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

Abstract

Although long-term proteasome inhibitor therapy improves outcomes in multiple myeloma, many patients cannot tolerate long-term treatment or might require or prefer to continue treatment outside the hospital or clinic. The US MM-6 study is evaluating the in-class transition from parenteral bortezomib-to oral ixazomibbased therapy in routine clinical practice. Preliminary results indicate feasibility, prolonged therapy duration, promising efficacy, and treatment adherence and satisfaction. Background: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomibbased 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 nonetransplanteligible 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 progressionfree 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:

Duration of frontline therapy and impact on clinical outcomes in newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant

“…Another strategy utilized to extend DOT of 1LT is to employ in‐class transition (iCT) from a parenteral‐based induction to an all oral‐based regimen as demonstrated in the US MM‐6 trial. 33 Utilization of an all‐oral MM regimen has been reported by patients as a more convenient and preferred treatment approach, has decreased healthcare resource utilization and indirect costs, and maintained high rates of therapy adherence. 33 , 34 , 35 , 36 , 37 In addition to patient preference, transitioning patients to an all oral regimen may be beneficial in patients with decreased mobility or during times at which these immunocompromised patients may be at higher risk of contracting an infectious disease by reporting to healthcare settings—such as during the COVID‐19 pandemic.…”

“… 33 Utilization of an all‐oral MM regimen has been reported by patients as a more convenient and preferred treatment approach, has decreased healthcare resource utilization and indirect costs, and maintained high rates of therapy adherence. 33 , 34 , 35 , 36 , 37 In addition to patient preference, transitioning patients to an all oral regimen may be beneficial in patients with decreased mobility or during times at which these immunocompromised patients may be at higher risk of contracting an infectious disease by reporting to healthcare settings—such as during the COVID‐19 pandemic. Patient exposure could be minimized with decreased interruptions to ongoing therapy without compromising efficacy.…”

“…Another strategy utilized to extend DOT of 1LT is to employ in‐class transition (iCT) from a parenteral‐based induction to an all oral‐based regimen as demonstrated in the US MM‐6 trial 33 . Utilization of an all‐oral MM regimen has been reported by patients as a more convenient and preferred treatment approach, has decreased healthcare resource utilization and indirect costs, and maintained high rates of therapy adherence 33–37 .…”

Association of patient activity bio-profiles with health-related quality of life in patients with newly diagnosed multiple myeloma: a prospective observational cohort study

“…Current strategies on integrating digital health technology applications in the care of MM patients include digital health coaching and actigraphy during autologous stem cell transplantation, 7 , 8 artificial intelligence-based symptom monitoring, 9 and medication adherence when transitioning subcutaneous treatments to oral-based treatments. 10 To our knowledge, actigraphy has not yet been studied to evaluate physical activity trends in newly diagnosed symptomatic MM patients receiving induction chemotherapy as it correlates with HRQoL.…”

The MODIFY Study Protocol: An Open-Label, Single-Arm, Multicenter, Prospective Pragmatic Study of Ixazomib-Based Triple-Drug Therapy in Chinese Patients with Multiple Myeloma

“…Hence, frequent commuting between home and hospital is a burden for patients and their family. The feasibility of the in-class transition from a bortezomib-based induction to an all-oral ixazomib regimen has previously been demonstrated [ 20 ]. Overall good partial response (PR) rates and a tolerable safety profile make it possible to transition from a bortezomib-based induction regimen to an ixazomib-based triple-drug therapy in Chinese patients with MM.…”