Blood advances 2016-12-27
US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.
Abstract
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 109/L (range, 1 - 410 × 109/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing.
Related Questions
Would concurrent CRLF2/IgH rearrangement affect your treatment recommendations for an adult patient with Ph+ p190 high risk (Age>35, WBC >30) B-cell ALL that was started on induction therapy with ponatinib + blinatumomab?
Short answer: No. Longer answer: We lack a clear understanding of how to change treatment for adults with CRLF2 fusions with Ph- ALL, and this is the situation where it is more clearly understood to have prognostic significance (Roberts et al., PMID 27870571). In my view, it would be very difficult ...
Is there any benefit to transplant patients with Ph+ ALL who have achieved MRD-negativity?
First, some semantics: Asking if there is a "benefit to transplant" may imply there are randomized controlled trials addressing this question, but none to my knowledge have been performed. The last "donor-no donor" trials done in adults with ALL in first remission largely occurred in the pre-TKI era...
How do you decide between blinatumomab or traditional chemotherapy in combination with TKI for upfront treatment of adult patients with Ph + ALL?
This question is likely inspired by the recent publication of a "chemotherapy-free induction and consolidation first-line treatment" for adults with Ph+ ALL (Foà et al., PMID 33085860; GIMEMA LAL2116). The authors reported relatively high rates of MRD- remissions by bone marrow BCR-ABL1 RT-PCR and i...
What maintenance treatment would you recommend for Ph positive ALL following Hyper-CVAD, transplant eligible or ineligible?
While ABL kinase inhibitors (TKIs) are commonly recommended as maintenance post-transplant in Ph+ ALL, the data supporting this practice are relatively soft. Position statements from expert panels convened by EBMT (Giebel et al., PMID 27309127) and ASTCT (DeFilipp et al., PMID 31446198) both general...