'Great News': CAR T Cells Are Effective and Safe in Babies

Roxanne Nelson, RN, BSN

December 09, 2019

ORLANDO, Florida ― Chimeric antigen receptor (CAR) T-cell therapy has been hailed as "truly a game changer for pediatric leukemia," and new data show that this novel therapy can be used even in the smallest of patients ― in 1-year-old babies.

The results come from a small cohort of infants with relapsed or refractory KMT2A-rearranged infant B-cell acute lymphoblastic leukemia (ALL). Of the 16 patients who were treated, 71.4% remain leukemia free at 1 year. Overall survival is 73.3%.

Dr Colleen Annesley

The CAR T-cell therapies were as effective for younger patients as has been observed for older children, and there was no increase in toxicities as compared to older patients. Thus, despite theoretical concerns that infants may not do as well or greater safety concerns with infants, "that hasn't been our experience," commented lead author Colleen Annesley, MD, an attending physician at Seattle Children's Hospital and an assistant professor in the Department of Pediatrics at the University of Washington, Seattle. "It's great news."

The study was presented here at American Society of Hematology (ASH) 2019.

"We know that babies do poorly with leukemia, and those that relapse have a dismal chance of survival," Annesley told Medscape Medical News. For infants with relapsed ALL, the reported 3-year overall survival rate is about 21%.

"We thought that CAR T cells could salvage some of them, but there were a lot of concerns about using them in this population," she commented.

Infants present unique challenges in comparison with older patients. Smaller patient size, heavily pretreated disease, and high leukemia burden are characteristic of these patients, and these factors can make apheresis and the manufacture of a T-cell product more difficult.

There were logistical concerns regarding the manufacturing a CAR T-cell product because the patients were so small, Annesley pointed out. "When they relapse, they may have a large burden of disease, and it can be difficult to get an apheresis catheter into them."

Another potential concern was lineage switching. "The leukemia changes from what looks like ALL to acute myeloid leukemia," said Annesley. "It's the nature of this rearrangement. The leukemia cells are prone to switch over under pressure, and in this case, there are reports of it occurring following CD19-targeting pressure."

Effective and Safe

Annesley and colleagued reported on their experience with CAR T-cell immunotherapy for patients with relapsed/refractory infant ALL who were enrolled in clinical trials PLAT-02 and PLAT-05.

PLAT-02 is a phase 1/2 trial of CD19-specific CAR T cells; PLAT-05 is a phase 1 trial of CD19 x CD22 dual specific CAR T cells, which are transduced with two separate lentiviral vectors to direct the coexpression of the CD19-specific CAR above and a CD22-specific CAR.

A total of 18 patients were enrolled (14 in PLAT-02, and four in PLAT-05). All of the patients were diagnosed before age 1 year. At the time they received CAR T-cell therapy, the median age was 20.6 months (range, 14–40 months). Almost half of the cohort (44.4%) had experienced one relapse; one patient had experienced more than three relapses; and 50% had already undergone stem cell transplant.

Successful CAR T-cell products were manufactured for 17 of the 18 patients. These included all nine patients who had not received a previous transplant. One patient died of disease complications prior to infusion. The remaining 16 received CAR T-cell therapy.

Of this group, 15 (93.8%) patients achieved minimal residual disease negative complete remission (MRD-CR) by day 21. One patient (6.2%) had progressive disease. The median duration of CAR T-cell persistence was 30.4 months.

Among those who achieved MRD-CR, seven patients proceeded to undergo stem cell transplant. "That is a controversy as to whether or not these patients need a consolidative transplant after CAR-T, and we're not answering that question with this abstract," Annesley explained. "But of those seven patients, six are in remission."

The remaining eight patients were placed under a "watch and wait" protocol. One died of unrelated causes, and four are in remission. Two other patients experienced a CD19+ relapse.

Toxicity was considered to be acceptable. Cytokine release syndrome of a maximum of grade 3 occurred in two patients. Neurotoxicity of a maximum of grade 2 was well managed with supportive care. "We found that the babies tolerated the therapy as well as older children and adolescents, which was good news," she said.

Currently, 10 patients remain in remission. "The study is small, but we're hopeful," said Annesley, "They seem to be doing better than treatment with traditional chemotherapy."

One of the patients did have lineage switch, but Annesley pointed out that they have observed patients without infant ALL and without this genetic rearrangement who have had lineage switch. "So in our experience, there hasn't been an increased risk of that, but we will continue to watch for it," she added.

The study was supported in part by the Ben Towne Foundation and the William and Blanche Hughes Foundation. Additional support was provided by the St. Baldrick's Foundation – Stand Up 2 Cancer and Alex's Lemonade Stand. Annesley has disclosed no relevant financial relationships; several coauthors have disclosed relationships with industry.

American Society of Hematology (ASH) 2019: Abstract 3869. Presented December 9, 2019.

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