PS1046 FLT3 LIGAND PLASMA LEVELS HAVE NO IMPACT ON OUTCOMES AFTER ALLOTRANSPLANT IN ACUTE LEUKEMIA
Authors: P. Peterlin, J. Gaschet, T. Guillaume, A. Garnier, M. Eveillard, A. Le Bourgeois, M. Cherel, C. Debord, Y. Le Bris, O. Theisen, B. Mahe, V. Dubruille, C. Godon, N. Robillard, S. Wuillem, C. Touzeau, T. Gastinne, N. Blin, A. Lok, A. Bonnet, S. Le Gouill, P. Moreau, M.-C. Béné, P. Chevallier
Journal: HemaSphere (2019)

Background: Recent U.S. approval of GLAS+LDAC improved treatment options for patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is not an option due to older age or comorbidities. However, no clinical trials have directly tested glasdegib + low-dose cytarabine (GLAS+LDAC) against alternative AML therapies azacitidine (AZA) or decitabine (DEC). Number needed to treat (NNT) is a patient-centric measure familiar to clinicians: For overall survival (OS), NNT represents how many total patients need to receive one treatment over another in order to have one less death. Smaller NNT are desirable, with NNT = 1 indicating the greatest relative treatment effectiveness. Previously, indirect methods in NNT compared landmark endpoints (time-to-event) between different trials in oncology, including proportion alive at 24 months (24-month OS) (Guyot, Cheng, Tremblay et al, 2018). Aims: In this study, indirect NNT applied 12-month OS to estimate how many patients treated with GLAS+LDAC instead of AZA or DEC would result in one less death. Methods: Phase II GLAS+LDAC vs LDAC patient data (n = 116) were compared with separate published Phase III AZA vs LDAC (n = 312) and DEC vs LDAC (n = 485) OS results. Indirect NNT with 95% confidence intervals (CI) were derived from the absolute risk reduction (ARR) of death at 12-months (Casella and Berger, 2002). For reference, direct NNT were derived from within-trial ARR for each trial testing LDAC to GLAS+LDAC, AZA, or DEC (Sackett et al, 1996). Results: Within each trial, the direct NNT to prevent one patient death by 12-months was 3.23 (GLAS+LDAC vs LDAC), 6.90 (AZA vs LDAC) and 21.74 (DEC vs LDAC). With indirect NNT, for every three patients treated with GLAS+LDAC rather than AZA, one less would have died (NNT = −3.33). Likewise, for every two patients treated with GLAS+LDAC vs DEC, one less would have died (NNT = −2.45). Results with 95% CI conveyed statistical superiority of GLAS+LDAC vs AZA or DEC (Table 1). Table 1. Within-trial and Indirect NNT Results for AML Treatments∗12-month OS for DEC vs LDAC was estimated from published Kaplan-Meier graphs (pooled 28 Supportive Care patients with 215 LDAC patients). ∗∗Negative values indicated benefit with GLAS+LDAC. In the text, absolute values were reported to aid interpretation. Summary/Conclusion: Indirect NNT of 12-month OS demonstrated statistically significant findings for use of GLAS+LDAC over AZA or DEC. These results coincide with previously published Bucher indirect comparisons of GLAS+LDAC vs AZA or DEC (OS hazard ratios). With challenges in clinical trial representation of smaller populations, including older AML patients with comorbidities, indirect comparisons can be supportive of informative clinical decision-making and treatment prioritization.