scholarly journals Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up

Leukemia ◽  
2012 ◽  
Vol 26 (10) ◽  
pp. 2197-2203 ◽  
Author(s):  
R A Larson ◽  
A Hochhaus ◽  
T P Hughes ◽  
R E Clark ◽  
G Etienne ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Philadelphia Chromosome Positive

scholarly journals Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial

2018 ◽  
Vol 36 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Jorge E. Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Michael W. Deininger ◽  
Michael J. Mauro ◽  
Charles Chuah ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hazard Ratio ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment ◽  
Philadelphia Chromosome Positive

Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/ BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P < .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.

Efficacy of Frontline Nilotinib Therapy in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myeloid Leukemia in Early Chronic Phase (CML-CP)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 454-454 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Hagop M Kantarjian ◽  
Rajyalakshmi Luthra ◽  
Susan o'Brien ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
Elevated Transaminases

Abstract Abstract 454 Efficacy of Frontline Nilotinib Therapy in Patients (Pts) with Newly Diagnosed Philadelphia Chromosome (Ph)-Positive Chronic Myeloid Leukemia in Early Chronic Phase (CML-CP) Alfonso Quintás-Cardama, Hagop Kantarjian, Raja Luthra, Susan O'Brien, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, Guillermo Garcia-Manero, Stefan Faderl, Marina Konopleva, William Wierda, Elizabeth Burton, Jorge Cortes 1MD Anderson Cancer Center, University of Texas, Houston, TX Background: In 2005, we initiated a phase II study of nilotinib as 1st line therapy in pts with newly diagnosed CML-CP to investigate the efficacy and safety of nilotinib as frontline therapy for pts with CML-CP. Methods: The primary objective was to estimate the proportion of pts attaining major molecular response (MMR) at 12 months (mo). Pts with untreated CML-CP within 6 mo from diagnosis were eligible and received nilotinib 400 mg twice daily. Results: 100 pts (41% female) have received for a median of 24 mo (range 1 to 72mos). Median age was 49 years (range 17–86). Median WBC, PB blasts, PB basophils, hemoglobin, and platelet count was 42.6, 0%, 2.5%, 12.3, 307, respectively. Five pts (5%) had a variant Philadelphia chromosome and 1 (1%) had deletion of derivative chromosome 9. Seventy-two (72%), 20 (20%), and 8 (8%) pts had low, intermediate, and high Sokal risk score. Among the 102 CP pts who were not in CHR at the start, 100 (98%) achieved CHR (one discontinued after 2 weeks without adverse events). Among 73 CP pts followed for at least 12 mo, 69 (95%) achieved a complete cytogenetic response (CCyR). MMR at 18 mo has been achieved in 51 (89%) pts, including 30 (52%) with a complete molecular response (CMR)(Table 1). The median time to achieve CCyR, MMR was 6 mo each. Grade 3–4 thrombocytopenia, neutropenia, and anemia occurred in 9%, 12%, and 6% pts. The most frequent non-hematologic toxicities were rash (62%), pain (57%), and elevated transaminases (45%) and bilirubin (42%). However, grade 3–4 non-hematologic adverse events (possible, probable or suspected relationship only) were rare, including: pain and increased bilirubin (4% each), elevated lipase, fatigue, and elevated transaminases (2% each), and hyperglycemia (1%). One (1%) pt experienced QTc prolongation (grade 2; QTc prolonged from 444msec to 483msec), not associated with arrhythmias and resolved after a brief treatment interruption. Forty-five (45%) pts had transient treatment interruptions (median days off-nilotinib 7 [range 1–68]) and 27 (27%) had dose reductions. Of the patients that were dose reduced, their current or last known dose was either 200mg daily (n=7), 200mg twice daily (n=14), or 400mg daily (n=6). Nineteen (19%) pts terminated nilotinib therapy due to toxicity (n=7), personal reasons or loss to follow-up (n=7), loss of MCyR (n=2), progression to BP (n=2), or death (n=1). Of the pts who discontinued therapy, 3 were tested for BCR-ABL1 mutations; 2 were found to have mutations (F359C and Y253H). The 48 mo probability of EFS (event= loss of CHR, loss of MCyR, AP/BP, or death) is 88%. The annual rate of events during the first 48 mo of follow-up was 4%, 0%, 2%, 5%, and 0% and the rate of transformation 2%, 0%, 0%, and 0%, respectively. The best response achieved on nilotinib by the 2 pts that transformed to BP was CCyR and PCyR, respectively. The overall survival at 48 mos is 96%. One pt died due to stroke, unrelated to nilotinib. No other vascular events have been observed to date. Conclusion: Nilotinib 400 mg twice daily induces CCyR in 78% of pts as early as 3 mo and MMR in 86% at 12 mo after the start of therapy, with very low rates of progression to AP/BP and a mild toxicity profile. Disclosures: No relevant conflicts of interest to declare.

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