In a community-based study, switching to ixazomib in newly diagnosed MM resulted in better responses across all age groups

Patients younger than 75 years with newly diagnosed multiple myeloma improved responses after transitioning from bortezomib-based therapy to an all-oral regimen of ixazomib (Ninlaro), lenalidomide (Revlimid), and dexamethasone without impairing quality of life (QOL ), according to the results of a community-based study.

A subgroup analysis of US MM-6 (NCT03173092), presented in December 2022 during the 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) in New Orleans, Louisiana, showed that, regardless of age, patients with MM were able to experience improved responses to the proteasome inhibitor ixazomib after switching from bortezomib (Velcade) after 3 cycles.1

“Achieving prolonged therapy with parenteral proteasome inhibitors (PI) in MM can be challenging in routine practice due to issues related to poor tolerability and the burden of repeated administration of clinically based treatment, particularly for older patients and those with comorbidities,” the researchers wrote.

Per the abstract, previously reported results showed that patients who received the ixazomib, lenalidomide, and dexamethasone (iRd) regimen after bortezomib improved clinical outcomes and maintained quality of life. The new analysis presented at ASH looked at the data by age group: under-75s and over-75s.

The community-based environment for the study was critical because removing patients from a hospital clinic was seen as a step towards improving quality of life. Abstract first author Ruemu E. Birhiray, MD, partner of Hematology-Oncology of Indiana in Indianapolis, and several co-authors work with leading community oncology networks that are Strategic Alliance Partners of The American Journal of Managed Care®. Hematology Oncology of Indiana is part of the American Oncology Network; co-authors Robert M. Rifkin, MD, FACP, of Rocky Mountain Cancer Centers in Denver, Colorado; Christopher A. Yasenchak, MD, of the Willamette Valley Cancer Institute and Research Center in Eugene, Oregon; and Roger M. Lyons, MD, FACP, of Texas Oncology in San Antonio, are part of The US Oncology Network.

Patients were enrolled at community centers to receive iRd for up to 39 cycles or until disease progression or toxicity. Major secondary endpoints included partial, very good partial, and complete response rates; and duration of therapy (DOT).

FEATURES. Of the 140 patients who received iRd on Feb 28, 2022, 81 were younger than 75 years old (58%) and 59 were 75 years old or older (42%). For the youngest group, the median age was 69 years (range 49-74); for the oldest group, the median age was 77 years (range 75-90). In the younger group, 60% were men, compared to 54% in the older group; 19% of the younger group were black, compared with 17% of the older group; 11% of the younger group was Hispanic, compared with 5% of the older group; and 30% of the younger group had stage III disease, compared with 34% of the older group.

Among enrolled patients, 47% of the younger group had lytic bone disease, compared with 44% of the older group; 91% of the younger group and 97% of the older group had at least 1 comorbidity at the start of the iRd.

RESULTS. The overall response rate increased from 60% at the end of bortezomib induction to 79% after transition to iRd in patients younger than 75 years; increased from 64% to 76% in those aged 75 and over.

Treatment was discontinued due to progressive disease in 20% of the younger group vs 19% of the older group; due to adverse events (AEs) in 29% of the younger group vs 17% of the older group; and for other reasons in 35% of the younger group vs 38% of the older group.

With a median follow-up of 20 months, 22% of people in the younger group and 17% in the older group were still on study treatment. Median DOT was 11.8 months and 8.5 months for iRd, respectively, and 14.8 months and 11.1 months for total PI-based therapy.

ADVERSE EVENTS. Treatment-emergent AEs were seen in 98% of younger patients and 95% of older patients, of which 81% and 75% were considered treatment-related, respectively. Serious treatment-emergent AEs were seen in 41% and 47% of the respective groups, with 14% of serious events in each group considered treatment-related. Each age group had 2 deaths in the study. The most common treatment-emergent AEs were diarrhea (47% and 49% in the younger and older groups), peripheral neuropathy not otherwise classified (43% and 34%, respectively), and fatigue (36% and 31%). The most common grade 3 or higher AEs in younger patients were diarrhea (7%), neutropenia (6%), anemia (6%) and decreased platelets (6%). Among older patients, the most common grade 3 or higher AEs were diarrhea (10%), pneumonia (8%) and hypokalemia (7%). AEs led to modification/discontinuation of any of the 3 medications in 60%/16% of younger patients and 58%/14% of older patients.

QUALITY OF LIFE. “Patient-reported quality of life was assessed using questionnaires that patients completed electronically, and activity and sleep levels were measured using wearable digital devices,” explained Birhiray in the presentation. Overall, the EORTC-QLQ-C30 Global Health QOL Score was maintained in both groups, with daily activity and sleep hours generally maintained.


1. Birhiray RE, Rifkin RM, Yasenchak CA, et al. Class transition (iCT) from parenteral bortezomib to oral ixazomib therapy in newly diagnosed multiple myeloma (NDMM) in patients from the community-based US MM-6 study: subgroup analyzes of the fully cumulative dataset in patients aged < 75 and ≥ 75 years. Presented at: 64th Annual Meeting and Exposition of the American Society of Hematology; December 10th to 13th, 2022; New Orleans, LA. Summary 3255.

In a community-based study, switching to ixazomib in newly diagnosed MM resulted in better responses across all age groups

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