The Achievement of An Early Complete Cytogenetic Response (CCyR) Is A Major Determinant for Outcome In Patients (pts) with Early Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs).

Abstract

AbstractAbstract 3429The achievement of a CCyR is a known major surrogate endpoint in the treatment of pts with CML that has shown correlation with survival improvement. Second generation TKIs (2nd TKI) have shown significant activity in pts with CML post imatinib (IM) failure and have recently shown superiority when compared to IM 400 mg standard of care in pts with newly diagnosed CML –CP. We assessed the correlation between the achievement of an early CCyR and event-free survival (EFS as defined by the IRIS trial) and overall survival (OS) in sequential phase II trials run at our institution in pts with newly diagnosed CML in CP treated with IM 400 mg daily (n=73), IM 400 mg BID (n=208), and 2nd TKI (n=154). Patient and disease characteristics at start of treatment were listed in Table 1. The overall rates of CCyR were 87 %, 91%, and 96% for pts receiving IM 400 mg/d, 400 mg BID, and 2nd TKI (p = 0.06). The rates of major molecular response (MMR) were 77%, 87%, and 89%, respectively (p = 0.05). Their 3-year EFS and OS rates were 85%, 92%, and 97% (p=0.01), and 93%, 97%, and 100% (p = 0.18), for pts receiving IM 400 mg daily, IM 400 mg BID, and 2nd TKI, respectively. The rates of 3-, 6-, and 12-month (mo) CCyR of the total group were 65%, 83%, and 89%, respectively. Pts with 3-, 6-, and 12-mo CCyR had statistically a significantly better outcome with 3-year EFS and OS rates of 98%, 97%, and 98% and 99%, 99%, and 99%, respectively compared to 83%, 72%, and 67% and 95%, 90%, and 94%, in pts who did not achieve a CCyR. There was no difference in EFS and OS in pts who achieved a CCyR whether they received IM 400 mg daily, IM 400 mg BID, or 2nd TKI (Table 2.). In conclusion, 2nd TKI induced higher rates of CCyR and MMR than IM. The achievement of an early CCyR remains a major determinant for outcome of pts with early CP-CML regardless of the TKI.Table 1Patients characteristicsParameter400mg800mg2nd TKINo. patient treated73208154Age (years)Median (range)48 (15–78)48 (17–84)47 (18–85)SplenomegalyYes (%)16 (22)59 (28)41 (27)Hemoglobin (g/dl)Median (range)12.7 (7.9–15.7)12.4 (6.2–16.7)12.2 (6.7–15.8)WBC (× 109/L)Median (range)20.5 (1.6–277)27.9 (2.2–283)31.8 (0.8–342.5)Platelets (× 109/L)Median (range)367 (103–1043)353 (58–1476)299 (73–2000)Peripheral blast %Median (range)0 (0–2)0 (0–12)0 (0–7)baso %Median (range)3 (0–16)3 (0–19)3 (0–19)Marrow blast %Median (range)1 (0–6)2 (0–14)2 (0–8)baso %Median (range)2 (0–9)3 (0–15)2 (0–12)Sokal risk, no (%)Low50 (68)132 (63)118 (77)Intermediate22 (30)57 (27)27 (18)High1 (2)19 (9)9 (6)Ph + > 90 %yes (%)67/72 (93)195 (94)133 (86)Clonal evolution (%)Yes (%)2 (3)7 (3)11/151 (7)Table 2OutcomeTotal group3mo-CCyR6mo-CCyR12mo-CCyRynpynPYnP3-yr EFS9883<0.0019772<0.0019867<0.0013-yr OS99950.079990<0.00199940.001IM 400mg3-yr EFS92810.1297740.0019872<0.0013-yr OS100880.046100870.09100880.046IM 800 mg3-yr EFS97840.0059768<0.0019858<0.0013-yr OS98970.9399920.001991000.032nd TKI3-yr EFS10080<0.0019967<0.00199NA (no patient)NA3-yr OS100100NA (no death)100100na100NA (no patient)NAp-value (PFS/OS)0.13/0.240.41/0.920.9/0.6 Disclosures:Jabbour:Novartis: Honoraria; BMS: Honoraria. Kantarjian:Novartis: Research Funding. Cortes:Novartis: Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding.