ADVERTISEMENT
Dasatinib Added to Induction Therapy Improves Outcomes in Ph+ ALL
Dasatinib added to 2-step induction therapy improves pre-transplant treatment for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), according to results from a Japan Adult Leukemia Study Group (JALSG) study presented at the virtual 2020 EHA Annual Congress.
“The current standard treatment for Ph+ ALL in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission, based on the results of JALSG ALL202 and 208 studies,” explained Isamu Sugiura, MD, Toyohashi Municipal Hospital, Japan, during his presentation.
“Early chemotherapy-related mortality before alloHSCT, relapse mortality, and non-relapse mortality after alloHSCT are still needed to be overcome,” he continued.
The JALSG conducted the multicenter, phase 2 Ph+ALL213 study evaluating the addition of dasatinib to 2-step induction chemotherapy prior to alloHSCT with an aim of minimizing the toxicity of pre-transplant treatments for newly diagnosed Ph+ ALL.
The trial enrolled 81 patients with newly diagnosed Ph+ ALL between Feb 2014 and April 2016, The first step was induction with dasatinib and prednisolone aiming at hematological complete remission (HCR). The second step was intensive consolidation with dasatinib and BFM-like intensive chemotherapy aiming at molecular complete response (MCR).
Consolidation consisted of high-dose methotrexate/cytarabine followed by dasatinib (C1) and a CHOP-like regimen followed by dasatinib (C2). These 2 consolidation regimens were alternated for 4 cycles. Maintenance consisted of 12 cycles of dasatinib with vincristine/prednisolone.
The primary end point of the trial was 3-year event-free survival (EFS). Secondary end points included overall survival (OS), and rates of HCR and MCR.
Of the 81 patients enrolled, 78 were eligible (median age, 45 years). During a median follow-up of 48.1 months, the 3-year EFS and OS were 66.2% and 80.5%, respectively. The 3-year EFS and OS were 66.2% and 84.5% among patients who underwent alloHSCT at CR1 and 79.5% and 90.9% among those who underwent alloHSCT at CMR1.
The HCR rate after induction was 100%. The MCR rates after intensive consolidation and C1 were 56.2% (41 of 73 patients) and 66.2% (47 of 71 patients), respectively. The MCR rates prior to transplant and at day 30 were 75.9% an 92.7%, respectively.
“This study demonstrated [dasatinib]-combined 2-step induction improved pre-transplant treatment, which facilitated alloHSCT and resulted in significantly improved survival,” concluded Dr Sugiura. –Alexis Hyams
Sugiuara I, Noriko D, Hata T, et al. Allogeneic Hematopoietic Stem Cell Transplantation Following Dasatinib-Based Two-Step Induction for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Results of the JALSG PH+ALL213 Study. Presented at: the Virtual 2020 EHA Annual Congress; June 11-21, 2020. Abstract S114.
