Are Generic Imatinib Formulations Really as Effective as Originial Imatinib in Chronic Myeloid Leukemia: Real Life Data

Abstract

Abstract Introduction and Aim: Generic imatinib formulations are increasingly being used as more affordable alternatives worldwide and a few studies have evaluated the safety and efficacy of these. We have retrospectively analyzed our chronic-phase chronic myeloid leukemia (CP- CML) cohort in terms of first-line treatment with Glivec versus generic imatinib. This study aims to evaluate the safety and efficacy of generic imatinib products in CP- CML as the first-line treatment. Material and Method: We retrospectively analyzed our CP- CML cohort from January 2000 to December 2020 treated with either Glivec or one of the generic imatinib formulations. All our patients were followed in accordance with European Leukemia Net (ELN) 2020 recommendations and national hematology association CML guidelines and response definitions were applied according to ELN 2020 criteria. Event-free survival (EFS) was defined as the time between treatment initiation and either loss of hematological response, progression to accelerated phase (AP) or blastic phase (BP), or an adverse effect severer than grade 1. Overall survival (OS) was defined as the time between treatment initiation and death, while on imatinib. For statistical analyses, SPSS version 21.0 was used. All p values < 0.05 were considered statistically significant. Results: A total of 307 patients were analyzed comparing 186 (60.6 %) patients on Glivec (original imatinib) with 121 patients on (39.4 %) generic formulations. 146 (47.6 %) were females. The median age was 46 years (18-88) for Glivec and 51 years (20-79 years) for the generics group (p=0.01). Risk stratifications according to Sokal, Hasford, and ELTS scores were run for both Glivec and generic formulation groups. There was no statistically significant difference in the gender distribution, Sokal, Hasford, ELTS and ECOG scores between the two groups. The median time from the diagnosis to initiate imatinib treatment was 23.5 (1- 156) days for Glivec group and 13 (1- 51) days for the generic group (p< 0.05). But the late onset of the treatment was not associated with treatment failure or death within the Glivec group. The median follow-up was 139 (15- 321.1) months for the Glivec group and 59 (15.9- 171.9) months for generic imatinib groups, respectively (p< 0.05). This difference might be explained by the fact that Glivec has been on the market for about two decades. Similar rates of grade > 1 hematological and non-hematological toxicities were seen in Glivec (n= 17, 9.1 %) and generics group (n= 9, 7.4 %), respectively (p= 0.382). Optimal molecular response rate (OMRR) at 3 months was 77.9 % (n= 113) for Glivec and 43.8 % (n= 53) for generics group (p< 0.001). Similarly, the OMRR at 6 and 12 months was significantly higher in original imatinib group. Median EFS was found significantly higher for Glivec group compared to the generic group (97.5 months (95% CI: 159-177) vs 46.3 months (95% CI: 56-93); p<0.001) Conclusion: We found that OMRR of Glivec group in early phase of treatment was significantly higher than the generic imatinib group. The generics group presented with a lower OMRR at 3, 6 and 12th months as well as e lower median EFS. No significant difference in safety concerns was observed between the groups. Generic imatinib formulations may yield lower EFS and OMRR when used in first line for CP-CMLç