd regimen was 7.3 months. With an 8-month median follow-up, the 12-month progression-free survival rate was 86% (95% confidence interval, 73%-93%) from both the start of bortezomib-based treatment and the start of IRd. The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after iCT. The IRd safety profile was consistent with previous clinical trial data, and HRQoL and treatment satisfaction were maintained.

Conclusion: The patients included in the US MM-6 study are representative of the real-world US MM population. The use of iCT might permit prolonged PI-based therapy with promising efficacy, without impacting patients' HRQoL or treatment satisfaction.

Keywords: Duration of treatment; Medication adherence; Oral therapy; Patient-reported outcomes; Real-world community.

Graphical abstract

Figure 1

Investigator-assessed Best Overall Responses After Bortezomib-based Induction and After an in-Class Transition (iCT) to IRd (Ixazomib, Lenalidomide, Dexamethasone). ∗Overall Response Rate (ORR) Included Complete Response (CR), Very Good Partial Response (VGPR), and Partial Resonse (PR). †CR Category Included Patients With a CR, Stringent CR, Immunophenotypic CR, or Molecular CR Abbreviations: CI = confidence interval; MR = minimal response; NE = not evaluable.

Figure 2

Patient-Reported Medication Adherence (Ixazomib, Lenalidomide, Dexamethasone) Over Time (Cycles 1-5). Patients Had Self-Reported Their Monthly Medication Adherence Using a Choice of Provided Categories (Excellent, Very Good, Good, Fair, or Poor) to Answer the Question “Thinking About the Past 4 Weeks, Please Rate Your Ability to Take Your Oral Cancer Medication as Prescribed?” After Cycle 5, the Number of Evaluable Patients Was < 30%. The Maximum Number of Cycles Received at the Data Cutoff Was 25 (n = 1). Patient-Reported Monthly Medication Adherence Data for the Previous 4 Weeks Were Available Through to Cycle 24 (n = 1). †Percentages Were Calculated According to the Number of Patients Who Had Reported Medication Adherence in Each Cycle

Figure 3

Electronic Patient-Reported Outcomes (ePROs) During Treatment With IRd (Ixazomib, Lenalidomide, Dexamethasone). (A) Mean Change From ePRO Baseline in European Organization for the Research and Treatment of Cancer (EORTC) Core Quality of Life (QoL) Questionnaire (QLQ-C30) Global Health Status/QoL Subscale Score (Items 29 and 30). (B) Mean Change From ePRO Baseline in EORTC QoL Questionnaire–Multiple Myeloma Module (QLQ-MY20) Item 43 (Peripheral Neuropathy). (C) Mean Change From ePRO Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM)-9 Subscale Scores. ∗ePRO Baseline Was Defined as Reported Measurement at End of Cycle 1 of IRd; Change From ePRO Baseline Was Only Calculated at Post-ePRO Baseline IRd Cycles for Which a Value Was Present and for Patients With an ePRO Baseline Value. †Data Were Available for up to 24 Cycles for Each Measure. Data Not Shown After Cycle 8 Because of Small Patient Numbers (n ≤ 10). Global Health Status/QoL Subscale Was Derived From Items 29 and 30 of the EORTC QLQ-C30 (Version 3). This Scale Has a Range of 0 to 100. Positive and Negative Changes Indicate an Improvement and Deterioration, Respectively, in QoL. EORTC QLQ-MY20 Item 43 (“Did You Have Tingling Hands or Feet?”) Measured the Burden of Peripheral Neuropathy Symptoms Using a Score Range of 1 to 4 (1, Not at All; 2, a Little; 3, Quite a Bit; and 4, Very Much). A Higher Score Indicates an Increase in Symptoms. The TSQM-9 Subscales (Effectiveness, Convenience, and Global Satisfaction) Have a Range of 0 to 100. Positive and Negative Changes Indicate an Increase and Decrease, Respectively, in Treatment Satisfaction