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Randomized Controlled Trial
. 2021 Sep;35(9):2517-2525.
doi: 10.1038/s41375-021-01148-x. Epub 2021 Feb 18.

Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial

Christoph Röllig #  1 , Hubert Serve #  2 , Richard Noppeney  3 , Maher Hanoun  3 , Utz Krug  4 , Claudia D Baldus  5 , Christian H Brandts  2 , Volker Kunzmann  6 , Hermann Einsele  6 , Alwin Krämer  7 , Carsten Müller-Tidow  7 , Kerstin Schäfer-Eckart  8 , Andreas Neubauer  9 , Andreas Burchert  9 , Aristoteles Giagounidis  10 , Stefan W Krause  11 , Andreas Mackensen  11 , Walter Aulitzky  12 , Regina Herbst  13 , Mathias Hänel  13 , Norbert Frickhofen  14 , Johannes Kullmer  15 , Ulrich Kaiser  16 , Alexander Kiani  17 , Hartmut Link  18 , Thomas Geer  19 , Albrecht Reichle  20 , Christian Junghanß  21 , Roland Repp  22 , Achim Meinhardt  23 , Heinz Dürk  24 , Ina-Maria Klut  25 , Martin Bornhäuser  26 , Markus Schaich  27 , Stefani Parmentier  27 , Martin Görner  28 , Christian Thiede  26 , Malte von Bonin  26 , Uwe Platzbecker  29 , Johannes Schetelig  26 , Michael Kramer  26 , Wolfgang E Berdel  30 , Gerhard Ehninger  26 ; Study Alliance Leukaemia (SAL)
Affiliations
Randomized Controlled Trial

Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial

Christoph Röllig et al. Leukemia. 2021 Sep.

Abstract

Early results of the randomized placebo-controlled SORAML trial showed that, in patients with newly diagnosed acute myeloid leukaemia (AML), sorafenib led to a significant improvement in event-free (EFS) and relapse-free survival (RFS). In order to describe second-line treatments and their implications on overall survival (OS), we performed a study after a median follow-up time of 78 months. Newly diagnosed fit AML patients aged ≤60 years received sorafenib (n = 134) or placebo (n = 133) in addition to standard chemotherapy and as maintenance treatment. The 5-year EFS was 41 versus 27% (HR 0.68; p = 0.011) and 5-year RFS was 53 versus 36% (HR 0.64; p = 0.035). Allogeneic stem cell transplantation (allo SCT) was performed in 88% of the relapsed patients. Four years after salvage allo SCT, the cumulative incidence of relapse was 54 versus 35%, and OS was 32 versus 50%. The 5-year OS from randomization in all study patients was 61 versus 53% (HR 0.82; p = 0.282). In conclusion, the addition of sorafenib to chemotherapy led to a significant prolongation of EFS and RFS. Although the OS benefit did not reach statistical significance, these results confirm the antileukaemic activity of sorafenib.

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Conflict of interest statement

GE and CR received institutional funding for the study from Bayer HealthCare Germany. All other authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. Survival outcomes based on randomization to the sorafenib arm (red line) or placebo arm (black line).
Event-free survival (A), relapse-free survival (B) and overall survival (C) with no censoring for allogeneic stem cell transplantation.
Fig. 2
Fig. 2. Treatment of patients after first relapse outside the SORAML trial.
CR complete remission, OS overall survival, SCT allogeneic stem cell transplantation, ident HLA-identical donor (10/10 matching alleles), haplo haploidentical donor (5/10 matching alleles).
Fig. 3
Fig. 3. Outcomes after salvage allo SCT after pretreatment with either sorafenib (red lines) or placebo (black lines) during first-line treatment.
Cumulative incidence of relapse (CIR, continuous lines) and non-relapse mortality (NRM, dashed lines).
Fig. 4
Fig. 4. Overall survival (OS) from the time of relapse.
Outcome for patients with pretreatment in the sorafenib arm (red line) or placebo arm (black line).
See this image and copyright information in PMC

References

    1. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–44. doi: 10.1038/nrd2130. - DOI - PubMed
    1. Klein M, Schermuly RT, Ellinghaus P, Milting H, Riedl B, Nikolova S, et al. Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling. Circulation. 2008;118:2081–90. doi: 10.1161/CIRCULATIONAHA.108.779751. - DOI - PubMed
    1. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006;98:326–34. doi: 10.1093/jnci/djj069. - DOI - PubMed
    1. Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X, et al. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst. 2008;100:184–98. doi: 10.1093/jnci/djm328. - DOI - PubMed
    1. Zhang W, Konopleva M, Ruvolo VR, McQueen T, Evans RL, Bornmann WG, et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia. 2008;22:808–18. doi: 10.1038/sj.leu.2405098. - DOI - PubMed

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