First-in-World Trial Tests Subcutaneous Blinatumomab for Rare Mixed-Phenotype Acute Leukemia

West Virginia University Health System Cancer Institute in Morgantown has dosed its first patient in a first-in-world phase 1/2 clinical trial (NCT07222579) evaluating the efficacy of subcutaneous blinatumomab (Blincyto) in patients with CD19-positive mixed-phenotype acute leukemia (MPAL). The first patient enrolled in the trial initiated treatment with blinatumomab on January 16, 2026.

MPAL represents a rare and challenging subset of acute leukemias, accounting for approximately 1% to 3% of all cases. Characterized by the presence of both myeloid and lymphoid markers on malignant cells, MPAL currently lacks FDA-approved, disease-specific therapies. There are only an estimated 500 cases of MPAL in the U.S., 10,000 worldwide. Clinicians typically manage the condition using regimens adapted from acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

For people over the age of 80, the median survival of patients with MPAL is only 2 months; only 3.5% of people with this disease are alive in 2 years. For people over the age of 70, only 5.5% are alive in 2 years. The median survival rate for adults with MPAL was less than 11 months, according to a 2010 study in "Blood", a publication of the American Society of Hematology.

Standard blinatumomab administration requires a 28-day continuous intravenous infusion via a portable pump, which necessitates central venous access and frequent bag changes. The subcutaneous formulation is designed to provide comparable therapeutic exposure while reducing treatment complexity. In the trial protocol, patients receive 250 µg daily for the first 7 days, followed by 500 µg administered 3 times per week.

The trial is designed to enroll up to 75 patients across 3 distinct cohorts: Cohort A includes newly diagnosed patients over age 75 or those with comorbidities that preclude intensive chemotherapy. Cohort B includes patients in morphologic complete remission who remain minimal residual disease (MRD)-positive. Cohort C includes patients with relapsed or refractory disease.

The trial's first participant was a 77-year-old woman with Philadelphia chromosome-positive (Ph+) B-myeloid MPAL. At diagnosis, she presented with 83% bone marrow blasts and severe pancytopenia. Following a dexamethasone pre-phase, she received subcutaneous blinatumomab in combination with the tyrosine kinase inhibitor dasatinib (Sprycel).

By day 26 of cycle 1, the patient had achieved complete hematologic recovery and was transfusion independent. Subsequent bone marrow analysis showed no detectable blasts, and Philadelphia chromosome positivity was no longer evident by fluorescence in situ hybridization (FISH). After a single cycle of therapy, the patient experienced complete remission with full hematologic recovery, which included transfusion independence and the absence of the Philadelphia chromosome. Additionally, treatment transitioned fully to the outpatient setting after the first week.

Safety monitoring remains essential, as the therapy is associated with cytokine release syndrome (CRS). The first patient experienced grade 1 CRS, which was managed with supportive care consisting of Tylenol and "2 or 3 days" of IV antibiotic and was able to resume treatment after the CRS was managed. The regimen "was extremely well tolerated." While the first week of treatment requires inpatient observation, the protocol allows for a transition to full outpatient care for the remainder of the cycle.

For oncology nurses and advanced practice providers, the transition to subcutaneous delivery may significantly streamline care. The formulation eliminates the need for 28-day continuous pumps and central lines, which often interfere with a patient's daily activities. "Only a few minutes after the people arrive in the infusion center, they get [subcutaneous blinatumomab] injected under their skin and they go home."

The currently approved version of blinatumomab has been an extremely successful story in terms of the improvement of overall survival and quality of life of patients for both adults and children with B-cell ALL. Continuous infusion of blinatumomab is approved for relapsed/refractory B-cell ALL for minimal residual disease–positive B-cell ALL and for up-front treatment in combination with multiagent chemotherapy for patients with B-cell ALL. Subcutaneous blinatumomab has been used in clinical trials by different institutions for treatment of patients with relapsed or refractory B-cell ALL, but it has never been used for the treatment of MPAL.

Treatment costs for a similar type of leukemia for people ages 50 to 64 ranged between $200,000 and $550,000, according to a 2017 study that appeared in the journal "Biology of Blood and Marrow Transplant". But many adult cases of MPAL are diagnosed in people over age 65, which limits treatment options. The only cure for this disease is bone marrow transplant, but patients over age 75 or who have comorbidities are not eligible for transplants.

In addition to the WVU Cancer Institute in Morgantown, the study will enroll patients at 15 other sites over four years. As the trial expands to an expected 15 sites across North America, investigators aim to determine if these early results can be replicated in a larger population, potentially establishing a new standard of care for CD19-positive MPAL.