ORLANDO, FL—An earlier start to imatinib in patients with Philadelphia chromosome positive (Ph+) adult acute lymphoblastic leukemia (ALL) significantly enhances long-term outcomes compared with a later start, according to data from a UK-US cooperative trial reported at the ASH Annual Meeting (Abstract 169).
Final results from the study conducted by the National Cancer Research Institute in the UK and the US Eastern Cooperative Oncology Group showed that any imatinib treatment given during induction for Ph+ ALL significantly enhanced complete response and increased the rate of allogeneic hematopoietic stem cell transplant.
“This translates into a highly significant event-free, overall and relapse-free survival advantage to receiving imatinib during therapy,” said lead author Adele K. Fielding, MBBS, PhD, Senior Lecturer at University College London, UK.
Although comparisons between study cohorts were not randomized, Dr. Fielding said the large differences seen are unlikely to be explained by factors other than treatment.
“There can be no basis for omitting imatinib from the initial therapy of adult patients with Ph+ ALL,” she said. “However, our data show that the best outcome is seen when patients receive imatinib followed by myeloablative allogeneic transplant, where nearly 60% of such patients survive three years from diagnosis.
The three-year follow-up data are from the International Adult ALL trial UKALL12/ECOG2993, sponsored by University College London.
3 Study Groups
Dr. Fielding presented data showing large outcome differences among three study groups:
* “Pre-imatinib” patients who received two phases of induction therapy and allogeneic transplant before imatinib was available.
* “Early imatinib” patients who received imatinib as part of standard induction therapy prior to the transplant.
* “Late imatinib” patients who received imatinib as part of consolidation therapy prior to an allogeneic stem cell transplant.
Dr. Fielding explained that the study opened in 1993 with 266 patients in the pre-imatinib arm, and that following the availability of imatinib, the purpose of the study was modified in 2003 to include and evaluate imatinib as part of consolidation therapy prior to an allogeneic stem cell transplant (late imatinib), or as part of standard induction therapy prior to the transplant (early imatinib).
In the late-imatinib arm, 86 patients received imatinib at 600 mg daily as part of consolidation therapy prior to undergoing an allogeneic stem cell transplant following two induction chemotherapy regimens.
The 89 early-imatinib patients were given imatinib at 600 mg earlier as part of the secondary chemotherapy induction phase prior to allogeneic stem cell transplant.
All patients who received an allogeneic stem cell transplant in the study were given imatinib for two years post-transplant; and if for any reason a transplant was not feasible, the protocol was that imatinib could be given as a maintenance therapy for two years.
Dr. Fielding reported that overall survival reached 25% in the pre-imatinib arm, 34% in the late-imatinib arm, and 48% in the early-imatinib arm.
The event-free survival rate was 19% in the pre-imatinib arm, 29% in the late--imatinib arm, and 35% in the early--imatinib arm. Relapse-free survival rates were 36%, 45%, and 62%, respectively.
She said that prior to the availability of imatinib, only 28% of the pre-imatinib patients went on to receive an allogeneic transplant per the study protocol; the five-year overall survival rate was 40% for those patients who received an allogeneic transplant vs 19% for non transplanted patients.
Among patients in the late-imatinib and early-imatinib arms, 44% were able to undergo allogeneic stem cell transplantation. Three-year overall survival was 59% for those who underwent transplant compared with 28% of those who did not.
During an ASH news conference highlighting presentations of particular interest, Dr. Fielding was asked if imatinib is commonly used to treat Ph+ ALL.
She said that imatinib is not commonly used in the UK, because the data in the literature, all from early Phase I and II studies with short follow-ups, did not justify its use to the regulatory authorities—”They could not justify the expense of the drug,” she said.
The news conference moderator, Peter Emanuel, MD, Director of the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences, noted that although imatinib is standard therapy for Ph+ ALL in some parts of the world, it remains new in many parts of the world.
Also speaking at the news conference about his own study, Jorge Cortes, MD, Chair of the CML Section at the University of Texas MD Anderson Cancer Center, commented that imatinib is routinely used in combination with chemotherapy in ALL, explaining that although this is particularly true in younger patients in the US, imatinib is also commonly used in older ALL patients.