Zhi-Ping Jiang1, Xie-Lan Zhao1, Naoto Takahashi2, Sabrina Angelini3, Biswajit Dubashi4, Li Sun5, Ping Xu5. 1. Laboratory of Clinical Pharmacology, Department of Hematology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, People's Republic of China. 2. Department of Hematology, Nephrology, & Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita city, Akita 010-8543, Japan. 3. Department of Pharmacology, University of Bologna, Bologna 40126, Italy. 4. Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry 605 006, India. 5. Clinical Pharmacy & Pharmacology Research Institute, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan Province 410011, People's Republic of China.
Abstract
AIM: The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C0), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML). METHODS: A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C0 on clinical outcome in CML patients. Subsequently, a series of meta-analyses were performed, including up to 23 studies with 2577 patients, on the effect of genetic polymorphisms of ABCB1 and ABCG2 on the clinical response to IM. RESULTS: Meta-analysis revealed that patients who achieved a major molecular response (MMR) have a significantly higher IM C0 than those who failed to achieve an MMR. We also found that the patients who achieved a complete cytogenic response (CCyR) have a significantly higher IM C0 than those who did not achieve a CCyR. However, no significant difference in IM C0 was found between the complete molecular response and non-complete molecular response groups. Additional analysis showed that ABCG2 421 variant A allele was significantly associated with a higher rate of MMR and overall response, especially in Asian patients. Meta-analysis did not reveal a correlation between ABCB1 C3435T and C1236T polymorphisms with any clinical response to IM. However, the G2677T/A polymorphism could play a role in IM response in the recessive model. CONCLUSION: This meta-analysis demonstrates that there was a significant correlation between the IM trough concentration and clinical responses, especially MMR and CCyR, in CML patients. Furthermore, we found that the probability of successful treatment was correlated with the ABCG2 C421A polymorphism, at least within the Asian population. We failed to determine an association between ABCB1 polymorphisms and IM response, although the G2677T/A polymorphism might be involved. However, further large-scale investigations using more sensitive genotyping methods would be required to confirm this.
AIM: The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C0), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML). METHODS: A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C0 on clinical outcome in CMLpatients. Subsequently, a series of meta-analyses were performed, including up to 23 studies with 2577 patients, on the effect of genetic polymorphisms of ABCB1 and ABCG2 on the clinical response to IM. RESULTS: Meta-analysis revealed that patients who achieved a major molecular response (MMR) have a significantly higher IM C0 than those who failed to achieve an MMR. We also found that the patients who achieved a complete cytogenic response (CCyR) have a significantly higher IM C0 than those who did not achieve a CCyR. However, no significant difference in IM C0 was found between the complete molecular response and non-complete molecular response groups. Additional analysis showed that ABCG2 421 variant A allele was significantly associated with a higher rate of MMR and overall response, especially in Asian patients. Meta-analysis did not reveal a correlation between ABCB1C3435T and C1236T polymorphisms with any clinical response to IM. However, the G2677T/A polymorphism could play a role in IM response in the recessive model. CONCLUSION: This meta-analysis demonstrates that there was a significant correlation between the IM trough concentration and clinical responses, especially MMR and CCyR, in CMLpatients. Furthermore, we found that the probability of successful treatment was correlated with the ABCG2C421A polymorphism, at least within the Asian population. We failed to determine an association between ABCB1 polymorphisms and IM response, although the G2677T/A polymorphism might be involved. However, further large-scale investigations using more sensitive genotyping methods would be required to confirm this.
Authors: Sara Galimberti; Cristina Bucelli; Elena Arrigoni; Claudia Baratè; Susanna Grassi; Federica Ricci; Francesca Guerrini; Elena Ciabatti; Carmen Fava; Antonio D'Avolio; Giulia Fontanelli; Giovanna Rege Cambrin; Alessandro Isidori; Federica Loscocco; Giovanni Caocci; Marianna Greco; Monica Bocchia; Lara Aprile; Antonella Gozzini; Barbara Scappini; Daniele Cattaneo; Anna Rita Scortechini; Giorgio La Nasa; Alberto Bosi; Pietro Leoni; Romano Danesi; Giuseppe Saglio; Giuseppe Visani; Agostino Cortelezzi; Mario Petrini; Alessandra Iurlo; Antonello Di Paolo Journal: Oncotarget Date: 2017-09-30