Mori, S, Vagge, E, Le Coutre, P, Abruzzese, E, Martino, B, Pungolino, E, Elena, C, Pierri, I, Assouline, S, D'Emilio, A, Gozzini, A, Giraldo, P, Stagno, F, Iurlo, A, Luciani, M, De Riso, G, Redaelli, S, Kim, D, Pirola, A, Mezzatesta, C, Petroccione, A, Lodolo D'Oria, A, Crivori, P, Piazza, R, GAMBACORTI PASSERINI, C
Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR-ABL1 by Q-RT-PCR does not equate to eradication of the disease. Digital-PCR (dPCR), able to detect 1 BCR-ABL1 positive cell out of 10(7) , has been recently developed. The ISAV study is a multicentre trial aimed at validating dPCR to predict relapses after imatinib discontinuation in CML patients with undetectable Q-RT-PCR. CML patients under imatinib therapy since more than 2 years and with undetectable PCR for at least 18 months were eligible. Patients were monitored by standard Q-RT-PCR for 36 months. Patients losing molecular remission (two consecutive positive Q-RT-PCR with at least 1 BCR-ABL1/ABL1 value above 0.1%) resumed imatinib. The study enrolled 112 patients, with a median follow-up of 21.6 months. Fifty-two of the 108 evaluable patients (48.1%), relapsed; 73.1% relapsed in the first 9 months but 14 late relapses were observed between 10 and 22 months. Among the 56 not-relapsed patients, 40 (37.0% of total) regained Q-RT-PCR positivity but never lost MMR. dPCR results showed a significant negative predictive value ratio of 1.115 [95% CI: 1.013-1.227]. An inverse relationship between patients age and risk of relapse was evident: 95% of patients45 years relapsed versus 42% in the class ≥45 to65 years and 33% of patients ≥65 years [P(χ(2) ) 0.0001]. Relapse rates ranged between 100% (45 years, dPCR+) and 36% (45 years, dPCR-). Imatinib can be safely discontinued in the setting of continued PCR negativity; age and dPCR results can predict relapse.
