ORLANDO (EGMN) – Adding imatinib to standard therapy for Philadelphia chromosome–positive acute lymphoblastic leukemia significantly improves overall, event-free, and relapse-free survival, investigators reported at the annual meeting of the American Society of Hematology.

A comparison of outcomes in the pre- and post-imatinib (Gleevec) eras for patients treated under the same standard therapy protocol (induction therapy followed by allogeneic hematopoietic stem cell transplant [alloHSCT]) showed that 3-year overall survival improved from 25% before imatinib was introduced to 43% after its introduction (P = .0001).

Similarly, 3-year event-free survival rates nearly doubled, from 19% to 37% (P less than .0001), and relapse-free survival went from 36% to 53% (P = .0001), said Dr. Adele Fielding of University College London.

The addition of imatinib increased the complete remission rate by 10% with no increase in transplant-related mortality, and allowed for a near doubling in the rate of alloHSCT.

“Although there are a number of studies which have now been published detailing the value of imatinib in this disease, this is the largest such study, and because of the very large number of patients treated on the same study without imatinib, it allows us to make certain and very sensible conclusions,” Dr. Fielding said.

The trial, designated UKALL12/ECOG2993, initially enrolled 266 patients from 1993 to 2003. These patients (the pre-imatinib cohort) received two phases of induction therapy over 2 months, followed by matched sibling or unrelated donor myeloablative allogeneic hematopoietic stem cell transplant, unless the patient was medically unfit or had no suitable donor.

In March 2003, an additional 86 patients had consolidation with imatinib 600 mg daily after the second induction chemotherapy (late-imatinib cohort). Beginning in late 2005, an additional 89 patients received imatinib concurrently with the second phase of induction chemotherapy (early-imatinib cohort).

All patients who received imatinib resumed the drug, if they were able to tolerate it, for an additional 2 years following the alloHSCT.

Patients who did not undergo transplantation could be put on 2 years of imatinib maintenance at the discretion of the treating institution.

In the pre-imatinib cohort, 82% of patients had a complete response following induction. The addition of imatinib significantly improved responses, with 92% of patients in each of the imatinib cohorts having a complete response (P = .004).

The 3-year follow-up data from the trial show that in addition to the gains in overall, event-free, and relapse-free survival mentioned earlier, patients who received imatinib and who also underwent a per-protocol bone marrow transplant had a 59% 3-year overall survival, compared with 28% for those who received imatinib but not a transplant. Patients who underwent a transplant that differed from the specified protocol had a 49% 3-year overall survival. Rates of event-free survival were similar to those in the overall survival analysis.

Risk of relapse over 3 years among patients who received imatinib and a per-protocol transplant was 25%, compared with 49% for imatinib/non-protocol transplant, and 73% for imatinib but no transplant.

The investigators also found that the early imatinib dosing strategy was associated with better outcomes than the late strategy, with 3-year overall survival rates of 48% vs. 34%, respectively (P = .05), event-free survival of 45% vs. 29% (P = .04), and relapse-free survival of 62% vs. 45% (P = .02).

In a comparison of all patients who achieved a complete response to induction but did not undergo bone marrow transplant, imatinib was associated with an improvement in overall survival (24% vs. 18% for patients treated pre imatinib; P = .02 in multivariate model controlling for age and white blood cell count). But when patients who relapsed or died within the median time to bone marrow transplant were excluded from this analysis, the investigators found no significant difference between the groups, with overall survival of 24% for imatinib and 22% pre imatinib.

“It appears that the improved outcome relates principally to a higher rate of allogeneic transplantation, with a very modest or possibly no long-term benefit to imatinib if transplant is not achieved,” Dr. Fielding concluded in her data presentation.

Dr. Fielding had no disclosures. A coauthor, Dr. Anthony H. Goldstone, disclosed receiving honoraria from Roche.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

奥兰多(EGMN)——来自伦敦大学学院的Adele Fielding 博士在美国血液病协会年会上报告称，在标准治疗基础上加用伊马替尼治疗Ph染色体阳性的急性淋巴细胞白血病(Ph+ALL)，可显著提高患者的总生存率、无病生存率以及无复发生存率。

该结果来自于一项名为UKALL12/ECOG2993的大型研究。该研究最初于1993~2003年选取266名患者组成非伊马替尼治疗组，在行异体造血干细胞移植(alloHSCT)后接受2个阶段的诱导化疗超过2个月。于2003年选取86名患者组成晚期伊马替尼治疗组，在第2阶段诱导化疗后加用600 mg/d伊马替尼。于2005年再选取89名患者组成早期伊马替尼治疗组，在第2阶段诱导化疗同时加用伊马替尼。3组患者诱导化疗的方案和时间是一致的。

结果显示，应用伊马替尼治疗后，患者3年总生存率由25%提高到43%；3年无病生存率由19%提高到37%；无复发生存率由36%提高到53%。且在不增加移植相关病死率的情况下，使完全缓解率提高10%。

但研究者同时指出，如Ph+ ALL患者未接受alloHSCT治疗，加用伊马替尼治疗所获得的长期治疗效果极为有限。

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