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Alternative Treatment Options Emerging for Relapsed Pediatric Patients With ALL

Danielle Bucco
Published: Monday, Nov 27, 2017

Susan R. Rheingold, MD
Susan R. Rheingold, MD
The September 2017 FDA approval of tisagenlecleucel (Kymriah), the chimeric antigen receptor (CAR) T-cell therapy, has already made a significant impact on pediatric patients with acute lymphoblastic leukemia (ALL).

, Rheingold, medical director of the Oncology Outpatient Clinic, physician with the Cancer Center at Children’s Hospital of Philadelphia, discusses the impact of CAR T-cell therapy on patients with ALL and options for patients who relapse on treatment.

OncLive: What is the role of CAR T-cell therapy in pediatric ALL?

Rheingold: CAR T-cell therapy is not yet approved for upfront treatment. However, for relapsed disease, it has made a significant change in the number of children it will put back into remission and ultimately cure. It is probably the most promising new cancer therapy in a long time for any type of cancer. However, it is not a frontline therapy for newly diagnosed children; therefore, it will not be replacing frontline chemotherapy just yet.

Are there any other regimens in the pipeline that are showing a similar impact?

It is better to have relapsed ALL now rather than 10 years ago, because there is a whole class of immunotherapy drugs that are altering the treatment paradigm.

Targeted therapy and immunotherapy is giving us a much bigger armamentarium for patients with relapsed ALL. 

Which ongoing trials are you anticipating the results of?

The CAR T trials are still ongoing. They will begin to look at some specific populations to give this treatment earlier, such as infants with ALL and patients with Down syndrome.

The inotuzumab ozogamicin trial is the first pediatric trial in the United States that is open and enrolling through the Children’s Oncology Group right now. The first relapsed disease trial through the Children’s Oncology Group is studying blinatumomab. The study is looking at blinatumomab replacing blocks of chemotherapy as it is less toxic.

Those are some trials for targeted therapy, but there are many ongoing trials looking at different types of pediatric cancer. Since all trials will have a cohort of patients with ALL or acute myeloid leukemia, the investigators of the trials are interested in seeing what will lead to a better response or we can target something specifically.

Currently, what are the most pressing unmet needs for pediatric patients with ALL?

For ALL, we need more treatments for patients under 1 year old, who mostly have a specific subtype of cancer that is difficult to treat. These patients have a 50% outcome and the younger the patient, the worse the outcome. If a patient is less than 3 months old, they have less than a 20% survival rate.

There is a group of patients with relapsed ALL where CAR T-cell therapy does not work. CAR T-cell therapy, inotuzumab, and blinatumomab attack B-cell ALL, which makes patients with the T-cell ALL difficult to treat. We can cure 90% of those patients, but if they relapse after initial therapy, it is a challenge. T-cell ALL and infant ALL are 2 very challenging subtypes.

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