P203 | IMPACT OF ABCB1 AND ABCG2 POLYMORPHISMS ON BCR∷ABL1 EXPRESSION ONE MONTH AFTER TKI SUSPENSION IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Background. Multidrug resistance proteins ABCB1 and ABCG2 are membrane transporters that can confer resistance to anticancer drugs, including Tyrosine Kinase Inhibitors (TKIs). Various ABCB1 and ABCG2 single nucleotide polymorphisms (SNPs) were studied for their potential role to affect the transporter activity and their impact on clinical response in CML, but little is known about treatment free remission (TFR) achievement. Aim. To investigate the role of the most common ABCB1 and ABCG2 genetic polymorphisms in CML patients after TKI suspension in sustained Deep Molecular Response (DMR). Methods. We analyzed four ABCB1 polymorphisms (C3435T, G2677T, C1236T and T129C) and two ABCG2 polymorphisms (G34A and C421A) in 82 CP-CML patients (median age 67 years, range 28-94) who discontinued TKI therapy. We compared the rates of BCR∷ABL1 transcript detectability one month after TKI suspension across the different genotypes. Statistical analysis was performed using the Cochran-Armitage trend test in an additive model with the number of minor alleles (0, 1, or 2) as the predictor. Results. We found an association between a quantifiable (quant) BCR∷ABL1 transcript vs undetectable (und) one month after TFR and the ABCB1 SNPs C3435T (quant: CC=32%, CT=59%, TT=9% vs und: CC=23%, CT=46%, TT=31%, p=0.0413), G2677T (quant: GG=55%, GT=33%, TT=12% vs und: GG=27%, GT=46%, TT=27%, p=0.0132), and C1236T (quant: CC=50%, CT=41%, TT=9% vs und: CC=25%, CT=46%, TT=29%, p=0.0053), as well as the ABCG2 SNP G34A (quant: GG=82%, GA=14%, AA=4% vs und: GG=100%, GA=0%, AA=0%, p=0.0104). This SNP showed an even stronger association when quant BCR∷ABL1 is further divided between patients maintaining DMR and those in Major Molecular response (MMR) (MMR: GG=86%, GA=0%, AA=14% vs DMR: GG=80%, GA=20%, AA=0% vs und: GG=100%, GA=0%, AA=0% - p=0.0019). For the C1236T SNP, the association was also confirmed using the cut-off of 0.0051% BCR::ABL1, that we had previously defined as predictive of TFR maintenance (quant: CC=58%, CT=42%, TT=0% vs und: CC=27%, CT=47%, TT=26% - p=0.0134). Conclusions. Despite the relatively small sample size, our data suggest that ABCB1 and ABCG2 genotypes affect their function as drug transporters, and this may in some way influence the possibility of maintaining TFR after TKI stop.