Comparable Efficacy and Safety of Chinese Generic Imatinib and Branded Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia: A Retrospective Study

Abstract

Objectives To compare the efficacy and safety of Chinese generic imatinib with branded imatinib in adults with newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). Methods Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei®, Hansoh, China; Genike®, Chiatai Tianqing, China) or branded imatinib (Glivec®, Novartis, Basel, Switzerland) between October 2013 and August 2018, during which both of the agents were commercially available in China, were retrospectively reviewed. Propensity score matching (PSM) case-control study was performed. Assessment of cytogenetic and molecular responses, failure-free survival (FFS), progression-free survival (PFS), and overall survival (OS) was according to European LeukemiaNet recommendation. Assessment of adverse events was according to Common Terminology Criteria for Adverse Events version 4.03. Cox regression model was used to identify independent factors associated with the responses and outcomes. Results In total, 442 adults receiving Chinese generic imatinib (n=236) or Glivec® (n=206) at an initial dose of 400mg once daily were included. 273 (61.6%) patients were male. Median age was 41 years (range, 18-83 years). Higher white blood cell (WBC) counts (P=0.019), rural household registration (P<0.001), lower education level (P<0.001), and divorced or widowed status (P=0.009) were more common in the Chinese generic imatinib cohort than those in the branded imatinib cohort. There was no significant difference in gender, age, Sokal risk, hemoglobin (HGB) level and basophile percentage in peripheral blood at diagnosis between the 2 cohorts. With the median follow-up of 30 months (range, 3-62 months) and 34 months (range, 3-67 months) in the generic and branded cohorts, respectively, there was no significant difference on the 4-year probabilities of achieving complete cytogenetic response (CCyR, 97% vs. 97.2%, P=0.851), major molecular response (MMR, 87.8% vs. 90.1%, P=0.131), molecular response 4.0 (MR4.0, 55.0% vs. 68.3%, P=0.169), molecular response 4.5 (MR4.5, 32.8% vs. 39.2%, P=0.191) as well as the 4-year probabilities of FFS (77.4% vs.81.1%, P=0.363), PFS (94.4% vs. 95.9%, P=0.480) and OS (95.8% vs. 98.3%, P=0.086) between the Chinese generic imatinib and Glivec cohorts. Multivariate analyses showed the type of drug was not associated with the cytogenetic and molecular responses and outcomes. However, male gender, education level, Sokal risk, WBC counts, HGB level and basophile percentage in peripheral blood at diagnosis were significantly associated with the responses or outcomes (Table 1). There was no significant difference on hematologic (P=0.923) and non-hematologic (P=0.655) adverse events between the 2 cohorts. After the PSM adjustment for gender, age, household registration, education level, marriage status, Sokal risk, WBC count and HGB level, 150 pairs of case-control patients with comparable baseline characteristics were re-analyzed. Similarly, multivariate analyses confirmed that Chinese generic or branded imatinib used as the front-line therapy was not associated with either responses or outcomes. Conclusions Socio-demographics might influenced patients' choice of the type of TKI used. Chinese generic imatinib and Glivec® as frontline therapy had comparable efficacy and safety in CML-CP patients. Disclosures No relevant conflicts of interest to declare.

Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia: A systematic review

“…Dasatinib. Three out of 46 pregnancies (6.5%) conceived under the effect of DAS ended up in elective termination or spontaneous abortion (the outcomes were not reported by TKI agents separately in one study [59]). One (2.3%) of 43 live births developed syndactyly [37]; otherwise, no malformations were reported.…”

“…Tables 1 and 2 show the summary of the studies included [10,11,. Seven papers were non-English language articles: one was written in Bulgarian [40], one in French [41], one in Japanese [61], and another four in Chinese [43,53,58,59]. We did not identify any comparative (controlled) studies: all evidence came from descriptive studies (case studies or case series studies).…”

“…No information is available on NIL, DAS, or BOS. We were unable to separate the outcomes of planned treatment discontinuation (four of 49 males) from those of no treatment discontinuation in one cohort of patients [59].…”

“…A total of 327 pregnancies conceived under the effect of IMA, 14 of which (4.3%) did not end up in live birth (six elective and seven spontaneous abortions, one stillbirth). The outcomes were not reported by TKI agents separately in one study [59].…”

“…Nilotinib. All pregnancies conceived under the effect of NIL ended up in live birth (the outcomes were not reported by TKI agents separately in one study [59]). Two (7.7%) of 26 pregnancies developed malformation; these were a case of pulmonary stenosis [32,47] and another case in which the malformation was not specified [56].…”