Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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: 7 September 2023 / Approved: 8 September 2023 / Online: 11 September 2023 (04:05:57 CEST)

A peer-reviewed article of this Preprint also exists.

Rivano, M.; Mengato, D.; Chiumente, M.; Messori, A. Low-Intensity and Chemo-Free Treatments in Ph+ ALL: Progression-Free Survival Based on Indirect Comparisons. Hematol. Rep. 2023, 15, 670-683. Rivano, M.; Mengato, D.; Chiumente, M.; Messori, A. Low-Intensity and Chemo-Free Treatments in Ph+ ALL: Progression-Free Survival Based on Indirect Comparisons. Hematol. Rep. 2023, 15, 670-683.

Abstract

In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has ac-cumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze 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 848 reconstructed patients, 9 trials were analyzed. The survival data from these trials were pooled into three types of treatments: i) treatments based on ty-rosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs as-sociated 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. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

Keywords

acute lymphoblastic leukemia; imatinib; dasatinib: nilotinib; ponatinib; blinatumomab; reducedintensity chemotherapy; chemotherapy-free; progression-free

Subject

Medicine and Pharmacology, Hematology

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