Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 7;11(8):2076.
doi: 10.3390/jcm11082076.

Old and New Drugs for Chronic Lymphocytic Leukemia: Lights and Shadows of Real-World Evidence

Monia Marchetti  1 , Candida Vitale  2 , Gian Matteo Rigolin  3   4 , Alessandra Vasile  5 , Andrea Visentin  6 , Lydia Scarfò  7 , Marta Coscia  2 , Antonio Cuneo  3   4
Affiliations
Review

Old and New Drugs for Chronic Lymphocytic Leukemia: Lights and Shadows of Real-World Evidence

Monia Marchetti et al. J Clin Med. .

Abstract

Several novel treatments for chronic lymphocytic leukemia (CLL) have been recently approved based on the results of randomized clinical trials. However, real-world evidence (RWE) is also requested before and after drug authorization in order to confirm safety and to provide data for health technology assessments. We conducted a scoping review of the available RWE for targeted treatments of CLL, namely ibrutinib, acalabrutinib, idelalisib, and venetoclax, as well as for chemoimmunotherapy (CIT). In particular, we searched studies published since 1 January 2010 and reported outcomes of the above treatments based on health databases, registries, or phase IV studies, including named-patient programs. We included both full papers and abstracts of studies presented at major meetings. Overall, 110 studies were selected and analyzed: 28,880 patients were treated with ibrutinib, 1424 with idelalisib, 751 with venetoclax, 496 with acalabrutinib, and 14,896 with CIT. Reported discontinuation rates were higher than in clinical trials, while effectiveness could not be indirectly compared with clinical trials since a detailed case mix, including cytogenetic risk factors, was partially available and propensity scores rarely applied. RWE on CLL can help to set realistic outcomes with novel treatments, however, real-world studies should be fostered, and available data shared.

Keywords: acalabrutinib; chronic lymphocytic leukemia; ibrutinib; idelalisib; real-world evidence; venetoclax.

PubMed Disclaimer

Conflict of interest statement

No conflict of interest to declare for A.V. M.M. received consultancy fees from Gilead srl and speaker fees from Amgen.

Figures

Figure 1
Figure 1
PRISMA diagram.* Reasons for exclusion: less than 20 patients (acalabrutinib), less than 50 patients (other series), mixed treatments, missing outcomes, review.
Figure 2
Figure 2
Publication trends of RWS. Distribution of the 433 retrieved RWS according to the year of publication.
See this image and copyright information in PMC

References

    1. Brugiatelli M., Bandini G., Barosi G., Lauria F., Liso V., Marchetti M., Mauro F.R., Meloni G., Zinzani P.L., Tura S., et al. Management of chronic lymphocytic leukemia: Practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Trans-plantation. Haematologica. 2006;91:1662–1673. - PubMed
    1. Mauro F.R., Bandini G., Barosi G., Billio A., Brugiatelli M., Cuneo A., Lauria F., Liso V., Marchetti M., Meloni G., et al. SIE, SIES, GITMO updated clinical recommendations for the management of chronic lymphocytic leukemia. Leuk. Res. 2012;36:459–466. doi: 10.1016/j.leukres.2011.08.013. - DOI - PubMed
    1. Cuneo A., Marchetti M., Barosi G., Billio A., Brugiatelli M., Ciolli S., Laurenti L., Mauro F.R., Molica S., Montillo M., et al. Appropriate use of bendamustine in first-line therapy of chronic lymphocytic leukemia. Recommendations from SIE, SIES, GITMO Group. Leuk. Res. 2014;38:1269–1277. doi: 10.1016/j.leukres.2014.06.017. - DOI - PubMed
    1. Collins R., Bowman L., Landray M., Peto R. The Magic of Randomization versus the Myth of Real-World Evidence. N. Engl. J. Med. 2020;382:674–678. doi: 10.1056/NEJMsb1901642. - DOI - PubMed
    1. Mwamburi M., Dalal H., Gala S. Trends in Research Using Observational Methodologies in Chronic Lymphocytic Leukemia (CLL): A Systematic Literature Review. Value Health. 2016;19:A760. doi: 10.1016/j.jval.2016.09.2361. - DOI