Can Subcutaneous Blinatumomab Offer New Option in Rare Acute Leukemia?

Further research may affirm subcutaneous blinatumomab (Blincyto) as a new “paradigm” in the treatment of patients with mixed phenotype acute leukemia (MPAL), according to Ashkan Emadi, MD, PhD.

In a conversation with CancerNetwork^®, Emadi discussed early findings from an investigator-initiated phase 2 trial (NCT07222579) evaluating subcutaneous blinatumomab among patients with CD19-positive MPAL, a rare acute leukemia.¹ Given the rarity of the disease and lack of FDA-approved therapeutic options for this patient population, Emadi and colleagues sought to investigate blinatumomab’s potential efficacy and safety.

Emadi detailed the treatment trajectory of the first patient to receive subcutaneous blinatumomab for MPAL, which reflected an “unprecedented” result for the disease subtype. Additionally, he highlighted how blinatumomab’s subcutaneous formulation may offer quality of life benefits compared with traditional therapeutic strategies in the field.

Emadi is chair of the Department of Medical Oncology, Alexander Bland Osborn Endowed Chair and Distinguished Professor of Medical Oncology, physician in chief of medical oncology, and associate director for clinical research at WVU Cancer Institute.

CancerNetwork: What was the rationale for assessing subcutaneous blinatumomab in patients with MPAL?

The currently approved version of blinatumomab has been an extremely successful story in terms of the improvement of overall survival and quality of life for both adults and children with B-cell acute lymphoblastic leukemia (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 multi-agent chemotherapy for patients with B-cell ALL.^2-4 Subcutaneous blinatumomab has been used in clinical trials by different institutions for the treatment of patients with relapsed or refractory B-cell ALL, but it has never been used for the treatment of MPAL. This patient whom we are reporting [on] is the first patient on the planet Earth—on the globe—with MPAL who has been treated with subcutaneous blinatumomab.

MPAL is a very rare type of acute leukemia, [representing] 1% to 3% of acute leukemia. These cells have both myeloid markers as well as lymphoid markers. The lymphoid marker can be either B cells or T cells. The target population is patients with B/myeloid MPAL. They are about 1% to 2% of all acute leukemias, which is about 500 patients in [the] US per year. It looks like it’s very rare, but if there are 500 patients in the US, that means that there are 10,000 patients everywhere in the world who are diagnosed with this disease. Unfortunately, as of today, there are absolutely no FDA-approved disease-specific therapies for patients with MPAL. [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. It's a clear definition of unmet need.

The idea [behind the trial] was simple. Blinatumomab is very successful for CD19-positive B-cell [ALL], and now we have a much less cumbersome [subcutaneous] formulation of blinatumomab. Why not provide it for patients with CD19-positive MPAL who have absolutely no other options?

How did the first patient who received blinatumomab in this trial respond to therapy?

The first patient is a 77-year-old individual who came in mid-January 2026 with a diagnosis of Philadelphia chromosome–positive B/myeloid MPAL [B-MPAL]. Philadelphia chromosome is a chromosomal abnormality that we see [in approximately] 95% of patients with chronic myeloid leukemia and about 25% of adults with B-cell acute lymphoblastic leukemia. Some patients with B-MPAL also have the Philadelphia chromosome.

Because of her age, [the patient was] not a candidate for cytotoxic, conventional chemotherapy. At the time of diagnosis, she was severely pancytopenic, anemic, thrombocytopenic, and neutropenic. She had about 11% to 15% blasts in her peripheral blood. Her bone marrow, at the time of diagnosis, showed that she had more than 80% blasts, explaining why she was so pancytopenic. The cytogenetic analysis showed that 87% of her bone marrow had Philadelphia chromosome positivity by FISH [fluorescent in situ hybridization analysis].

I started her after a few days of dexamethasone, which is in the protocol approved by the FDA. I gave her a few days of dexamethasone as a pre-phase or cytoreductive [therapy]. Then, she started, on January 16, with the first dose of subcutaneous blinatumomab at 250 µg per day for 7 days. She also started on a tyrosine kinase inhibitor, dasatinib [Sprycel] at 100 mg daily; protocol allows for people to receive that. She tolerated those 7 days perfectly fine. She had no adverse events. She received her dose per protocol, escalating to 500 µg on the 23rd of January, and she tolerated it well. She was discharged from the hospital on that Saturday. In the subsequent weeks, she came in on Monday, Wednesday, and Friday until she finished the 3 weeks outpatient. She received the 500 µg [of blinatumomab] subcutaneously with the dasatinib. She tolerated the chemotherapy very well. Toward the end of the second week, she had to be admitted briefly for cytokine release syndrome [CRS], which showed that the blinatumomab was working.

