TOMASZ SACHA (KRAKOW)
THE USE OF IMATINIB GENERICS IN THE CML THERAPY
The case of female patient who have been treated with branded imatinib, then switched to
imatinib generics and finally who discontinued therapy after achievement of stable and
durable deep molecular response will be presented. The data from Polish Adult Leukemia
Group Imatinib Generics Registry of 347 patients prospectively observed for three years within
the registry who completed 36-month observation (all patients with available RQ-PCR result
at 36th month) will be reported. The cohort consists of previously untreated patients who
started therapy with imatinib generic, and patients switched to generic from branded imatinib
in 2014, who achieved MMR before being switched. All patients have been treated with at
least two generics, and the majority of them received three or more. All patients observed
within the registry have been analyzed for: the frequency of molecular monitoring with RQ-PCR,
the rate of sustained, improved, and worsened molecular response, the rate of CCyR,
MMR, MR4, and MR4,5 loss, and for switching rate between imatinib generics and 2GTKI
during the first and the second year of therapy. The hematologic (3rd or 4th grade), and non-hematologic
adverse events (all grades according to CTCAE criteria) in the first and second
year of therapy have been recorded. Results: Four, three, two, and one RQ-PCR tests were
performed in 53%, 25%, 16%, and 6% of patients during the first year, in 64%, 9%, 12%, and
15% of patients during the second year, and in in 44%, 10%, 21% and 25% of patients during
the third year of observation respectively. The molecular response under therapy with
generics was sustained, improved, and worsened in 70%, 23%, and in 8% of patients at 12
months, in 68%, 21%, and 10% of patients at 24 months, and 86%, 10% and 4% of patients at
36 months therapy respectively. During the first, the second, and the third year of therapy
MMR was lost in 1.5%, 2.3%, and in 0.3%, CCyR in 1.3%, in 0.8% and 1%, MR4.5 in 3.8%, in
6.1%, and 5.2% of patients respectively. One patient lost MMR, CCyR, and CHR in the 24th
month of therapy. During the first, second, and third year of observation 4.5%, 3%, and 0% of
patients were switched to 2GTKI respectively; 3.8%, 1.3%, and 0% for intolerance (non-hematologic
toxicity only), 0.7%, 1%, and 0% for resistance during the first, second and third
year respectively. Hematologic toxicity (grade 3 or 4) during the first and second year was
observed in 2 and 3 patients respectively, non-hematologic toxicity (all grades) occurred in 17
patients during the first year (4.3%), in 36 patients (9,1%) during the second year, and in 14
patients (4%) of treatment. The safety analysis of 91 patients treated with different kind of
imatinib generics will be presented. The effectiveness and safety assessed in a big cohort of
CML patients after three years of observation within Polish Registry suggest that they seem to
be not less effective as Glivec in the therapy of patients with CML CP, however there are some
other reports showing controversial results of the use of different generics, especially those
not approved by medicinal agencies such as FDA or EMA. The quality-controlled generics differ
from copy drugs, substandard drugs and counterfeit drugs. Only 16% of substandard or fake
drugs could be safe. The CML Advocates Network is encouraging all: physicians and patients
to track and record any changes of quality of life on generic product and report any serious
adverse events / lack of efficacy, and to share the experience with the fellow patients’
community.
References:
1. Sacha T, Góra-Tybor J, Szarejko M, Bober G, Grzybowska-Izydorczyk O, Niesiobędzka-Krężel J,
Dudziński M, Wasilewska E, Myśliwiec K, Gil J, Gniot M, Pietkun I, Mędraś E, Hołojda J, Wącław J,