A recent study found that the majority of interventional phase 3 trials lacked a clear definition of high-risk multiple myeloma, and many patients were missing important data for risk stratification.
A study published in ejHaem found the majority of interventional phase 3 trials lacked a clear definition of high-risk multiple myeloma (HRMM) and that the definition of HRMM can vary significantly. The data emphasize a need for a consistent definition of HRMM, increased reporting, and trial designs that can help further define HRMM and improve MM treatment.
While long-term disease control is possible in MM, patients whose disease is considered high-risk typically have a poor prognosis and relapse or develop refractory disease early, according to the study authors. The revised International Staging System (R-ISS) is one system of risk stratification in MM, but disease parameters beyond those included in the R-ISS can be indicative of poor prognosis. Patient comorbidities also come into play when stratifying the risk of poor outcomes.
The study aimed to quantify the variability of definitions of HRMM and the frequency of reporting among phase 3 clinical trials in MM. “Identification of variability of HRMM definition is an important step toward a standardized definition that can ultimately help in better understanding of patients’ outcomes and in designing specific clinical trials focused on HRMM,” the authors wrote.
Data on the frequencies of MM cytogenetics reporting, the definitions of HRMM, staging criteria, the number of enrolled patients, trial start publication dates, sources of funding, and locations were collected from 271 interventional phase 3 MM trials in the ClinicalTrials.gov database.
Of the 271 trials included in the final analysis, 96 (35%) defined HRMM, and the cytogenics-based definition was used in 96% of those trials. Of 28 trials that began after the R-ISS was introduced in 2015, 4 used R-ISS criteria for risk stratification. A further 10 that started prior to the introduction of the R-ISS reported on it retrospectively. The original ISS was used in 50 of 79 trials that were conducted after 2005, and the R-ISS was used in 14 trials conducted after 2005.
In 66 trials that reported missing cytogenics data, a median of 22.6% of patients in each trial had cytogenics data missing. More recent trials trended toward less missing data. HRMM definition reporting was more common among studies that were peer-reviewed, those with a larger patient population, and in more recent studies.
“The findings of our study suggest that the definition of HRMM is underreported in interventional phase 3 MM trials,” the authors wrote. “Although almost all the trials that defined HRMM used a cytogenetics-based definition, a specific threshold and/or exact definitions were lacking. Such information is important as different high-risk cytogenetics aberrations can influence the disease progression and response to treatment differently.”
Considering the poor prognosis patients with HRMM face, the study emphasizes a need for a standard procedure for risk stratification and regular reporting among newly diagnosed patients with MM.
“The need for a unified definition, constant reporting, and ongoing innovative clinical trial designs attempting to define HRMM are crucial as this subset of patients requires individualized treatment options with the aim of improving upon their currently poor outcomes,” the authors concluded.
Abu Za'nouneh FJ, Ababneh O, Schinke C, et al. Variability of definition of high-risk multiple myeloma across phase III clinical trials. ejHaem. Published online March 28, 2023. doi:10.1002/jha2.675