She never went above grade 1 [CRS]. She was treated with [acetaminophen] Tylenol and 2 or 3 days of intravenous antibiotics as an inpatient. [Afterwards,] she didn't have any more fever. She was discharged again to outpatient and came in to receive her subsequent treatment. On day 26 of the first treatment cycle, I performed the bone marrow biopsy on her. At the time of doing the bone marrow biopsy, her white blood cell count was more than 5000 u/ml; she had way above the 1000 u/ml count. She was red blood cell transfusion independent, and her platelet count was 150,000, so all of her blood cells completely normalized.

By February 13, I was notified that her bone marrow biopsy had no increase in blasts, both aspiration and biopsy, by flow cytometry. On February 16, I was told that her FISH cytogenetic results did not show any Philadelphia chromosome, which is a huge, unprecedented result.

What are the next steps for research in this phase 2 trial? What kinds of outcomes or end points will be assessed in the future?

The trial has 3 cohorts. The first cohort is for newly diagnosed patients with MPAL who are either over the age of [75] or have comorbidities that preclude them from receiving conventional cytotoxic therapy. That cohort will have 2:1 randomization. The total cohort is 45 patients; 30 patients will receive blinatumomab, and 15 patients will receive an alternative, available therapy that is in the protocol and in agreement with the FDA. Cohort B is a smaller cohort of about 10 patients, and these are the patients with MPAL who have achieved complete remission but have minimal residual disease–positive [status] of more than 0.1%. Finally, the third cohort is not randomized; that's a single arm. The third cohort is people with relapsed/refractory MPAL who have received some other chemotherapy from other investigators. That cohort has a sample size of 20.

There is a total of 75 patients for this study. Given the rarity of the disease, we are planning to open this in 15 other sites. There are 3 sites that have already agreed to be our subsites, and we are going to open them in different geographical areas in the US. We are hoping, with the rarity and the opening of 5 sites, hopefully, in 3.5 to 4.5 years, we complete the clinical trial. We are hoping that, if the results continue to be as successful and great as this, this can be a new paradigm and a new standard of care for patients with CD19-positive MPAL.

How feasible is it to administer treatment with blinatumomab in the outpatient setting? How might this benefit patient quality of life?

Subcutaneous blinatumomab is like any other subcutaneous drug that we are giving, like subcutaneous rituximab [Rituxan]. It's only a few minutes after the people arrive in the infusion center that they can get that drug injected under their skin and go home. Right now, because the trial is open here, people must come here or go to the trial center [for treatment]. But if this [becomes] FDA approved, any oncologist in any place near a patient's home can administer this.

It's not limited to a tertiary center. Imagine over 4 weeks, 3 times a week, you go to your infusion center for half an hour or less. By the time you check in, it goes under your skin, and then you leave. [Alternatively], you have a very complicated pump, [which is] the current practice. For 28 days, you get this pump that drips 28 µg per day. For that pump, you need a central line or a port. Imagine you want to take a shower.... Imagine you want to get on an airplane; this pump is going to beep [and get noticed by the] TSA. We do this because it's a great drug, and it has revolutionized treatment of ALL. But having a pump 28 days in a row is not easy. Now, compare that with 3 times a week for 4 weeks, where you go get something under your skin, then say “Bye”; you can go play golf.

References

1. WVU Cancer Institute first in the world to treat ultra-rare leukemia using novel subcutaneous immunotherapy. News release. WVU Medicine. February 17, 2026. Accessed February 24, 2026. https://tinyurl.com/2s4y3xmr
2. FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome-positive B cell. News release. FDA. July 11, 2017. Accessed February 24, 2026. https://tinyurl.com/23vs3bts
3. FDA grants full approval for Blincyto® (blinatumomab) to treat minimal residual disease-positive B-cell precursor acute lymphoblastic leukemia. News release. Amgen. June 21, 2023. Accessed February 24, 2026. https://tinyurl.com/yunbfmzm
4. FDA approves blinatumomab as consolidation for CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. News release. June 14, 2024. Accessed February 24, 2026. https://tinyurl.com/2p5bj9km