CLL Coverage from Every Angle

Chemotherapy-Free, First-Line Regimens in CLL: Focus on Restricted Mean Survival Time

By: Jenna Carter, PhD
Posted: Tuesday, January 26, 2021

A Letter to the Editor published in Leukemia and Lymphoma reported findings from a network meta-analysis comparing chemotherapy-free treatments used for patients with untreated chronic lymphocytic leukemia (CLL). Due to some limitations with hazard ratios, the researchers reexamined the network data using the restricted mean survival time to assess progression-free survival in patients with the disease. Laura Bartoli, PhD, and Andrea Messori, PharmD, both of the Estar Toscana, HTA Unit, Toscana, Firenze Italy, examined the same six cohorts of the meta-analysis and found that using the restricted mean survival time yielded similar results as using hazard ratios.

“There is a growing literature that emphasizes important methodologic limitations of the hazard ratio, particularly when, in a survival study, there is no proof that the outcomes conform to the proportional hazards assumption. When this assumption is violated, the hazard ratio risks [can] be misleading, and preference should be given to another outcome measure: the restricted mean survival time,” stated Drs. Bartoli and Messori.

Over the course of 36 months, data from 6 cohorts were examined, and the restricted mean survival time was estimated using the ‘survRM2’ package after converting the Kaplan-Meier curves into individual patient data. Following estimations, the values were then ranked according to decreasing treatment efficacy.

Of the different treatment combinations assessed, the first three treatments—acalabrutinib plus obinutuzumab, venetoclax plus obinutuzumab, and ibrutinib plus obinutuzumab—were ranked as more effective than previously used combinations. Additionally, their findings confirmed previous results using hazard ratios.

“In our view, this confirmation is important for two reasons: First, this is one [of] the first comparisons made on the same clinical material between a narrative analysis based on [restricted mean survival time] and a network meta-analysis based on hazard ratio; second, since the hazard ratio has often been criticized in recent times, our confirmatory analysis strengthens the value of the results published elsewhere,” concluded the authors.

Disclosure: The authors reported no conflicts of interest.

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