Efficacy
A follow-up study confirmed long-term efficacy of the hyper CVAD chemotherapy in combination with dasatinib. 72 patients, median age 55 (21-80) with Ph+ ALL, either untreated or 1 or 2 prior cycles of therapy, were enrolled between 2006 and 2012. This study established dose equivalence between dasatinib 50 mg orally twice daily and dasatinib 100 mg daily and also further amended the protocol to give dasatinib 100 mg daily in the first 14 days of the first cycle, followed by 70 mg daily continuously from the second cycle. Maintenance with dasatinib, vincristine and prednisone was given monthly to patients who achieved CR for 2 years, followed by dasatinib indefinitely. Allogeneic stem cell transplant (SCT) was given in first complete remission (CR1) to eligible patients.r
69 patients (96%) achieved CR, of which 57 (83%) achieved cytogenetic (CG) CR after 1 cycle and 64 (93%) a major molecular response (MMR) at a median of 4 weeks (range, 2 – 38 weeks). At a median of 3 weeks (range, 2–37), minimal residual disease by flow cytometry was negative in 65 (94 %) patients. At a median follow-up of 67 months (range, 33–97), 33 patients (46%) were alive, and 30 (43%) in CR. 12 patients received an allogeneic SCT, and 39 patients died. The median DFS and OS was 31 months (range, 0.3 to 97) and 47 months (range, 0.2 to 97), respectively. Seven relapsed patients had ABL mutations, including 4 with T315I.r
Figure 1: A) Disease-free survival, B) Overall survival and C) Event-free survivalr
© Cancer 2015
Furthermore, a multicentre trial found the addition of dasatinib in combination with chemotherapy followed by an allogeneic haematopoietic cell transplant (HCT) in patients with Ph+ ALL was feasible. Hyper CVAD + dasatinib treatment was administered, and of the 83 (88%) patients who achieved CR1, 41 patients received an allogeneic HCT where a donor was available, followed by daily dasatinib 100 mg starting from day 100. 33 patients actually received dasatinib post-HCT, and 30 (91%) of them required at least one dose reduction. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. At median follow-up of 36 months (range, 9 - 63) for the overall cohort, overall survival (OS) was 69%, event-free survival (EFS) 55%, and relapse-free survival (RFS) 62%. The 12-month RFS was 71% and OS 87% after transplant.r
Source |
Study & Year Published |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
Phase II trials |
Ravandi et al. 2010r |
Yes |
Yes |
- |
Phase II trials |
Ravandi et al. 2015r |
Yes |
Yes |
- |
Phase II trials |
Ravandi et al. 2016r |
Yes |
Yes |
Hyper CVAD + dasatinib followed by allogeneic HCT |
Guidelines |
Date published/revised |
Supports Use |
Is the dose and regimen consistent with the protocol? |
Comments |
NCCN |
Acute lymphoblastic leukaemia
Version 1, 2021
|
Yes |
Yes |
- |
BCCA |
N/A |
N/A |
N/A |
- |
CCO |
N/A |
N/A |
N/A |
- |