Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors
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Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors. / Gambacorti-Passerini, Carlo; Kantarjian, Hagop M; Kim, Dong-Wook; Khoury, Hanna J; Turkina, Anna G; Brümmendorf, Tim H; Matczak, Ewa; Bardy-Bouxin, Nathalie; Shapiro, Mark; Turnbull, Kathleen; Leip, Eric; Cortes, Jorge E.
in: AM J HEMATOL, Jahrgang 90, Nr. 9, 09.09.2015, S. 755-68.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors
AU - Gambacorti-Passerini, Carlo
AU - Kantarjian, Hagop M
AU - Kim, Dong-Wook
AU - Khoury, Hanna J
AU - Turkina, Anna G
AU - Brümmendorf, Tim H
AU - Matczak, Ewa
AU - Bardy-Bouxin, Nathalie
AU - Shapiro, Mark
AU - Turnbull, Kathleen
AU - Leip, Eric
AU - Cortes, Jorge E
N1 - © 2015 Wiley Periodicals, Inc.
PY - 2015/9/9
Y1 - 2015/9/9
N2 - Long-term efficacy and safety of bosutinib (≥4 years follow-up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated-phase [AP, n = 79] chronic myeloid leukemia [CML], blast-phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1-88.6), 2.8 (0.03-55.9), 0.97 (0.3-89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan-Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib-related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge-to-transplant role in BP patients); toxicity was manageable.
AB - Long-term efficacy and safety of bosutinib (≥4 years follow-up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated-phase [AP, n = 79] chronic myeloid leukemia [CML], blast-phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1-88.6), 2.8 (0.03-55.9), 0.97 (0.3-89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan-Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib-related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge-to-transplant role in BP patients); toxicity was manageable.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aniline Compounds
KW - Antineoplastic Agents
KW - Benzamides
KW - Blast Crisis
KW - Diarrhea
KW - Drug Resistance, Neoplasm
KW - Female
KW - Fever
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Middle Aged
KW - Nitriles
KW - Piperazines
KW - Pneumonia
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - Protein Kinase Inhibitors
KW - Pyrimidines
KW - Quinolines
KW - Survival Analysis
KW - Treatment Outcome
U2 - 10.1002/ajh.24034
DO - 10.1002/ajh.24034
M3 - SCORING: Journal article
C2 - 26040495
VL - 90
SP - 755
EP - 768
JO - AM J HEMATOL
JF - AM J HEMATOL
SN - 0361-8609
IS - 9
ER -