A Novel Immunotherapy Gives a Young Mother a Second Chance

 

Lucia Montalvo, 38, was diagnosed with myelodysplastic syndrome in her early 30s. As it can, it soon transformed in 2014 to acute myeloid leukemia, or AML, an aggressive blood cancer that requires similarly aggressive treatment. 

For Lucia, the diagnosis was particularly hard because of her two daughters, one of which was only 7 years old at the time. She recalls thinking, “If I die, what will my daughters do without their mom?”

Unfortunately, Lucia’s case was atypical. Not only did she have a very unusual disease given her young age, but she also had no health insurance and didn’t speak English.

Challenges to Overcome
John DiPersio, MD, PhD
Washington University’s Chief of Oncology and Deputy Director at Siteman Cancer Center

Without insurance, it was difficult to receive the care she needed for her dire diagnosis. Most providers turned her down until she ended up in the service of the Siteman Cancer Center and Washington University team, under the care of John DiPersio, MD, PhD, a medical oncologist, deputy director of Siteman and chief of the Division of Oncology at Washington University School of Medicine.

Her care team confronted tremendous challenges along the way regarding her lack of insurance, but they persisted.

Their first challenge was simply controlling her disease because they were unable to treat her very easily. Fortunately, they were eventually able to get her the aggressive chemotherapy she needed in the hospital, but she relapsed several times. At that point, the team knew her only chance for long-term survival was a stem cell transplant, but she could not have progressive, active leukemia prior or it would certainly fail. 

Hope From a Clinical Trial

Lucia’s options were now even more limited, and she was put on a clinical trial using an immunotherapy called CD123, a dual-affinity re-targeting agent. 

This immunotherapy drug activates the patient’s own immune system to kill the leukemia. Dual means it targets both an antigen on leukemia cells and an antigen on T cells, or immune cells, while affinity means it binds tightly to both of those antigens. By re-targeting, it allows a normal T cell in the body to be redirected to attack the leukemia cells.

The trial, overseen by Dr. DiPersio and lead investigator Geoffrey Uy, MD, is a dose escalation trial open to any patient with relapsed AML. It involves administering a rapidly increasing dose of the drug intravenously over the first week. Unfortunately, it can cause a condition called cytokine release syndrome, which results in side effects such as fever, nausea and capillary leak syndrome

While Lucia did develop these side effects, her team was able to manage them and increase her dosage. Once the maximum dose has been achieved, the drug has shown to induce remission in 20-25% of all patients and 30-35% of patients with primary refractory disease, meaning they had relapsed and were unable to get back into remission — like Lucia.

For Lucia, it was successful in controlling her disease and bringing her one step closer to transplant.

Supported By the SPORE in Leukemia

At the time, this clinical trial was incredibly novel. It was developed in collaboration with the biopharmaceutical company, after the Washington University team expressed interest in testing the drug in laboratory models. They completed all of the preclinical work and wrote the trial, which has since been modified with participation from more cancer centers and has resulted in three publications.

While other diseases have been targeted in a way similar to this, AML has always presented an issue. This is due to the fact that the antigens expressed on AML are also expressed on many normal cells. AML cells are also more inherently immune suppressive, blocking the effects of immunotherapy on their own. Lastly, it releases more of the proteins that cause cytokine release syndrome, resulting in more toxicity. 

“It’s a very difficult problem. No one’s really been able to get a home run,” says Dr. DiPersio. “The response rates are generally low, and the toxicity is generally high. The issue is how to figure it out and make a big difference in AML. This is a start, but we have a long way to go.”

In fact, the clinical trial Lucia took part in has already evolved at Washington University, where they are now studying how to better manage cytokine release syndrome with the use of a JAK inhibitor to reduce the production of cytokines. Another trial using the drug is also opening soon that focuses on patients who have relapsed after transplant. The science behind all of these studies was generated by discoveries made in the lab through the SPORE in Leukemia.

“This was really an institutional effort. Both the first preclinical study and the trial itself were supported by the SPORE in Leukemia,” says Dr. DiPersio. “When we started this, there was really nothing going on for immunotherapy, and since then, many studies have emerged from it.”

More Time With Family

With her leukemia controlled, Lucia’s team was able to move to transplant, after successfully getting her on Medicaid. However, one last complication arose in that Lucia did not have a match donor. Their option was to use a half-match donor, which at the time, was far from a routine approach. On March 5, 2015, Lucia received a haploidentical, or half-matched, transplant from her brother.

Although she experienced some initial side effects of graft-versus-host disease, the transplant was a success. Lucia has no evidence of recurrence, and her bone marrow counts have completely recovered to normal. She is healthy and doing well, which she attributes to the care she received at Siteman. “At the beginning, I was scared,” says Lucia. “I knew it would be hard and that it could fail, but thank God, I am still alive.” 

Now, Lucia is no longer working so she can enjoy more time with her family. Together, they go on bike rides and play games. She is grateful for the time she has with her daughters and husband.

Seeing the impact of work in the lab and in the clinic for patients like Lucia is incredibly rewarding for the Siteman and Washington University team. “Obviously it’s the best part of my job, bar none. Think about what could have happened if we didn’t help Lucia — she wouldn’t be with us today,” says Dr. DiPersio. “There is a lot of joy in doing research and understanding new things, but when you can finally see it help patients, there probably isn’t anything better than that.”

Learn more about ongoing research supported by the SPORE in Leukemia.

You can also read other patient stories here.