Efficacy and safety of generic imatinib compared to Glivec in chronic phase, chronic myeloid leukemia: A multicenter, observational study

ASH: 60th American Society of Hematology Annual Meeting & ExpositionKB Pagnano, C Fava, EC Miranda, I Bendit, FS Seguro, GHR Magalhaes, ND Clementino, M Conchon, NN Concalves, G Gaidano, M Lunghi, A Moellmann-Coelho, I Luise, M Bergamaschi, D Ferrero, R Centrone, P Pregno, L Fogliatto, V Giai, ME Dragani, E Moiraghi, J Bortolini, A Castelli, A Cuttica, TC Bortolheiro, C Pinna, CA De Souza, G Saglio | December 01, 2018

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Summary: Researchers conducted this study to assess the efficacy and safety of generic imatinib in patients with chronic phase, chronic myeloid leukemia (CP-CML) as first-line treatment. While many clinical trials have been focused on the use of Glivec, the proprietary branded form of imatinib, few have been done to prospectively evaluate the efficacy and safety of the generic formulation of imatinib. In this study, researchers found a higher rate of failure at 3 months in patients treated with generic imatinib and lower overall survival (OS), progression free survival (PFS) and event-free survival (EFS) at 24 months. Other between-group differences included a longer time to initiate treatment in the generic group, a higher proportion of patients with b2a2 transcripts (associated with an inferior rate of molecular responses and survival in other studies). The safety profile did not differ between the two groups. Longer follow-up is ongoing to assess long-term impacts on prognosis.

Methods:

  • In this multicenter, observational, cohort-type study, researchers included 160 patients treated with generic imatinib (mean age: 50 years) between January 2015 and September 2017; and 285 treated with Glivec between January 2010 and December 2011 (mean age: 54 years).
  • All patients started imatinib in CP less than 6 months from diagnosis, and were managed according to European Leukemia Net (ELN) 2009 and 2013 recommendations.
  • Researchers assessed adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.3, 2010, and measured EFS from treatment initiation until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated (AP) or blast crisis (BC) or death from any cause at any time during initial therapy or discontinuation of imatinib by any cause.
  • They measured OS from starting date of imatinib until to the date of death from any cause while on therapy or last seen, and PFS from starting date of imatinib to transformation to AP or BC or deaths while on therapy.

Results:

  • In the Glivec group, median follow-up was 25 months, and in the generic group, 11 months (P < 0.0001).
  • Median time between diagnosis and imatinib starting was 18 days vs 27 days, respectively (P=0.015).
  • Researchers found that Sokal score stratification in the Glivec and generic groups was as follows:
    • low risk 14.4% and 25.7% (respectively);
    • intermediate risk 42.3% and 38.2%; and
    • high risk 43.3% and 36.1% (P=0.02).
  • They found a b3a2 frequency of 51.5% in the Glivec group, compared with 37.7% in the generic group, and b2a2 of 41.4% vs 53.8%, respectively (P=0.017).
  • Researchers observed no significant difference in gender, Hasford, EUTOS scores and ECOG.
  • According to ELN 2013 criteria, rate of treatment failure at 3 months was 6.6% vs 14.7% in the Glivec and generic groups, respectively (P=0.04), but at 6 months, no significant differences remained (12.3% vs 18.9%; P=0.09).
  • Researchers also found no significant differences between groups in grade 3 and 4 hematological and non-hematological toxicity during the follow-up.
  • Progression occurred in five patients in the Glivec group, compared with three in the generic group.
  • Upon Cox regression multivariate analysis, researchers observed that the independent factors for EFS were age at diagnosis (HR: 1.03; 95% CI: 1.00-1.07; P=0.039) and toxicity grade 3-4 (HR: 3.37; 95% CI: 1.08-10.4; P=0.036).
  • Discontinuation of initial therapy occurred due to the following reasons in the Glivec and generic groups, respectively:
    • resistance (19.7% vs 47.5%),
    • intolerance (15.3% vs 23.7%),
    • non-adherence (4.4% vs 3.4%),
    • death (2.0% vs 6.8%),
    • clinical trial (0.5% vs 10.2%),
    • progression (2.0% vs 5.0%), and
    • pregnancy (0 vs 3.4%),
    • switch from Glivec to generic (56.1%).
  • At 24 months, researchers found higher OS in the Glivec compared with the generic group (99% vs 96%, respectively; P=0.016), higher PFS (98% vs 95%, P=0.026), and higher EFS (73% vs 58%; P < 0.0001).

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