Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myélodysplasies .
Lionel Ades,Thomas Prebet,Aspasia Stamatoullas,Christian Recher,Romain Guieze,Emmanuel Raffoux,Krimo Bouabdallah,Mathilde Hunault,Eric Wattel,Laure Stalnikiewicz,Andrea Toma,Hervé Dombret,Norbert Vey,Marie Sebert,Claude Gardin,Cendrine Chaffaut,Sylvie Chevret,Pierre Fenaux +17 more
TLDR
By comparison with conventional intensive chemotherapy, the treatment protocol used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies.Abstract:
Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m2/day, days 1-3 in cohort 1, escalated to 60 mg/m2/day, days 1-3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m2/day, days 1-7) and lenalidomide (10 mg/day, days 1-21 in cohorts 1 and 2, escalated to 25 mg/day, days 1-21 in cohort 3). Eighty-two patients with 5q deletion were enrolled, including 62 with acute myeloblastic leukemia, 62/79 (78%) of whom had a complex karyotype (median 7 cytogenetic abnormalities, all but 2 of them monosomal) and three had unknown karyotypes. Thirty-eight patients (46%) achieved complete remission and the overall response rate was 58.5%. Among the 62 patients with a complex karyotype, 27 achieved complete remission (44%) and 21 had cytogenetic responses. A lower response rate was observed in patients with acute myeloblastic leukemia but other pretreatment factors, including cytogenetic complexity and treatment cohort, did not significantly influence response. Fifteen patients underwent allogeneic stem cell transplantation, including 11 patients in first remission. The 1-year cumulative incidence of relapse was 64.6% and the median overall survival was 8.2 months. By comparison with conventional intensive chemotherapy, the treatment protocol we used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies. Clinical trial registry number: NCT00885508.read more
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Maintenance therapy in AML: The past, the present and the future.
TL;DR: Previous and ongoing approaches of maintenance therapy in AML are summarized, the most promising strategies are discussed, and ongoing and future studies including novel targeted therapies may demonstrate promising efficacy that could facilitate incorporation of maintenance Therapy into clinical practice.
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A decade of progress in myelodysplastic syndrome with chromosome 5q deletion.
TL;DR: Clinical and biological discoveries that have advanced the understanding of del(5q) MDS and its treatment since its approval by United States and European regulatory agencies are reviewed.
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Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs.
TL;DR: High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide.
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Immunomodulation with pomalidomide at early lymphocyte recovery after induction chemotherapy in newly diagnosed AML and high-risk MDS
Joshua F. Zeidner,Hanna A. Knaus,Hanna A. Knaus,Amer M. Zeidan,Amanda L. Blackford,Raul Montiel-Esparza,Hubert Hackl,Gabrielle T. Prince,Lukasz P. Gondek,Gabriel Ghiaur,Margaret M. Showel,Amy E. DeZern,Keith W. Pratz,B. Douglas Smith,Mark J. Levis,Steven D. Gore,Catherine C. Coombs,Matthew C. Foster,Howard Streicher,Judith E. Karp,Leo Luznik,Ivana Gojo +21 more
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