Real-world data give us great opportunities to answer questions that clinical trials are not addressing. For example, real-world data can identify toxicities and adverse events that were previously not seen or discovered in clinical trials. Historically, real-world studies have offered comparative insights on questions related to ibrutinib vs idelalisib, evaluated high-risk populations, investigated whether there was a role for CD20 antibodies in combination with venetoclax, and offered information about treatment sequencing. Such information guides how we make decisions about multiple lines of therapy.

At ASH 2021, abstract 4078 provided data from the Flatiron Health database that reproduced findings that are relevant to prognostic testing and practice patterns, confirming previously published results from the Connect CLL and informCLL registries. There is a disconnect between guideline recommendations on prognostic testing and practice patterns in the real world. The results from published studies indicate that many patients are either not having the appropriate testing performed prior to the selection of first-line therapy or they are receiving chemoimmunotherapy inappropriately (eg, a feature that is associated with suboptimal outcomes with chemoimmunotherapy is, at some point, identified). This illustrates the disconnect between the recommendations on when to perform prognostic testing and the actual real-world performance of testing, and it also suggests a disconnect in the interpretation of the results to guide treatment decision making. These findings highlight the need to ensure that everyone is on the same page with regard to deciding which tests should be performed, interpreting test results, and determining how those tests should inform treatment decisions. We need to be in agreement before we take additional steps toward even more sophisticated prognostication.

There are likely many factors that might explain these observations, but there is no way to have good insight into these patterns without exploring them further. The solution lies in working with clinicians to better understand the problem and then addressing these gaps individually. We should also continue to conduct real-world evaluations of testing and treatment patterns and to present these types of findings at meetings where the clinicians in attendance are the individuals who may benefit the most.