The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Switching patients with transplant-ineligible multiple myeloma from a regimen containing parenterally administered bortezomib to an all oral regimen consisting of ixazomib in combination with lenalidomide and dexamethasone (IRd) did not appear to negatively affect rates of progression-free survival (PFS) or quality of life (QoL), according to early results from a phase 4 clinical trial presented during the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.1

Bortezomib and ixazomib facilitate cell death through interference with the breakdown of waste proteins, and are approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma. These proteasome inhibitors are also included as recommended options for the treatment of patients with non-transplant eligible multiple myeloma in the National Comprehensive Cancer Network treatment regimens.2-4 However, while bortezomib is administered through subcutaneous or intravenous injection, ixazomib is an oral agent. Hence, it is possible that long-term administration of proteasome-based therapy would be facilitated through the use of an all oral regimen in this setting.

This multicenter, single-arm, open-label study (US MM-6; Clinical Trials.gov Identifier: NCT03173092) was designed to evaluate the efficacy and safety, as well as QoL and treatment adherence, after switching from a bortezomib-based regimen to IRd in a real-world, community-based setting. Study inclusion criteria included transplant ineligibility or transplant delayed status for over 2 years, and induction therapy with 3 cycles of a bortezomib-containing regimen without evidence of progressive disease. QoL was assessed using 2 validated assessment measures, and rest/activity cycles were measured with mobile and digital devices. The primary study endpoint was 2-year PFS, and secondary study endpoints included rates of complete response (CR), very good partial response (VGPR), and partial response (PR), as well as duration of therapy.

Of the first 84 patients enrolled in the study who were included in this analysis, the median age was 73 years and 15% of patients identified as black or African American, and approximately one-third of patients classified as having stage III disease according to the International Staging System. This group of patients had high rates of comorbidities at baseline, including hypertension (57%), anemia (44%), fatigue (43%), renal/urinary disorders (40%), cardiac disorders (30%), insomnia (30%), and peripheral neuropathy (13%). Most patients (85%) received bortezomib, lenalidomide, and dexamethasone (VRd) as induction therapy.


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In this ongoing study, the mean duration of proteasome inhibitor therapy from the start of induction therapy was 10.1 months with the mean duration of IRd of 7.3 months. Furthermore, at data cut-off, 62% of patients were continuing to receive study drugs.

The overall response rate (ORR) following bortezomib-induction therapy was 62% compared with an ORR of 70% following initiation of IRd, although the rates of CR were 4% and 26% following bortezomib-based induction therapy and IRd, respectively.

At a median follow-up of 8 months, the 12-month PFS rate was 86% from initiation of bortezomib-based therapy and the start of treatment with IRd, however these data were immature at the time the interim analysis was performed.

Regarding safety, no unexpected safety signals were observed, with grade 3 or higher treatment-emergent adverse events (TEAEs) reported in 48% of patients, and serious TEAEs in 36% of patients. Rates of grade 3 diarrhea, pneumonia, syncope, and anemia were 7%, 6%, 6%, and 5%, respectively. Seven percent of patients discontinued study drug due to TEAEs. Two patient deaths occurred on study, with 1 death attributed to nontreatment related end-stage renal disease and the other due to treatment-related pneumonia.

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Mean sleep duration according to actigraphy was 7.90 hours/day. Patient-reported QoL and treatment satisfaction measures did not show significant changes over time compared with baseline assessments following the first cycle of IRd.

In his concluding remarks, the presenting author, Sudhir Manda, MD, from Arizona Oncology U.S./Oncology Research in Tucson, noted that “the current data show that an in-class transition to an oral proteasome inhibitor may permit prolonged [proteasome inhibitor]-based therapy with promising efficacy without impacting patients’ QoL.”

Disclosures: Funding for this study was provided by Millennium Pharmaceuticals, Inc. which was acquired by Takeda Pharmaceutical Co. Ltd. Please refer to reference for a complete list of authors’ disclosures.

Read more of Cancer Therapy Advisor‘s coverage of the EHA virtual meeting by visiting the conference page.

References 

  1. Manda S, Yimer HA, Girnius SK, et al. Long-term proteasome inhibitor in multiple myeloma (MM) following an in-class transition from bortezomib (BTZ) to ixazomib (IXA): Updated real-world (RW) data from the US MM-6 community-based study. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S332.
  2. National Comprehensive Cancer Network (NCCN) Multiple Myeloma Guidelines. V4.2020. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Published May 8, 2020. Accessed June 10, 2020
  3. Ixazomib (Ninlaro) [package insert]. Cambridge, MA: Takeda Pharmaceutical Co Ltd.; 2020. Accessed
  4. Bortezomib (Velcade) [package insert]. Cambridge, MA: Millennium Pharmaceuticals Inc.; 2019.