Leukemia: Tomorrow's Treatments Today

Until leukemia can be cured, treatments that have the best results with the fewest side effects are the goal. 

Some cancer cells have genetic mutations (gene changes). The mutations can be matched with immunotherapy drugs — medications that use the body’s own immune system to fight disease. Immunotherapy drugs typically have fewer side effects and greater convenience than chemotherapy. For people with certain blood and marrow cancers, immunotherapy is more promising than ever. 

Researchers with the Froedtert & the Medical College of Wisconsin Cancer Network are part of a national group developing the latest treatment for a rapidly growing form of leukemia called Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Ph+ ALL is known for being one of the most common childhood cancers, but adults can also be affected.

In Ph+ ALL, a genetic mutation overactivates the bone marrow and causes white blood cells to reproduce too quickly. This form of leukemia requires urgent treatment. In the past, the only treatment option was a bone marrow transplant, but it had a survival rate of only 30% to 40%. Clinical trials led to the current standard of care, a combination of chemotherapy and targeted therapy called tyrosine kinase inhibitors (TKIs) that prevents cancer cells from growing. Today, medical researchers are finding that TKIs and immunotherapy may be just as effective. 

“It’s amazing to witness the advancements in treatment for this disease,” said Ehab Atallah, MD, medical oncologist, MCW faculty member and researcher. “Every treatment that is standard of care today is available thanks to people who participated in clinical trials. Because of these individuals, we are at a point of treating Ph+ ALL patients without chemotherapy — and without its short- and long-term side effects, which can be tough.” 

From Diagnosis to Remission: How Three Patients Found Hope Through a Clinical Trial

Mary Schulz, 80, Tiffany Hiler, 45, and Ramon Centeno, 67, are Dr. Atallah’s patients. They shared a diagnosis of Ph+ ALL and chose to participate in a clinical trial through the Cancer Network. Now, each of them is in remission. The results of the phase II clinical trial Mary was a part of paved the way for a phase III trial, which Tiffany and Ramon participated in. 

Mary: A Choice to Pursue an Innovative Treatment

“I wanted the latest and most innovative treatment possible,” Mary said, remembering when she was diagnosed with Ph+ ALL and decided to participate in the clinical trial. “It involved a lot of time in and out of the hospital and a lot of tests, but I loved how meticulously the team tracked my symptoms, lab tests and medications.” 

The standard treatment for Ph+ ALL — TKIs combined with chemotherapy — has a five-year patient survival rate of 70% to 80%. TKIs are a class of drugs that block the enzyme responsible for cell growth and division, preventing cancer cells from multiplying without damaging healthy cells. Chemotherapy destroys cells by damaging their DNA. 

When Mary was diagnosed in 2017, a phase II clinical trial was underway at the Clinical Cancer Center at Froedtert Hospital campus. Researchers were investigating the effectiveness of a chemotherapy-free regimen of TKIs combined with an immunotherapy drug called blinatumomab. 

“Blinatumomab is an antibody drug,” Dr. Atallah said. “It binds with certain white blood cells called T cells, forces the T cells to recognize leukemia and then destroys the leukemia. We did this study because we wanted an alternative to chemotherapy since its toxicity can be intense. The mechanism for blinatumomab, using the body’s own immune system to do the work, is more precise.” 

The study showed patient survival was 70% to 80% with a daily TKI pill and a 28-day continuous infusion of blinatumomab — the same survival rate as patients taking a daily TKI pill and chemotherapy. 

In 2023, trial results were published in Blood, a medical journal of the American Society of Hematology. Dr. Atallah was a local principal investigator for that study. It led to a national phase III clinical trial, in which Dr. Atallah also holds a leadership role, comparing TKIs and chemotherapy to TKIs and blinatumomab. 

“It’s encouraging to see a phase II trial move into phase III,” Dr. Atallah said. “We know chemotherapy has more side effects, but it also has more long-term data. Immunotherapy has shorter-term follow-up and less toxicity. When the trial ends, we’ll be able to look back at data over the years and determine which treatment is best for people with Ph+ ALL.”

Tiffany: Determination and Expert Care

In 2022, Tiffany, a mother of four from Racine and a teacher at the time, went to work on the first day of school. She remembers she could not catch her breath and decided to go to a local emergency department. After a few days in the hospital, she was diagnosed with Ph+ ALL. Tiffany was urgently transferred to Froedtert Hospital, the academic medical center of the Froedtert & MCW health network. Her care team offered the clinical trial as one option for treatment. She and her husband decided participating in the trial was the right choice. Tiffany was randomized to the standard treatment arm, and her leukemia responded to the TKIs and chemotherapy. She is now in remission and takes maintenance medications daily. Tiffany enjoys pursuing her passion for fitness and weightlifting. 

“The diagnosis came as a shock, and going through treatment was hard on me and my family,” Tiffany said. “But I had some of the best people caring for me. It gave me some of the strength I needed. Dr. Atallah helped motivate me to stay positive on the hardest days, and I’m grateful for that. I still go back for labs, and I love seeing the smiling faces of nurses who cared for me.”

Ramon: Finding Hope, Healing and Purpose

Ramon’s experience was similar to Tiffany’s in that he was also urgently admitted to Froedtert Hospital and quickly diagnosed with Ph+ ALL. His care team presented treatment options and went through the details of the clinical trial. 

He decided to participate and was initially randomized to the chemotherapy arm. Later, he was switched to the experimental arm where he was treated with TKIs and blinatumomab. Treatment was a success, and Ramon is in remission. He takes maintenance medication and is back to his hobby of building his own airplane. He said he wanted to be a part of the study because he hopes others will benefit from the trial’s discoveries. 

“My perspective on life is that each day is a gift,” Ramon said. “If I can help others while going through treatment, that’s exactly what I intend to do. Every step of the way, I truly felt cared for and was grateful to be surrounded by such a knowledgeable team. Anytime I had a question, it was answered in depth.”

Extensive Cancer Clinical Trials Program

Mary, Tiffany and Ramon continue to be closely followed by Dr. Atallah and his team, including Guru Subramanian Guru Murthy, MD, MS, medical oncologist and MCW faculty member, along with nurses, clinicians, pharmacists and clinical research coordinators. 

The Cancer Network offers the largest cancer clinical trials treatment program in eastern Wisconsin. Clinical trials are available for people at different points in their disease. People at the beginning stages of disease progression can benefit, as well as people who have exhausted all other options and are at the end of their treatment course. Clinical trials are essential to advancing medicine for future generations and the only way to improve outcomes for people with leukemia and other cancers, including rare diseases.