Twin-Agent Therapy Evaluated for Philadelphia Chromosome-Positive ALL, CML in Lymphoid Blast Phase

A real-world study has evaluated blinatumomab plus ponatinib combination therapy for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia in lymphoid blast phase (CMLBP). The study was conducted by researchers from the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, who presented their findings at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

The researchers found this dual-agent combination to have efficacy in the study population, namely if used in earlier lines of therapy, and also to be an option for patients with advanced comorbidities if closely monitored.

“TKD [tyrosine kinase domain] mutations, which were enriched in those receiving other TKIs [tyrosine kinase inhibitors] prior to ponatinib, were associated with relapse and reduced survival,” the researchers noted.

The cohort for this single-institution retrospective study included 62 adults who had newly diagnosed, relapsed, or refractory Ph+ ALL or CMLBP, for which they were treated with the combination of blinatumomab plus ponatinib.

Thirty-one patients in the cohort received the combination as frontline therapy, with a median of five blinatumomab cycles and 65% having received at least four. They had a median age of 51 years, and cardiovascular disease (CVD) was present in 52%. In 31 patients, with receipt of additional intrathecal chemotherapy, disease cleared without later central nervous system (CNS) or systemic relapse. The median time to progression (TTP) after therapy initiation was not reached, and with a 25-month median follow-up, was estimated to be 89%. Median overall survival (OS) was not reached, and with a 25-month median follow-up, was estimated to be 86%. There were four patient deaths: one from allogeneic transplant, two from infection after later therapy, and one from management nonadherence.

Twelve patients received the combination as second-line therapy, with a median of two blinatumomab cycles and two patients having received at least four. They had a median age of 48 years. Ten patients responded to the combination and two patients did not, both of whom had TKD mutations. Median TTP was not reached, and with a 25-month follow-up, was estimated to be 71%. Median OS was not reached, and with a 35-month follow-up, was estimated to be 62%. There were four patient deaths: two from disease, one from allogeneic transplant, and one from acute myeloid leukemia.

Nineteen patients received the combination as third-line or later therapy, with a median of two blinatumomab cycles and 21% having received at least four. They had a median age of 58 years; 58% had CVD, and 42% had CNS-positive disease. All patients were previously treated with non–ponatinib TKIs and 15 had TKD mutations. Eleven patients responded to treatment. Among the eight patients with no treatment response, four had compound mutations and one had CMLBP. Over a 28-month median follow-up, the median TTP was found to be eight months, and over a 30-month median follow-up, the median OS was 28 months. There were 11 patient deaths, with nine due to disease, one from infection after later therapy, and one from allogeneic transplant.

The researchers noted that in patients who had a response to the combination, allogeneic transplant consolidation did not improve OS relative to maintenance ponatinib, but “among those with sustained molecular remission of at least 2 years, discontinuation of TKI may be feasible.”

Additional analyses are underway to assess outcomes by molecular response kinetics using next-generation sequencing and quantitative polymerase chain reaction for BCR-ABL.

The researchers included an off-label disclosure of blinatumomab plus ponatinib use for frontline care of Ph+ ALL and for relapsed or refractory CML in blast phase.

Reference

Tobon K, Consalvo K, Kareem SS, et al. Efficacy of combination blinatumomab and ponatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia in lymphoid blast phase (CMLBP) in a real world setting. Abstract #2820. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.