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In Community-Based Study, Switching to Ixazomib in Newly Diagnosed MM Brought Improved Responses Across Age Groups


An analysis presented during the 64th American Society of Hematology Annual Meeting and Exposition showed that patients with multiple myeloma were able to experience improved responses to the proteasome inhibitor ixazomib after switching from bortezomib.

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

A subgroup analysis from US MM-6 (NCT03173092), presented in December 2022 during the 64th American Society of Hematology (ASH) Annual Meeting and Exposition 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 relating to poor tolerability and the burden of repeated, clinic-based treatment administration, particularly for older patients and those with comorbidities,” the investigators wrote.

According to the abstract, previously reported results showed that patients who received the regimen of ixazomib, lenalidomide, and dexamethasone (iRd) after bortezomib had improved clinical outcomes and maintained QOL. The new analysis presented at ASH examined the data by age group: those younger than 75 years and those 75 years and older.

The community-based setting for the study was key because moving patients out of a hospital clinic was seen as step toward improving QOL. Both the first author of the abstract, Ruemu E. Birhiray, MD, partner with Hematology-Oncology of Indiana in Indianapolis, and several coauthors practice 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; coauthors Robert M. Rifkin, MD, FACP, of Rocky Mountain Cancer Centers in Denver, Colorado; Christopher A. Yasenchak, MD, of Willamette Valley Cancer Institute and Research Center in Eugene, Oregon; and Roger M. Lyons, MD, FACP, of Texas Oncology in San Antonio, are all part of The US Oncology Network.

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

CHARACTERISTICS. Of the 140 patients receiving iRd as of February 28, 2022, 81 were younger than 75 years (58%) and 59 were 75 years or older (42%). For the younger group, the median age was 69 years (range 49-74); for the older group, the median age was 77 years (range 75-90). In the younger group, 60% were men, compared with 54% for the older group; 19% of the younger group were Black, compared with 17% for the older group; 11% of the younger group were Hispanic, compared with 5% for the older group; and 30% of the younger group had stage III disease, compared with 34% of the older group.

Among the patients enrolled, 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 iRd.

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

Treatment was stopped 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 due to other reasons in 35% of the younger group vs 38% of the older group.

With a median follow-up of 20 months, 22% of those 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 the younger patients and 95% of the 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 the serious events in each group considered treatment-related. Each age group had 2 on-study deaths. 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 AEs grade 3 or higher 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 drugs in 60%/16% in the younger patients and 58%/14% of the older patients.

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


1. Birhiray RE, Rifkin RM, Yasenchak CA, et al. In-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 analyses of the fully accrued dataset in patients aged < 75 and ≥ 75 years. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 3255. https://ash.confex.com/ash/2022/webprogram/Paper163071.html

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