treated with UCART19
Photo courtesy of GOSH
New research suggests that “universal,” donor-derived, chimeric antigen receptor (CAR) T cells may be a viable treatment option for very young children who do not have sufficient healthy T cells for autologous CAR T-cell therapy.
The universal CAR T-cell therapy, known as UCART19, was given to 2 infants with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) who had previously
exhausted all other treatment options.
Both infants achieved remission after UCART19 and were able to proceed to transplant.
Both were still alive and leukemia-free at last follow-up—12 months and 18 months after UCART19, respectively.
Waseem Qasim, MBBS, PhD, of University College London’s Institute of Child Health and Great Ormond Street Hospital (GOSH) in London, UK, and his colleagues reported these results in Science Translational Medicine.
About the therapy
UCART19 consists of donor T cells modified using transcription activator-like effector nucleases. The cells are programmed to target CD19 and be insensitive to alemtuzumab. That way, a patient can receive alemtuzumab to prevent rejection of HLA-mismatched cells.
UCART19 was under development by Cellectis but is now being developed by Servier and Pfizer Inc. Pfizer has exclusive rights to develop and commercialize UCART19 in the US, while Servier retains exclusive rights for all other countries.
In Science Translational Medicine, Dr Qasim and his colleagues reported results in the first patients ever treated with UCART19. That research was funded, in part, by Cellectis.
Subject 1
The first patient was an 11-month-old, mixed-race infant with high-risk, t(11;19), CD19+ B-ALL. She had already failed chemotherapy, an allogeneic hematopoietic stem cell transplant (HSCT), and blinatumomab.
Prior to UCART19, she received a dose of vincristine and asparaginase and 7 days of dexamethasone, followed by cytoreduction with fludarabine, cyclophosphamide, and alemtuzumab. She then received a single dose of UCART19 (4.6 × 106/kg).
The patient had neutrophil recovery by day 30, although this was dependent on granulocyte colony-stimulating factor. After that, she developed multilineage cytopenia that persisted until she underwent a second allogeneic HSCT.
Prior to the second HSCT, the patient achieved cytogenetic and molecular remission but also developed grade 2 skin graft-vs-host disease. This was managed with systemic steroids.
The child received rituximab and conditioning with antithymocyte globulin, fludarabine, cyclophosphamide, thiotepa, and total body irradiation, followed by an HSCT from the original mismatched, unrelated donor.
The child achieved a complete remission and has remained minimal residual disease-negative, with full donor chimerism and normalized lymphocyte profiles, at 18 months after UCART19.
Results with this patient were previously reported by GOSH in November 2015 and at the 2015 ASH Annual Meeting.
Subject 2
The second patient was a 16-month-old Caucasian infant who had been diagnosed at 4 weeks of age with high-risk, congenital, mixed lineage leukemia–rearranged B-ALL.
She had already undergone HSCT from a matched, unrelated donor but relapsed. She did not respond to subsequent blinatumomab.
After these failed treatments, the patient received fludarabine, cyclophosphamide, and alemtuzumab, followed by a single infusion of UCART19 (4.0 × 106/kg).
She developed an erythematous rash after treatment, but this was immediately responsive to topical steroids.
The child achieved donor-derived neutrophil recovery and went on to receive a transplant from the same matched, unrelated donor as her previous HSCT.
The child received the transplant within 10 weeks of UCART19 therapy, after receiving rituximab and conditioning with antithymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.
At 12 months after UCART19, the child remains minimal residual disease-negative and “clinically well.”
“Both infants who have had this treatment have been at home for some time and are doing well,” Dr Qasim said. “We continue to monitor them closely, and, while we have reduced the frequency of their hospital visits and checks, we will still need to keep an eye on them for some time.”
Dr Qasim added that there are phase 1 trials of UCART19 underway for children and adults with chronic lymphocytic leukemia and acute lymphoblastic leukemia.
