Authored by Dr. Brian Koffman
Bottom Line:
There is a strong correlation between progression-free survival (PFS) and overall survival (OS) in relapsed / refractory (R/R) CLL / SLL. This is especially true in trials with target therapies, suggesting that, at least in those trials of R/R chronic lymphocytic leukemia / small lymphocytic lymphoma patients, PFS could be used as a quicker but still robust surrogate marker of OS.
Who Performed the Research and Where Was it Presented:
Dr. Vikalp Maheshwari from India led an international group of researchers in presenting this publication-only abstract at the European Hematology Association (EHA) Annual Congress in Madrid in 2024.
Background:
Due to the constantly improving therapies and better overall management of the disease and its complications, CLL / SLL patients are living longer. While that is great news, waiting to demonstrate a significant difference in mortality rates between two trial cohorts can take many years. The need to prove an overall survival advantage can cause significant delays in drug approval and higher costs in drug development, both leading to a possible chilling effect on new therapies becoming available. PFS has already been shown to correlate well with OS in frontline CLL trials, but there is less data on its value in R/R disease where its use could help speed up drug research.
Methods:
Reviews of three large medical research databases (Embase®, MEDLINE®, Cochrane) and conference proceedings (2021-2023) were conducted. To be included, randomized controlled trials (RCTs) had to report OS (time to death) and PFS (time to progression or death) in adult patients with R/R CLL / SLL receiving therapy.
Results:
- Twenty-five randomized controlled trials were included in the analysis of PFS as a surrogate marker for OS.
- The correlation between 6-month PFS and 12-month OS was 0.59 overall, but only 0.24 in the chemoimmunotherapy (CIT) subgroup. It was an impressive 0.87 in the Bruton’s Tyrosine Kinase inhibitor (BTKi) subgroup and identical to 0.87 in the BTKi and BCL2i subgroup (venetoclax is the only approved BCL2i, though others are in development).
- The correlation between 6-month PFS and 36-month OS was even higher, at 0.72 overall, but still a low 0.35 in the CIT subgroup. It was 0.84 in the BTKi subgroup and 0.88 in the BTKi and BCL2i subgroup.
Conclusions:
While the correlation between PFS and OS with CIT was not tight, the overall correlation was significant and positive. It was especially robust for targeted therapies, suggesting that PFS could be a reliable and valid surrogate marker for OS, at least in trials of targeted therapies. While OS should remain the gold standard, we are reassured that PFS should allow for more accelerated R/R CLL / SLL approvals, providing access to life-saving drugs sooner while confirmatory studies are pending.
Links:
Listen to Dr. Koffman’s monologue below.
Read the full EHA abstract at CORRELATION BETWEEN PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL AMONG PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA: A CLINICAL TRIAL-BASED APPROACH
