Tisagenlecleucel ‘can be curative’ for some children with acute leukemia
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Key takeaways:
- Tisagenlecleucel is increasingly used as earlier treatment for younger patients with B-cell acute lymphoblastic leukemia.
- Use of hematopoietic stem cell transplantation has decreased over the same time.
Children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia increasingly receive tisagenlecleucel in earlier settings when they have lower disease burden, according to findings presented at ASCO Annual Meeting.
Consequently, use of hematopoietic stem cell transplantation has declined in the patient population — including vulnerable groups, such as children aged less than 3 years, those with Down syndrome and those with isolated central nervous system disease.
“The ability to have an option for patients who, not too long ago, we would say, ‘The only way to give you a potential for long-term care is a bone marrow transplant or stem cell transplant’ is really a game changer in the field,” Rayne H. Rouce, MD, associate professor and associate director of community engagement in the office of diversity at Baylor College of Medicine, and member of the bone marrow transplant/stem cell transplant program at Texas Children’s Hospital, told Healio. “We have clearly shown that this therapy can be curative for some patients.”
Background and methods
Tisagenlecleucel (Kymriah, Novartis), often called tisa-cel, is a CD19-directed chimeric antigen receptor T-cell therapy. It is approved in the U.S. for three indications, including treatment of patients aged 25 years or younger with relapsed or refractory ALL.
Hematopoietic stem cell transplantation (HSCT) has been the standard of care for this population; however, this “very intensive” therapy requires a proper donor and usually a month-long hospital stay because patients need total body irradiation, Rouce said.
Adverse events associated with HSCT include infertility, slower growth, impaired cognitive development and graft versus host disease.
Rouce and colleagues conducted a prospective, longitudinal study to evaluate outcomes, safety and treatment patterns of tisa-cel for B-ALL since the FDA approved that indication in 2017.
They used the Center for International Blood and Marrow Transplant Research registry to identify 974 patients (70.5% aged younger than 18 years; 7.7% aged younger than 3 years) with B-ALL who received tisa-cel in the U.S., Canada, Korea or Taiwan.
Researchers established an efficacy cohort (n = 785) and safety cohort (n = 911).
Results and next steps
Researchers first analyzed tisa-cel based on disease burden, defined as low (> 0% to < 5% bone marrow blasts), intermediate ( 5% to < 50%) or high ( 50%).
The percentage of patients with low disease burden at the time of tisa-cel infusion increased from 16.7% in 2017 to 18.2% in 2023.
The percentage with intermediate disease burden at infusion increased from 8.3% to 12.1% during that time.
In contrast, the percentage of patients with high disease burden at tisa-cel infusion declined from 8.3% in 2017 to 6.1% in 2023.
The percentage of patients who received HSCT before tisa-cel infusion declined from 33.3% in 2017 to 6.1% in 2023. The number of patients in third or greater relapse at the time of tisa-cel infusion also decreased.
“We were a bit surprised about the overwhelming trend of earlier use [for] patients who’ve been less heavily pretreated,” Rouce said. “[This] highlights the fact that people are recognizing that [for] some patients, it’s not necessary to have three, four [or] five different lines of therapy — especially when they’re chemotherapy alone. Switching to an immunotherapy like tisa-cel earlier may be beneficial.”
From 2018 to 2022, use of HSCT after tisa-cel decreased by 22 percentage points among children aged younger than 3 years, 7 percentage points among those aged 3 years to 17 years, and 5 percentage points among those aged least 18 years.
Median OS and RFS did not “substantially” differ among patients who received post-infusion HSCT and those who did not, Rouce said.
She described tisa-cel’s safety profile as “very consistent” with initial studies and called the long-term outlook “favorable across age groups.”
Patients who have a higher disease burden are more likely to develop cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS), Rouce said. This supports the benefit of treating children and young adults when disease burden is low, even if they are considered to be in remission.
“This therapy can still be effective when you have a tiny amount of disease, when you have very aggressive disease but have none at the time that you're treated, and [for] patients who have a higher disease burden,” Rouce said.
However, 40% to 60% of patients who receive tisa-cel relapse after initial response, Rouce said.
“A lot of [research] is looking at the algorithms of prediction of who this therapy is best for, mechanisms to prevent relapse, or other alternative mechanisms to treat in the case of a relapse and how to predict that,” Rouce said.
Clinicians should take a personalized approach to determine which treatment is best for each patient, Rouce said.
“Let’s actually look at the data on a larger scale and see if there are patients we can identify [who] are at higher risk for relapse after tisa-cel,” Rouce said. “Those are the ones we recommend transplant for.”
For more information:
Rayne H. Rouce, MD, can be reached at rhrouce@texaschildrens.org.
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Rouce RH, et al. Abstract 10016. Presented at: ASCO Annual Meeting; May 31-June 4, 2024; Chicago.
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