Long-term progression-free survival in patients with chronic lymphocytic leukemia treated with novel agents: An analysis based on indirect comparisons.

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In chronic lymphocytic leukemia, growing evidence has accumulated about long-term outcomes of first-line treatments. Our objective was to perform indirect comparisons across first-line treatments. We applied the Shiny method, an artificial intelligence technique that analyses Kaplan-Meier curves and reconstructs patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and indirect head-to-head comparisons. The endpoint was progression-free survival (PFS). Seven first-line treatments were studied (1983 patients). Three treatments based on either ibrutinib or venetoclax (i.e., ibrutinib monotherapy, ibrutinib+ rituximab/obinutuzumab, and venetoclax+obinutuzumab) showed a very similar survival pattern. The PFS for these three treatments was significantly better than that of the remaining four treatments (fludarabine+cyclophosphamide+rituximab, chlorambucil+obinutuzumab, bendamustine+rituximab, and chlorambucil monotherapy). Regarding chlorambucil+ obinutuzumab, a significant between-trial variability was found. Long-term results are particularly favorable to ibrutinib (alone or in combination) and discourage further use of chlorambucil. As in other studies based on the Shiny method, the multi-treatment Kaplan-Meier graph summarized the available evidence in comparative terms. The evidence generated this way contributes to define the place in therapy of individual agents.