IS GENERIC MESILATE OF IMATINIB LESS INFERIOR THAN GLIVEC?ANALISYS IN BRAZILIAN COHORT
Author(s): ,
Paola Cappelletti
Affiliations:
Laboratory of Molecular Biology, Bone Marrow Transplant Center (CEMO),National Cancer Institute (INCA),RIO DE JANEIRO,Brazil
,
Simone Bonecker
Affiliations:
Laboratory of Molecular Biology, Bone Marrow Transplant Center (CEMO),National Cancer Institute (INCA),RIO DE JANEIRO,Brazil
,
Roberta Bittencourt
Affiliations:
Laboratory of Molecular Biology, Bone Marrow Transplant Center (CEMO),National Cancer Institute (INCA),RIO DE JANEIRO,Brazil
,
Jane Dobbin
Affiliations:
Hematology Service,INCA,RIO DE JANEIRO,Brazil
,
Arthur Moellman
Affiliations:
Hematology Service,INCA,RIO DE JANEIRO,Brazil
Ilana Zalcberg
Affiliations:
Laboratory of Molecular Biology, Bone Marrow Transplant Center (CEMO),National Cancer Institute (INCA),RIO DE JANEIRO,Brazil
EHA Library. Cappelletti P. Jun 12, 2015; 103005; PB1766 Disclosure(s): INCA
CEMO
Paola Cappelletti
Paola Cappelletti
Contributions
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Abstract
Abstract: PB1766

Type: Publication Only

Background
The improvement of the treatment for LMC patients after the introduction of tyrosine kinase inhibitor (TKI) Imatinib (Glivec®, Novartis) speaks for itself. After the developed of Glivec, others TKIs became available on the market. These new drugs, however, come to market with prices to astronomical levels. The introduction of therapies with generic drugs is extremely relevant. In Brazil, mesilate of imatinib (IM) become available in a generic formulation (gIM) by January 2014 with a productive development partnership signed Farmanguinhos/FIOCRUZ, Vital Brazil Institute and Cristália Pharmaceutical Chemicals.

Aims
The objective of this study was analyzed our Brazilian CML patients cohort and evaluate the molecular response of these patients before and after the exchange of the drug (Glivec vs. gIM) and monitoring a small group of CML patients considering only gIM as first line therapy. 

Methods
We analyzed and compared two different groups. The first one has 171 patients who start with Glivec as first line therapy and followed them between 2001 and 2014. All these patients switched to gIM in 2014. The second group has 11 patients who started the treatment with gIM in 2014. For those, the follow-up was 12 months. 

Results
The median time follow-up for patients whom start Glivec was 5.4 years (1.1 – 13.8), while on the other group was 0.4 (0.3 – 1) years. We observed a slight predominance of female on the Glivec first line therapy cohort. Most of the patients (96.8%) were diagnosed in chronic phase in both group; 96.8% and 92.3% respectively. Considering the group who start with Glivec as front line therapy before switch to generic, 9.9% (17/171) of the patients lose MR during the treatment. One of them presented a L452I mutation. In spite of that, they still switch   to gIM. Among 17 patients, 5 (29.4%) gain MR after switch to generic IM.  At this time, these 17 patients are excluded from subsequent analyzes. After switch to gIM, 5.8% of the patients (9/154) lost MMR response or more. Three of them acquire a mutation, 1 patient at 7 months and the other 2 patients, 3 months after change the treatment: L273M, L387M and F359V. L387M mutation was already described as sensitive to IM. F359V-mutated cell lines demonstrated decreased sensitivity to imatinib compared with CML cell lines wild type. One patient present E453A mutation before change the drug. The median time to lose response was 7 months. Only 3.3% (5/154) of the patients gain MR after change to generic IM. We had 11 patients in our cohort who star the treatment with generic IM. Taking account the 3 months cutoff, 72.7% (8/11) of the patients presented levels ≤10% BCR-ABL1 transcripts and 5 of these 8 patients (62.5%; 5/8) achieved MMR at 12 months. None of them discontinuous the treatment.

Summary
In our patient cohort of 'good responders', taking into account that all of the patients who had to switch to second generation TKIs were excluded from this study, the generics were at least non inferior to the original drug in terms of maintenance of response state, efficacy and tolerability when used in the upfront setting, as well as when used subsequently. Prospective studies are needed to address the effectiveness of generic IM in CML patients.

Session topic: Publication Only

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