Use of the anti-CD19 bispecific T-cell engaging antibody blinatumomab given in conjunction with the tyrosine kinase inhibitor (TKI) dasatinib may provide an alternative to allogenic transplant for older adults with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Anjali S. Advani, MD, of Cleveland Clinic, and colleagues in the U.S. Intergroup aimed to evaluate the safety and feasibility of combining blinatumomab with dasatinib and prednisone in older patients with Ph+ ALL. Researchers also sought to estimate disease-free survival (DFS) and overall survival (OS) in this population. Results of the trial were published in Blood Advances.
TKIs used together with steroids have improved the outcomes for older patients with Ph+ ALL who are often poor candidates for intensive chemotherapy or allogenic transplant. While remission rates of patients on TKI-based therapies alone are high, median DFS is short. Blinatumomab has demonstrated significant activity in B-lymphoblastic leukemia (B-ALL) and has been approved by the U.S. Food and Drug Administration in the treatment of relapsed or refractory B-ALL and measurable residual disease (MRD)-positive B-ALL.
The trial by Dr. Advani and colleagues ran from January 2015 to April 2021 and was activated through the National Clinical Trials Network. Researchers enrolled 24 patients with a median age of 73 years (range = 65-87) with Ph+ or Ph-like ALL.
Patients received dasatinib for 56 days (140 mg/day orally) in conjunction with prednisone for 24 days (60 mg/m2/day). Patients who reached complete recovery (CR) or complete remission with incomplete count recovery by day 28 or day 56 and remained in remission through day 84 were given three cycles of post-remission therapy with blinatumomab in conjunction with dasatinib followed by dasatinib and prednisone maintenance. Patients not achieving remission proceeded to reinduction with blinatumomab. Response was assessed at 28, 56, and 84 days.
Results suggest an “excellent tolerability” of blinatumomab in the older population, researchers wrote. Although dose-limiting toxicities (DLTs) were recognized, researchers noted they were no worse than DLTs that typically occur with a regimen of dasatinib and steroids.
Twenty-two patients (92%) achieved a CR during dasatinib and prednisone induction therapy. Compared to similar studies involving younger patients, researchers observed comparable outcomes at three years for DFS and OS (77% and 87%).
What was unique about the trial is that it strictly included patients older than 65 years, allowed comorbidities, and only one patient proceeded to allogenic transplant. Moreover, previous research used ponatinib in conjunction with blinatumomab, but ponatinib may not be a good option for older patients given its risk for cardiovascular events.
“Ponatinib is a better TKI than dasatinib,” Dr. Advani said. “Although it’s excellent, there can be toxicity. Patients can develop mutations with dasatinib treatment … the hope was that the blinatumomab would prevent some of that resistance.”
Researchers anticipate dose adjustments of the TKI therapy for older patients: “The key is seeing what happens with longer follow-up and whether we’re going to sequence this regimen with other therapies,” Dr. Advani said.
Ultimately, researchers hope the outcomes of this study will lead to chemotherapy-free post-remission regimens, potentially with “younger patients who are often offered transplant in the first CR,” Dr. Advani said.
She noted one limitation of the trial, saying, “The follow-up is reasonable but still limited, and longer follow-up will be needed to determine the durability of these results [in the absence of allogenic transplant] ... For young patients, we don’t know the implications of staying on a TKI long term.”
Any conflicts of interest declared by the authors can be found in the original article.
Advani AS, Moseley A, O’Dwyer KM, et al. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia [published online, 2022 Nov 2]. Blood Adv. doi: 10.1182/bloodadvances.2022008216.