Shorter Time to Treatment Is Associated With Worse OS in Multiple Myeloma, Study Finds

Patients who received treatment for multiple myeloma (MM) within 7 days of diagnosis had worse overall survival (OS) outcomes than those who initiated therapy more than 30 days after diagnosis, according to a recent study published in Leukemia Research.

While MM remains incurable, treatment options for the plasma cell neoplasm have increased in recent years. Improvements in OS are due to novel therapy options and strategies, autologous stem cell transplantation, combination therapies, and better management of known complications. But in plasma cell abnormalities, it is not clear whether early treatment initiation is associated with OS benefits.

“The reasons for not having a clear understanding of prognostic impact of time to treatment initiation in MM can be attributed to current strict selection criteria that have created ineligible patients in clinical trials that are not reflective of the real diverse patient populations,” the authors wrote. Because individual patients in the real world differ from those in clinical trials, disparities in trial findings and real-world outcomes have been seen. Disease burden at diagnosis and overall patient health may also be closely linked to the amount of time between diagnosis and treatment initiation.

The study aimed to determine how time from diagnosis to treatment initiation impacts OS in a large, diverse population of patients with MM. A total of 38,178 patients with data in the National Cancer Database (NCDB) Participant-User File from 2004-2013 were included in the analysis, and the median follow-up was 27 months. All patients received systemic chemotherapy, and 3956 were excluded from logistic multivariate models in the study due to missing data in those covariates.

The average age at diagnosis was 67 years, and just over half (54%) of the patients were male. White patients comprised 75% of the study population, 21% of the population was Black, and 6% had Hispanic ethnicity. Most patients traveled less than 50 miles to receive treatment. The median time to therapy initiation was 17 days in the study, with 28% of the cohort receiving treatment within 7 days and 30% receiving treatment more than 30 days after diagnosis.

Patients who received systemic treatment less than 7 days after diagnosis had higher mortality overall than patients who started treatment more than 30 days post-diagnosis (hazard ratio, 1.52; P < 0.001). Two additional multivariate analyses separating patients with Charlson comorbidity scores of 0-1 from patients with scores of 2 or higher confirmed that time to treatment initiation was an independent prognostic factor.

In the multivariate analyses, mortality was also found to be higher in non-Hispanics, males, patients with higher Charlson scores, those with lower annual incomes, patients treated at a non-academic facility, individuals with Medicaid insurance, and those living less than 50 miles from treatment facilities. Factors associated with delayed time to treatment included Black race, female sex, lower Charlson comorbidity score, and higher education status.

A review of other studies was also conducted to provide additional insight, and results varied by cancer type.

“While time to initial treatment yielded varied outcomes in different malignancies, our study showed a better median OS in patients who started time to treatment > 30 days after diagnosis,” the authors wrote. “However, this should not be equated to specific therapy recommendation including an advocation for therapy delay in MM.”

The authors highlighted the fact that other factors may contribute to the higher mortality seen in patients who are treated faster, including sicker patients receiving more prompt treatment.

Another notable finding was that in the large NCDB cohort, the subgroup with the longest survival had a median OS of 46 months, which is significantly lower than the SWOG S0777 trial (NCT00644228) that reported a median OS of 75 months. While the study periods differed slightly, this finding suggests that exclusion criteria for clinical trials—such as comorbidities or high disease burden—might contributing factors to this disparity. Making clinical trials available to a wider range of patients may provide a better estimate of real-world outcomes.

“In our study, time to initiation of systemic therapy was an independent prognostic factor in MM,” the authors concluded. “Similar to other lymphoid malignancies, this metric may be a surrogate for high-risk disease in MM, and future trials may need to investigate time-to-treatment as a factor to allow enrollment of potentially sick patients.”

Reference

Hatic H, Inselman S, Inselman J, et al. Time to first treatment is an independent prognostic factor for multiple myeloma (MM). Leuk Res. Published online October 13, 2022. doi:10.1016/j.leukres.2022.106966