Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia: a landmark analysis

Jesus G. Berdeja, Michael Heinrich, Shaker R. Dakhil, Stuart L. Goldberg, Martha Wadleigh, Philip Kuriakose, Jorge Cortes, Jerald Radich, Bret Helton, David Rizzieri, Carole Paley, Ilva Dautaj, Michael J. Mauro

    Research output: Contribution to journalArticle

    Abstract

    ENESTnext (NCT01227577) was a single-arm, multicenter trial evaluating the rate of deep molecular response by 2 years in patients with newly diagnosed (within 6 months) chronic myeloid leukemia in chronic phase (CML-CP) treated with nilotinib 300 mg twice daily. Among 128 enrolled patients, 94 (73%) achieved major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1 IS ]) and 34 (27%) achieved confirmed MR 4.5 (BCR-ABL1 IS ≤0.0032% detectable or undetectable; primary endpoint) by 2 years. Three-month BCR-ABL1 levels were predictive of later responses. In exploratory analyses, digital polymerase chain reaction (PCR) detected BCR-ABL1 in 39.4% of samples from patients with confirmed MR 4.5 and identified further decreases in BCR-ABL1 with continued nilotinib. Safety results, including cardiovascular events, were consistent with those in other nilotinib trials. These results further substantiate the molecular response rates associated with frontline nilotinib therapy and demonstrate the feasibility of monitoring very low BCR-ABL1 transcript levels using digital PCR.

    Original languageEnglish (US)
    JournalLeukemia and Lymphoma
    DOIs
    StatePublished - Jan 1 2019

    Fingerprint

    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Polymerase Chain Reaction
    Leukemia, Myeloid, Chronic Phase
    Multicenter Studies
    Safety
    4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
    Therapeutics

    Keywords

    • BCR-ABL1
    • chronic myeloid leukemia
    • deep molecular response
    • digital PCR
    • nilotinib

    ASJC Scopus subject areas

    • Hematology
    • Oncology
    • Cancer Research

    Cite this

    Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia : a landmark analysis. / Berdeja, Jesus G.; Heinrich, Michael; Dakhil, Shaker R.; Goldberg, Stuart L.; Wadleigh, Martha; Kuriakose, Philip; Cortes, Jorge; Radich, Jerald; Helton, Bret; Rizzieri, David; Paley, Carole; Dautaj, Ilva; Mauro, Michael J.

    In: Leukemia and Lymphoma, 01.01.2019.

    Research output: Contribution to journalArticle

    Berdeja, JG, Heinrich, M, Dakhil, SR, Goldberg, SL, Wadleigh, M, Kuriakose, P, Cortes, J, Radich, J, Helton, B, Rizzieri, D, Paley, C, Dautaj, I & Mauro, MJ 2019, 'Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia: a landmark analysis', Leukemia and Lymphoma. https://doi.org/10.1080/10428194.2019.1590569
    Berdeja, Jesus G. ; Heinrich, Michael ; Dakhil, Shaker R. ; Goldberg, Stuart L. ; Wadleigh, Martha ; Kuriakose, Philip ; Cortes, Jorge ; Radich, Jerald ; Helton, Bret ; Rizzieri, David ; Paley, Carole ; Dautaj, Ilva ; Mauro, Michael J. / Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia : a landmark analysis. In: Leukemia and Lymphoma. 2019.
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    AU - Goldberg, Stuart L.

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