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Comparative Study
. 2024;47(9):430-433.
doi: 10.1159/000539391. Epub 2024 May 16.

A Multicentre, Randomized Trial in Adults with de novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia to Assess the Efficacy of Ponatinib versus Imatinib in Combination with Low-Intensity Chemotherapy, to Compare End of Therapy with Indication for Stem Cell Transplantation versus Tyrosine Kinase Inhibitor, Blinatumomab, and Chemotherapy in Optimal Responders, and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

Fabian Lang  1 , Heike Pfeifer  1 , Monika Brüggemann  2 , Eva Hermann  3 , Hubert Serve  1 , Nicola Goekbuget  1
Affiliations
Comparative Study

A Multicentre, Randomized Trial in Adults with de novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia to Assess the Efficacy of Ponatinib versus Imatinib in Combination with Low-Intensity Chemotherapy, to Compare End of Therapy with Indication for Stem Cell Transplantation versus Tyrosine Kinase Inhibitor, Blinatumomab, and Chemotherapy in Optimal Responders, and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

Fabian Lang et al. Oncol Res Treat. 2024.

Abstract

Introduction: Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL) is treated as standard of care (SoC) by imatinib-based treatment combined with induction and consolidation chemotherapy followed by allogeneic stem cell transplantation (SCT) in first remission. The German Multicenter ALL Study Group for Adult ALL (GMALL) reports about a trial to evaluate the impact of ponatinib-based therapy, blinatumomab treatment for suboptimal responders, and the possibility of omission of SoC Allo SCT in optimal responders entitled GMALL-EVOLVE.

Methods: Herein, imatinib is randomized versus ponatinib as frontline treatment combined with chemotherapy, optimal responders also get randomized between SCT and chemo-immunotherapy, and suboptimal responders receive immunotherapy before SCT. The trial is registered under the EudraCT number 2022-000760-21.

Conclusion: This trial will answer several major questions in the treatment of Ph+ALL.

Keywords: Acute lymphoblastic leukaemia; BCR:ABL1; Blinatumomab; Ponatinib.

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Conflict of interest statement

F.L. received consultancy and honoraria from Bristol Myers Squibb, Incyte, and Celgene; and consultancy, honoraria, and research funding from Novartis. N.G. received honoraria (advisory boards, invited talks) from Incyte, Amgen, Novartis, and Pfizer; institutional funding from Incyte, Amgen, and Pfizer. H.P. is a member of advisory board of Incyte; received research funding from Incyte; and received travel support and honoraria from Incyte. M.B. is contracted to carry out research for Affimed, Amgen, and Regeneron and is a member of the advisory boards of Amgen and Incyte and the speaker bureaus of Amgen, Janssen, Pfizer, and Roche. E.H. reported grants from DZHK (Grant from German Federal Ministry of Education and Research). H.S. received honoraria from Novartis, Robert Bosch Gesellschaft für Medizinische Forschung, Gilead Sciences; and consulting or advisory role from Gilead Sciences, IKP Stuttgart (Robert Bosch Gesellschaft für Medizinische Forschung).

Figures

Fig. 1.
Fig. 1.
Overview of study design. Description of the trial design illustrating interventional and observational part of trial phase. RI, randomization I; CONS I, consolidation I; MolNE, molecular response not evaluable; MolFail, molecular failure; MolCR, molecular complete remission; RII, randomization II; blina I, blinatumomab I; C 2, consolidation II; blina II, blinatumomab II; C 3, consolidation 3; blina III, blinatumomab III; C 4, consolidation 4; EOT-Soc, end of therapy-standard of care; SCT*, stem cell transplantation.
See this image and copyright information in PMC

References

    1. Gökbuget N, Hoelzer D. Treatment of adult acute lymphoblastic leukemia. Semin Hematol. 2009;46(1):64–75. - PubMed
    1. Gökbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120(9):1868–76. - PubMed
    1. Ottmann OG, Pfeifer H. First-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults. Curr Opin Oncol. 2009;21(Suppl 1):S43–6. - PubMed
    1. Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Rambaldi A, et al. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: final analysis of ALCANTARA study. Eur J Cancer. 2021;146:107–14. - PubMed
    1. Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al. Dasatinib-blinatumomab for ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020;383(17):1613–23. - PubMed

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