Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Low-Intensity and Chemo-Free Treatments in Ph+ ALL: Progression-Free Survival Based on Indirect Comparisons

Version 1 : Received: 29 June 2023 / Approved: 3 July 2023 / Online: 7 July 2023 (14:32:15 CEST)

How to cite: Rivano, M.; Mengato, D.; Chiumente, M.; Messori, A. Low-Intensity and Chemo-Free Treatments in Ph+ ALL: Progression-Free Survival Based on Indirect Comparisons. Preprints 2023, 2023070060. https://doi.org/10.20944/preprints202307.0060.v1 Rivano, M.; Mengato, D.; Chiumente, M.; Messori, A. Low-Intensity and Chemo-Free Treatments in Ph+ ALL: Progression-Free Survival Based on Indirect Comparisons. Preprints 2023, 2023070060. https://doi.org/10.20944/preprints202307.0060.v1

Abstract

: In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyse all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyse Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 562 reconstructed patients, 8 trials were analyzed. The survival data from these trials were pooled into three types of treatment: i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs associated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. In conclusion, the multi-treatment Kaplan-Meier graph generated in this study has effectively summarized the current evidence on these treatments in comparative terms.

Keywords

acute lymphoblastic leukemia; imatinib; ponatinib; dasatinib; nilotinib; blinatumomab; reduced-intensity chemotherapy; chemotherapy-free; progression-free

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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