PB1925 COMPARATIVE STUDY OF GLIVEC VERSUS STATE SPONSORED GENERIC IMATINIB MESYLATE AS FIRST LINE THERAPY IN CHRONIC MYELOID LEUKEMIA‐ CHRONIC PHASE

Abstract

Background:In a developing economy like India, Imatinib usage has increased manifold after generic formulations were introduced. 25 brands of generic Imatinib are approved by the Drug Controller General of India. The efficacy and safety of these brands have been repeatedly questioned by different studies. In most of these studies, generic Imatinib were used as a switch from the innovator. Institute of Hematology and Transfusion Medicine (IHTM) in Medical College, Kolkata is state run institute where two generic brands of Imatinib (Veenat; Natco, and Imatinate; KLabs) are available free of cost to the patients. Also there are patients who were on Glivec from the GiPAP and Max foundation at either free of cost or reduced cost. We took this opportunity to initiate a study to compare the efficacy and safety of these generic brands with the innovator brand (GIG vs IIG).Aims:1. To study the response rates, hematologic and non‐hematologic toxicities, tolerance, compliance and drop out rates of patients on generic Imatinib (GIG)2. To compare the above parameters in patients on innovator Imatinib (IIG)Methods:68 treatment naive CML‐CP patients who were started on generic Imatinib 400 mg/d from July 2015 to April 2016 were enrolled in the study. They were followed up for a median period of 30 months. The results were compared with 70 patients treated in our institute since Jan, 2014 on GiPAP program. Cytogenetic responses were assessed by FISH on bone marrow aspirates on 6 and 12months, and molecular responses were assessed by standardised qT‐ PCR on 3, 6, 12, and 18months of therapy to a resolution of 1 in 10‐4. Patients who were non‐compliant to therapy, response assessment and who failed hematologic response at 3 months were excluded from the analysisResults:Among the 60 patients of GIG included in the analysis, 43 were on Imatinate @KLabs and 17 were on Veenat @Natco. In GIG, 41.6% and 66.6% achieved complete cytogenetic response (CCyR) at 6 and 12 months as compared to 46.2% and 72.1% in IIG (p > 0.05). The rates of optimum molecular responses (ELN 2013) in GIG at 3 and 6 months were 90% and 80% as compared to 92% and 86% in the IIG (p > 0.05). However, the rates of MMR at 12 months in GIG and IIG were 63.3% and 71.4% respectively (p < 0.05). The rates of failure of response by 18 months in GIG and IIG were 33.3% and 17.4% (p < 0.05). In a median follow up of 30 months, 9 patients in GIG progressed to accelerated or blast phase and 20 patients were switched to 2nd line agents. In the IIG, 4 patients progressed and 12 patients were switched to 2nd line TKIs (p < 0.05). There were 3 deaths in GIG and 2 in IIG. Grade 1/2 hematologic toxicities occurred in 100% patients in IIG as compared to 94% in GIG. Grade 3/4 hematologic toxicities occurred in 30% of IIG and 26% in GIG (p > 0.05). Among the non‐hematologic toxicities, skin hypo‐pigmentation, gastritis, muscle cramps and arthritis were most common occurring in 58%, 50%, 30% and 24% in IIG and 50%, 44%, 32% and 30% in GIG. The rates of intolerance and therapy withdrawal are 10% in GIG as compared to 15% in IIG (p > 0.05).Summary/Conclusion:When compared to the innovator brand (Glivec @Novartis), early cytogenetic and molecular responses in patients on generic Imatinib were similar. However, responses at 12 months, rates of failure of Imatinib, and progression of disease are significantly inferior in the GIG and more patients in GIG were switched to 2nd line TKI. Assessment of Deep molecular response rates might yield more significant results. The groups were similar in toxicity profile and therapy discontinuation