Evidence and Efficacy
Dasatinib has significant clinical activity in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) who are resistant to imatinib. Ravandi et al. examined the efficacy and safety of combining Hyper CVAD chemotherapy with dasatinib for 35 newly diagnosed patients, median age 53 (21-79). Dasatinib 50 mg twice a day or 100 mg once a day was given orally for the first 14 days of each 8 cycles of alternating Hyper CVAD, and high-dose cytarabine and methotrexate. Patients who achieved complete remission (CR) were given maintenance of daily dasatinib and monthly vincristine and prednisone for 2 years, followed by dasatinib indefinitely. 94% of patients achieved CR and a median disease-free survival and median overall survival had not been reached at a median follow-up of 14 months, with an estimated 2-year survival of 64%.r
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 Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (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 CR 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 disease free and overall survival 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

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Furthermore, a multicentre trial found the addition of dasatinib in combination with chemotherapy followed by an allogeneic haematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) was feasible. Hyper CVAD + dasatinib treatment was administered and of the 83 (88%) patients who achieved first complete remission (CR1), 41 patients received an allogeneic HCT where a donor was available, followed by daily dasatinib 100mg 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 1.2018
|
Yes |
Yes |
- |
BCCA |
N/A |
N/A |
N/A |
CCO |
N/A |
N/A |
N/A |
|
Toxicity
Dasatinib was discontinued in 12 patients due to pleural effusions (n=6), pulmonary artery hypertension (n=2), gastrointestinal bleeding (n=2), skin cancer (n=1) and subdural bleeding(n=1)r
Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/ pericardial effusions, and elevated transaminases.

© Cancer 2015