Besponsa ‘More Effective’ at Driving Remission for Pediatric B-ALL


Besponsa provides another — and potentially more effective — option outside of traditional chemotherapy for pediatric patients with relapsed or refractory B-ALL.

Image of an adult holding a child's hand.

Besponsa poses as another immunotherapy-based option for children and adolescents with B-ALL who have relapsed.

Besponsa's (inotuzumab ozogamicin) Food and Drug Administration (FDA) approval added to the treatment toolkit for children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL).

Specifically, the FDA approved the drug for children 1 year or older with CD22-positive B-ALL.

“We have another immunotherapy-based option for the treatment of children and adolescents who have B-ALL whose disease has relapsed. So, it just gives us another tool in our kit that's not traditional chemotherapy. It's an immunotherapy-based approach. The more options we have for children with relapsed disease, the better, to cure as many as we can,” said Dr. Jennifer McNeer.

McNeer is a professor of clinical pediatrics at the University of Utah School of Medicine in the Division of Pediatric Hematology/Oncology and the medical director for pediatric hematology/oncology at Primary Children’s Hospital, as well as a member of the leukemia and lymphoma team at the University of Utah and Primary Children’s Hospital.

A single-arm, open-label, multicenter study analyzed the efficacy of Besponsa. In the trial, 22 of the 53 patients (42%), achieved complete response, indicating that their disease completely disappeared. The median duration of complete response was 8.2 months.

The most common side effects that occurred in 20% or more of patients with B-ALL treated with Besponsa were thrombocytopenia (a low platelet count), fever, anemia (a low red blood cell count), vomiting, infection, hemorrhage, neutropenia (a low count of neutrophils, a type of white blood cell), nausea, leukopenia (a low white blood cell count), febrile neutropenia (fever or other signs of infection with a low count of neutrophils), increased transaminases (a type of enzyme), abdominal pain and headache.

The FDA initially approved Besponsa was initially approved in 2017 for the treatment of adults with relapsed or refractory ALL.

McNeer spoke with CURE® about Besponsa's approval and advised families on conversations they should have with care teams.

CURE®: What are the basic principles of how this drug works in B-ALL?

Dr. Jennifer McNeer: Immunotherapy tends to be an antibody-based therapy. It's a targeted therapy, meaning it's more specific to the B cells — in this case, the B lymphoblasts which are the cancerous cells in B-ALL. Besponsa is an antibody against a protein called CD22 that’s on the surface of the lymphoblasts. That antibody is attached to a chemotherapy drug called calicheamicin. So this brings the chemotherapy right up to the B lymphoblast. The cell then takes in the chemotherapy, and the cell is killed through that mechanism. So, it's a targeted therapy. It's more specific to the to the B cells, which is where the B-ALL cancer cells are coming from.

How does this drug compare to the prior standard of care?

These immunotherapies are certainly more effective in getting children back into remission after they've relapsed on our conventional chemotherapy drugs. Then these children will need to go on to some other definitive therapy after that, such as a bone marrow transplant. But we have to be able to get them back into remission first. So, this drug is more effective than conventional chemotherapy in doing that.

Immunotherapies still come with toxicity. With Besponsa, we have to be very careful about liver toxicity ... or impacts on the blood counts. But generally, these immunotherapies overall are less toxic than our conventional chemotherapies.

How can families of pediatric patients help with the management of those side effects?

[Side effects can be handled] through good conversations with the child's oncologist to understand what these side effects may be, [and] what sort of symptoms they may want to monitor for at home. We will be monitoring our clinic with physical exams and lab tests to see if there are any of these toxicities that are developing.

We often will put children on some medications to help limit the liver toxicity with Besponsa. So, there are some other things that we can do to try and help lessen the chances of that, but it [takes] a really good partnership between the treating oncology team and the parents to help these kids through this therapy in the best way possible.

Now that this treatment option is on the table, what unmet needs remain for this patient population?

There are still going to be children whose disease doesn't respond to these approaches after relapse. So, we always are looking for development of new therapies. We're always trying to learn more about the genetics of various patients’ diseases to understand why some children’s leukemia is more resistant to therapy.

Ultimately, what we want to do is try and move these therapies earlier in treatment, if we can do that safely, to decrease the number of children who relapse and have to go through treatment more than once.

We're trying to move these treatments earlier, we're trying to understand in some of these immune therapies that perhaps have better side effect profiles, can they replace some of our conventional and more toxic chemotherapy? I think we are making great progress in childhood ALL. But we certainly still have a ways to go.

What sorts of conversations should caregivers be having with a patient's care team to ensure they are receiving the best care available to them?

In pediatric oncology, many of us work through a collaborative group of some sort. The main one in the United States is the Children's Oncology Group, and many or most pediatric oncologists are members of the Children's Oncology Group, and so are either participating in clinical trials or at least have the latest knowledge in terms of what is our best approach to these. So, I think we're very fortunate in pediatrics because we do work so collaboratively across the country, and even internationally. Parents can ask questions about what are the latest studies that have come out, what is the standard approach to these diseases as we know right now, and whether are there clinical trials available.

I always want to be careful and explain to people [when] we talk to about clinical trials in pediatrics [that] we're very much not talking about experimenting on these children. A lot of them are phase 3 trials where you're taking a very standard approach to therapy and comparing it to a very standard approach to therapy that has a minor modification to it — so, perhaps bringing a new drug into the front line or making some minor modifications to the backbone of chemotherapy to try and improve our outcomes without untoward toxicity.

Transcript has been edited for clarity and conciseness.

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