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ASH report support generic imatinib formulations in Poland, India


58th American Society of Hematology Annual Meeting & Exposition;
San Diego, California, USA: 3–6 December 2016

: Positive findings on the use of generic imatinib in Poland and India for patients with chronic phase chronic myeloid leukemia (CML) have been reported at the 2016 American Society of Hematology Annual Meeting & Exposition in San Diego, California, USA.

Tomasz Sacha, from Jagiellonian University Hospital in Krakow, presented data from the Polish Adult Leukemia Group (PALG) Imatinib Generics Registry indicating that “tested generics of imatinib seem to be as effective as Glivec,” with no evidence of a higher rate of switching to a second-generation tyrosine kinase inhibitor (2GTKI).

However, he noted that patient analysis was hampered by the use of up to 20 different generic formulations and the frequent switching between different generic imatinib formulations in individual patients.

The PALG registry holds information on 726 patients treated at 27 centers and followed up by 16 certified laboratories for 1 year. This included 99 patients who were treated only with generic formulations and 627 patients who switched from the branded imatinib to generic formulations after achieving a major molecular response (MMR; BCR–ABL1 ≤0.1%). The most common generics given were Nibix (70.9%) and Meaxin (23.3%).

Sacha highlighted 2012 survey data showing that 31% of 1165 CML patients were monitored by polymerase chain reaction less frequently than the recommended four tests per year. This was confirmed in the PALG registry, with just 53% of patients monitored four times over 1 year, 25% three times, 16% twice, and 6% once.

Review of generic imatinib efficacy at 1 year showed that among 92 newly treated patients 65% achieved an early molecular response (MR), defined as a BCR–ABL1 below 10%, within 3 months.

This “corresponds well” with the 65–66% rates reported in the ENESTnd, Dasision, and BELA clinical trials with branded imatinib, Sacha noted.

And 53% achieved BCR–ABL1 reduction to <1% at 6 months, with similar rates for the Nibix, Meaxin, and combined generic groups. These results are comparable to the 57% rate of first complete cytogenetic response achieved by patients in the EUTOS registry given branded imatinib, the presenter said. Overall, MMR was achieved by 53% at 12 months, with again comparable rates for those given Nibix and Meaxin formulations, as well as with that from the EUTOS registry, at 41%.

In all, 26% of patients switched to a 2GTKI, with resistance cited in 13%, progression to accelerated or blast phase in 1%, and intolerance in 12%. Grade 3–4 hematologic and non-hematologic toxicity were reported in 3% and 40%, respectively, with one patient and 12% of patients switching to a 2GTKI, respectively.

Sacha also reported 1-year efficacy results for 627 patients who switched from branded imatinib to generic therapy, showing that MR was sustained in 65% of patients, worsened in 15%, and improved in 19%. Loss of responses reported during generic treatment included complete cytogenetic response in 0.3%, MMR in 1.3%, MR4 in 10.3%, and MR fluctuation in 10.9%.

At 1 year, grade 3–4 hematologic toxicity was reported in 0.5% of 892 patients given generics and 19.3% of 172 had all-grade non-hematologic side effects. Of the 4.5% of patients who switched to a 2GTKI, 3.8% cited intolerance, 0.78% resistance, and 0.56% both intolerance and resistance.

Summarizing his findings, Sacha concluded that “although our observations are short [… ] the data might suggest that generic imatinib is as effective as Glivec, with an acceptable profile of intolerance because we did not find an increased risk of switching to a 2GTKI.”

The second study on generic imatinib use in CML was reported to the meeting by Danthala Madhav, from Nizam’s Institute of Medical Sciences in Hyderabad, India, who said that the innovator and generic versions of imatinib were “comparable for both efficacy and safety.”

He presented follow-up data from CML patients who received frontline branded imatinib (n=1193) or the generic Veenat (n=174) at a single institution between 2008 and 2014, the majority of whom were in the chronic phase.

After 44 months, the patients given branded imatinib and generic imatinib had comparable rates of complete cytogenetic response (67.4 vs 64.3%), MMR (21.7 vs 13.7%), and MR4 (17.1 vs 24.1%).

But Madhav noted that real-time quantitative polymerase chain reaction or cytogenetic testing results were missing for 19.3% and 22.9% of the branded and generic imatinib treatment groups, respectively, despite participation in a sponsorship program.

Adherence rates to TKI therapy were “poor”, at just 16% with the branded imatinib and 17.2% with generic imatinib.

Of note, adherence was adversely affected by patient educational attainment and the “assumption of a cure”, as well as by recent bereavement and the “stigma” of a cancer diagnosis and the need for regular hospital visits, Madhav told the meeting.

Overall, 7.7% of patients given branded imatinib experienced progression to accelerated or blast phase disease versus 7.4% of those given the generic formulation.

Imatinib resistance mutations were screened for in just 11.0% and 17.8% of patients, respectively, and kinase domain mutations were detected in 4.3% versus 8.0%, a significant difference with a p value of 0.034. The most common mutation detected in both treatment groups was T315I.

Following imatinib treatment failure or disease progression, imatinib dose was escalated in 20.8% of the branded and 17.2% of the generic groups, with 2.1% versus 4.5% moving onto nilotinib, 0.9% versus 5.1% to dasatinib, and 0.9% versus 2.2% to hydroxyurea.

Overall, event-free survival was an average of 2025 days for the branded imatinib treatment groups versus 1752 days for the generic formulation group, giving a significant difference at a p value of 0.021.

The corresponding rates of failure-free survival were a comparable 1908 versus 1758 days, he added, whereas transformation-free survival significantly differed at 2252 versus 2020 days (p=0.03).

Nevertheless, overall survival did not significantly differ between the branded and generic treatment groups, at 2324 and 2156 days, respectively.

Finally, safety analysis showed that grade 1–2 non-hematologic adverse events were comparable between the study groups, except for a “slightly higher incidence of myalgia and edema” in the generic arm, Madhav said.

Generic-treated patients also showed a higher rate of grade 3 skin rash than patients given the branded agent, at 2.8% versus 0.2%, but hematologic any-grade and grade 3–4 events were also comparable between the groups.

Concluding that the generic and branded drugs have comparable efficacy and safety, Madhav commented that “as a physician [it] is difficult to choose which to use but at the end it comes down to the price.”

“At US$ 20.56 per month, generic imatinib has price in its favour in comparison to the innovator which now costs six times higher, at US$ 138.00 amount in India.”


By Lynda Williams, Senior medwireNews reporter

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