Long-Term Follow-Up of the Imatinib GRAAPH-2003 Study in Newly Diagnosed Patients with De Novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A GRAALL Study

Abstract

We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response).

A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study

“…5,6,10,12,13,15,[18][19][20][21]34,35 Furthermore, our schedule has the advantage that there are fewer deaths during induction treatment, in contrast to the majority of the combination studies in which, with few exceptions, 5 toxic deaths were recorded in 2%-7% of cases. 6,8,[12][13][14][18][19][20] Indeed, toxicity was recorded in the initial combination protocol (imatinib+chemotherapy) that led to the final amendment to a sequential strategy. These results indicate that the induction treatment for adult Ph + ALL can be effectively based on the administration of imatinib plus steroids, without systemic chemotherapy, which enables a CHR to be obtained in virtually all patients with no deaths in induction.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Prior to the introduction of TKI, prognosis was very poor, with virtually no adult patients (<5%) cured with standard chemotherapy; median survival was 8-10 months unless an allogeneic hematopoietic stem cell transplant (allo-SCT), the only potentially curative strategy, could be performed. [22][23][24][25] Today, treatment with TKI, with [5][6][7][8][9][10][12][13][14][15][18][19][20][21] or without 11,16,17 systemic chemotherapy, represents the most appropriate first-line management of patients with Ph + ALL in terms of rates of complete hematologic remission (CHR) and disease-free survival (DFS). Imatinib has been incorporated into different schedules either in induction [5][6][7]10,[12][13][14][18]…”

“…[22][23][24][25] Today, treatment with TKI, with [5][6][7][8][9][10][12][13][14][15][18][19][20][21] or without 11,16,17 systemic chemotherapy, represents the most appropriate first-line management of patients with Ph + ALL in terms of rates of complete hematologic remission (CHR) and disease-free survival (DFS). Imatinib has been incorporated into different schedules either in induction [5][6][7]10,[12][13][14][18][19][20][21] or following induction 8,10 in cohorts including also elderly patients, 8 with CHR rates varying from 72% to 96%. Moreover, the use of imatinib can also act as a "bridge" to an allo-SCT for those patients eligible.…”

“…12,19,[37][38][39][40][41][42][43] Furthermore, they strengthen the notion that MRD negativity should be regarded as a major goal in Ph + ALL treatment. Indeed, with few exceptions, 20,38 it is now well established that BCR-ABL1 transcript levels correlate with response. Lee et al 37 were able to demonstrate that a 3-log reduction in BCR-ABL1 transcripts after one month of imatinib treatment strongly predicted a reduced risk of relapse and confirmed these results in a subsequent study.…”

“…46,47 In contrast, Yanada et al 38 observed no association between rapid achievement of BCR-ABL1 negativity and long-term outcome after an initial imatinib/chemotherapy induction regimen, and the GRAAL group also reported that early MRD evaluation did not significantly influence patient outcome, either in terms of OS or DFS. 20 One issue that remains open to discussion concerning the role of MRD is represented by the substantial differences in the way PCR for BCR-ABL1 detection is performed, how results are reported in different laboratories worldwide, and the timing of MRD evaluation. The indications suggested by White et al 48 will hopefully lead to an international standardization of the assessment of the levels of BCR-ABL1.…”