Real-world Evidence Details Use of Ixazomib as Maintenance Therapy for MM

Real-world data on the efficacy and safety of oral Ninlaro (ixazomib) -based maintenance therapy revealed the treatment is a favorable option for long-term administration among patients with multiple myeloma (MM) not undergoing transplantation. Findings were published in Cancer Medicine.

Patients with MM have a median survival of at least 10 years, and despite improvements in prognosis, almost all patients will eventually relapse, authors explained. “The paradigm of long-term therapy in MM has been widely accepted, since continuous or maintenance therapy after plateau demonstrated obvious prolonged disease control,” they added.

Ixazomib is an oral proteasome inhibitor (PI) approved for patients who have received at least 1 previous therapy for MM. To retrospectively evaluate the treatment in patients who plateaued after bortezomib-based regimens, researchers assessed real-world data collected from a single institution in China.

A total of 71 patients with newly diagnosed MM (NDMM; n = 37) or relapsing/remitting MM (RRMM; n = 34) were consecutively observed after plateauing between April 2018 and April 2020. All individuals received at least 2 cycles of ixazomib within 60 days of the completion of the induction therapy, researchers wrote.

Median patient age was 63 (IQR 41-80) and the majority of patients were male (60.6%). In addition, all patients received a median of 9 cycles of bortezomib (IQR 6-14; induction phase) and a median of 6 cycles of ixazomib (IQR 2-25; maintenance phase) for a median follow-up time of 26.5 months (IQR 7.1-56.8).

Analyses revealed:

• The overall response rate (ORR) was 81.7%, including 34 patients (47.9%) with a very good response rate or better (≥VGPR) after induction therapy
• The ORR was transformed to 74.6% including 39 patients of ≥VGPR (54.9%) after maintenance therapy
• Of these, 18 patients (25.4%) exhibited deepened responses
• With 26.5 months median follow-up, median progression-free survival (PFS) was 28.4 and 16.5 months from the start of bortezomib and 16.2 and 10.0 months from the initiation of ixazomib in the NDMM and RRMM groups, respectively
• Responses deepened during the maintenance phase (hazard ratio [HR], 0.270; P =.007), and responses of ≥VGPR during the induction phase (HR, 0.218; P < .001) were confirmed to independently predict longer PFS after multivariate analyses
• Severe adverse events (AE) (grade 3/4) were relatively rare
• Bortezomib-emergent peripheral neuritis (PN) was significantly relived after the transition to ixazomib (P < .001)

Individual preference was the most frequent reason for discontinuation reported and no AE-associated permanent drug interruptions or deaths were recorded. At the latest follow-up, 12 patients had died of progressive disease (PD) from the RRMM cohort and 5 died of non-PD from the NDMM cohort, researchers said.

“With deepening responses but worsening PN, the ixazomib-based regimen exhibited a good therapeutic efficacy with feasible tolerance,” they wrote. “In addition, responses deepened during maintenance and ≥VGPR during induction have demonstrated the association with prolongation of PFS.”

The population studied in this real-world analysis was older, has worse Eastern Cooperative Oncology Group (ECOG) performance and more terminal renal function compared with populations included in clinical trials.

However, the relatively small number of patients recruited from a single institution mark limitations to the study and future multi-center and larger prospective studies are warranted to verify results.

Overall, the oral weekly regimen examined in this study may offer more flexibility to patients with MM and serve as a more convenient alternative to injectable therapies, authors concluded.

Reference

Shen M, Zhang J, Tang R, et al. Ixazomib-based maintenance therapy after bortezomib-based induction in patients with multiple myeloma not undergoing transplantation: A real-world study. Cancer Med. Published online October 16, 2021. doi:10.1002/cam4.4313