Ixazomib Plus Lenalidomide and Dexamethasone Is Effective in Routine Practice for R/R Multiple Myeloma

Data on the use of ixazomib plus lenalidomide/dexamethasone were similar to results from the pivotal TOURMALINE-MM1 trial, suggesting patients with multiple myeloma in routine practice could achieve similar outcomes to patients treated on clinical trials.

The combination of ixazomib (Ninlaro) plus lenalidomide (Revlimid) and dexamethasone (IRd) to treat patients with relapsed/refractory multiple myeloma (RRMM) in routine clinical practice produced efficacy and safety data similar to that from the pivotal TOURMALINE-MM1 trial (NCT01564537), according to research published in Future Oncology.1

The pooled analysis from the observational INSIGHT-MM study (NCT02761187) and the Czech Registry of Monoclonal Gammopathies (RMG) suggests that patients in the real-world setting undergoing treatment, who typically have different baseline characteristics than patients on clinical trials, can achieve similar benefits with therapy.

“These real-world data suggest that IRd provides a greater benefit to patients with RRMM when given in earlier (second or third) versus later lines of therapy,” wrote the investigators. “The data also suggest that IRd is well tolerated by patients when used in routine clinical practice, including older patients and those with advanced disease and/or multiple comorbidities, with no new safety signals.”

A total of 263 patients were analyzed at the data cutoff point, with 132 patients from INSIGHT MM and 131 from the Czech RMG. The patient population had a median of 2 prior lines of therapy, and the median time from diagnosis to the start of IRd was 35.8 months. Median duration of follow-up was 14.8 months.

The overall response rate (ORR) was 73% for all patients as well as for the INSIGHT MM (n = 52) and the Czech RMG (n = 84) groups individually. More, the median time to best response for patients in the INSIGHT MM group was 3.4 months (range, 0.7-15.2), while the median time to first response was 1.2 months (range, 0.2-16.9) for patients in the Czech RMG group.

Further results showed the median duration of IRd therapy was 11.8 months (95% CI, 9.4-14.5), the median progression-free survival was 21.2 months (95% CI, 15.2-25.9) and the median time-to-next therapy was recorded at 33.0 months (95% CI, 26.2-47.4). Median overall survival was not reached.

In terms of the safety profile, 17% and 36% of patients treated with IRd required dose reductions of ixazomib and lenalidomide, respectively. More, 10% of patients needed dose reductions of ixazomib due to the adverse events (AEs) experienced. The common AEs that led to these reductions included diarrhea, neutropenia, thrombocytopenia, and neuropathy (2% of patients for each AE).

For lenalidomide, 23% of patients required dose reductions, with the most common AEs leading to these events including neutropenia (7%), thrombocytopenia (5%), and fatigue and diarrhea (3% each).

“In addition to offering a tolerable treatment option, the all-oral IRd regimen could also represent a convenient treatment approach for patients who may find it difficult to access infusion centers or who do not want to travel to a hospital or clinical setting to receive treatment, which is critically important during the current COVID-19 pandemic,” wrote the investigators. “Therefore, IRd therapy offers the potential for improved medication adherence compared with regimens which include a parenteral component.”

Due to the limited maturity of these data, conclusions drawn from the research should be considered with caution. Another limitation of the research deals with the high number of patients with missing response data. The investigative team lists a number of factors that could have contributed to the missing information, including quarterly data collection procedures and the lack of a standard process when interpreting the response assessments for documentation, among other things.

The phase 3 TOURMALINE-MM1 trial led to the approval of the combination in the indicated patient population in 2015.2

Reference:

1. Hajek R, Minarik J, Straub J, et al. Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. Future Oncol. March 26, 2021. doi: 10.2217/fon-2020-1225

2. U.S. FDA Approves Takeda’s NINLARO® (ixazomib), the First and Only Oral Proteasome Inhibitor to Treat Multiple Myeloma. News release. Takeda Pharmaceutical Company Limited. November 20, 2015. Accessed April 23, 2021. https://bit.ly/3azs8VE