Abstract
Abstract 668
The cytogenetic response is a confirmed early surrogate marker of the outcome of Ph+ CML patients treated with imatinib (Baccarani et al, JCO 2009;27:6041-51). Many reports and reviews highlight the value of MMolR, defined as a BCR–ABL value equal/less than 0.1% on the International Scale (Hughes et al, Blood 2006;108:20-37). The European LeukemiaNet recommendations use the BCR-ABL level for the definition of optimal response at 12 months (achievement of MMolR) and suboptimal response at 18 months (less than MMolR), but not for the definition of failure (Baccarani et al, JCO 2009; 27:6041-51). As the prognostic value of achieving a MMolR may increase with the introduction of 2nd generation tyrosine kinase inhibitors (TKIs) in the frontline treatment of Ph+ CML, we have reviewed and compared the cytogenetic and molecular data of 4 company–sponsored studies and 4 independent investigator–sponsored studies, for a total number of 2466 patients treated frontline with imatinib (Table 1). The CCgR rates at 12 months ranged between 49% and 88% (median 66%). The MMolR rates at 12 months ranged over a wider range, between 15% and 65% (median 33%). The ratio CCgR/MMolR ranged between 1.31 and 1.90 (median 1.60) in 5 out of 8 studies, while in the other 3 studies (Hammersmith, ENESTnd, and DASISION) the ratio was much higher, ranging between 2.35 and 4.00. Comparing Hammersmith, ENESTnd and DASISION studies to the other 5 studies (IRIS, TOPS, ELN, GIMEMA, and TIDEL), the CCgR rates were similar (median 64% vs. 67%, range 45–73% vs. 58–88%), while the MMolR rates were lower (median 22% vs. 40%, range 15–31% vs. 26–65%). These data cannot be used to argue that a lab, a dose of imatinib, or a study, is “better or worse” than the others, but higlight the consistency of CCgR worldwide and warns from overemphasizing the MMolR rate at 12 months for response evaluation and for treatment adaptation or modification.
| STUDY . | RISK GROUP (Sokal) . | IMATINIBDOSE . | No. of PTS . | CCgR at12 mo. . | MMolR at12 mo . | RATIOCCgR/MMolR . |
|---|---|---|---|---|---|---|
| IRIS(1,2) | All | 400 | 553 | 74% | 39% | 1.90 |
| HAMMERSMITH(3) | All | 400 | 204 | 59% | 15% | 3.93 |
| TOPS(4) | All | 400 | 157 | 66% | 38% | 1.74 |
| ENESTnd(5) | All | 400 | 283 | 65% | 22% | 2.95 |
| DASISION(6) | All | 400 | 260 | 71% | 28% | 2.53 |
| TIDEL(7) | All | 6-800 | 103 | 88% | 47% | 1.87 |
| TOPS(4) | All | 800 | 319 | 70% | 45% | 1.55 |
| TOPS(4) | Low + Int | 400 | 115 | 67% | 43% | 1.56 |
| GIMEMA(8) | Low + Int | 400 | 371 | 85% | 65% | 1.31 |
| ENESTnd(5) | Low + Int | 400 | 205 | 71% | 24% | 2.96 |
| DASISION(6) | Low + Int* | 400 | 210 | 73% | 31% | 2.35 |
| ELN(9) | High | 400 | 108 | 58% | 33% | 1.76 |
| TOPS(4) | High | 400 | 42 | 62% | 26% | 2.38 |
| ENESTnd(5) | High | 400 | 78 | 49% | 17% | 2.88 |
| DASISION(6) | High* | 400 | 50 | 64% | 16% | 4.00 |
| ELN(9) | High | 800 | 108 | 64% | 40% | 1.60 |
| TOPS(4) | High | 800 | 73 | 63% | 40% | 1.57 |
| STUDY . | RISK GROUP (Sokal) . | IMATINIBDOSE . | No. of PTS . | CCgR at12 mo. . | MMolR at12 mo . | RATIOCCgR/MMolR . |
|---|---|---|---|---|---|---|
| IRIS(1,2) | All | 400 | 553 | 74% | 39% | 1.90 |
| HAMMERSMITH(3) | All | 400 | 204 | 59% | 15% | 3.93 |
| TOPS(4) | All | 400 | 157 | 66% | 38% | 1.74 |
| ENESTnd(5) | All | 400 | 283 | 65% | 22% | 2.95 |
| DASISION(6) | All | 400 | 260 | 71% | 28% | 2.53 |
| TIDEL(7) | All | 6-800 | 103 | 88% | 47% | 1.87 |
| TOPS(4) | All | 800 | 319 | 70% | 45% | 1.55 |
| TOPS(4) | Low + Int | 400 | 115 | 67% | 43% | 1.56 |
| GIMEMA(8) | Low + Int | 400 | 371 | 85% | 65% | 1.31 |
| ENESTnd(5) | Low + Int | 400 | 205 | 71% | 24% | 2.96 |
| DASISION(6) | Low + Int* | 400 | 210 | 73% | 31% | 2.35 |
| ELN(9) | High | 400 | 108 | 58% | 33% | 1.76 |
| TOPS(4) | High | 400 | 42 | 62% | 26% | 2.38 |
| ENESTnd(5) | High | 400 | 78 | 49% | 17% | 2.88 |
| DASISION(6) | High* | 400 | 50 | 64% | 16% | 4.00 |
| ELN(9) | High | 800 | 108 | 64% | 40% | 1.60 |
| TOPS(4) | High | 800 | 73 | 63% | 40% | 1.57 |
Euro Score;
O'Brien et al, NEJM 2003;348:994-1004;
Hughes et al, NEJM 2003; 349:1423-32;
De Lavallade et al, JCO 2008; 26:3358-63;
Cortes et al, JCO 2009; 28:424-430;
Saglio et al, NEJM 2010;362:2251-9;
Kantarjian et al, NEJM 2010; 362:2260-70;
Hughes et al, Blood 2008;112:3965-73;
Castagnetti et al, JCO 2010;28:2748-54;
Baccarani et al, Blood 2009; 113:4497-4504.
Molecular studies sere performed: IRIS at 3 labs (Hammersmith, Adelaide; Seattle), Hammersmith at 1 lab, TIDEL at 1 lab (Adelaide), ELN at Bologna and many other labs, TOPS at 3 labs (Naples, Adelaide and Seattle), GIMEMA at 1 lab (Bologna), ENESTnd and DASISION at 1 lab (Portland).
Baccarani:Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding; Wyeth: Consultancy, Research Funding. Rosti:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy. Castagnetti:Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Gugliotta:Novartis: Honoraria.
Author notes
Asterisk with author names denotes non-ASH members.
