The ATLAS study combines two different ways of fighting disease: antibodies and T-cells. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T-cells are special infection-fighting blood cells that can kill other cells. Both antibodies and T-cells have been used to treat cancer patients, but neither alone has been sufficient to cure most patients. This study is designed to combine both T-cells and antibodies to create a more effective treatment. The treatment being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30). The purpose of this trial is to determine a safe dose of the ATLCAR.CD30 cells that can be given to subjects after undergoing an autologous transplant.1
Chimeric antigen receptor (CAR) T-cells targeting CD30 are safe and have promising activity when preceded by lymphodepleting chemotherapy. The trial is to determine the safety of anti-CD30 CAR T-cells as consolidation after autologous haematopoietic stem-cell transplantation (HSCT) in patients with CD30+ lymphoma at high risk/relapse.2
Methods
This phase I dose-escalation study was performed at two sites in the United States. Patients aged ≥3 years, with classical Hodgkin lymphoma or non-Hodgkin lymphoma with CD30+ disease documented by immunohistochemistry, and a Karnofsky performance score of more than 60% planned for autologous HSCT were eligible if they were considered high-risk for relapse as defined by primary refractory disease or relapse within twelve months of initial therapy or extranodal involvement at the start of pre-transplantation salvage therapy. Patients received a single infusion of CAR T-cells (2 × 107 CAR T cells per m2, 1 × 108 CAR T-cells per m2, or 2 × 108 CAR T-cells per m2) as consolidation after trilineage haematopoietic engraftment (defined as absolute neutrophil count ≥500 cells per μL for three days, platelet count ≥25 × 109 platelets per L without transfusion for five days, and haemoglobin ≥8 g/dL without transfusion for five days) following carmustine, etoposide, cytarabine, and melphalan (BEAM) and HSCT. The primary endpoint was the determination of the maximum tolerated dose, which was based on the rate of dose-limiting toxicity in patients who received CAR T-cell infusion.
Findings
Between June 7th, 2016, and November 30th, 2020, 21 patients were enrolled and eighteen patients (eleven with Hodgkin lymphoma, six with T-cell lymphoma, one with grey zone lymphoma) were infused with anti-CD30 CAR T-cells at a median of 22 days (range 16–44) after autologous HSCT. There were no dose-limiting toxicities observed, so the highest dose tested, 2 × 108 CAR T-cells per m2, was determined to be the maximum tolerated dose. One patient had grade 1 cytokine release syndrome. The most common grade 3–4 adverse events were lymphopenia (two [11%] of 18) and leukopenia (two [11%] of 18). There were no treatment-related deaths. Two patients developed secondary malignancies approximately two years and 2.5 years following treatment (one stage 4 non-small cell lung cancer and one testicular cancer), but these were ruled as unrelated to treatment. At a median follow-up of 48.2 months (IQR 27.5–60.7) post-infusion, the median progression-free survival (PFS) for all treated patients (n=18) was 32.3 months (95% CI 4.6 months to not estimable) and the median PFS for treated patients with Hodgkin lymphoma (n=11) has not been reached. The median overall survival for all treated patients has not been reached.
Conclusion
Anti-CD30 CAR T-cell infusion as consolidation after BEAM and autologous HSCT is safe, with low rates of toxicity and encouraging preliminary activity in patients with Hodgkin lymphoma at high risk of relapse, highlighting the need for larger studies to confirm these findings.2
REFERENCES
1. ClinicalTrials.gov ID NCT02663297. Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Prevention of Relapse of CD30+ Lymphomas After High Dose Therapy and Autologous Stem Transplantation (ATLAS). Accessed on 20 June 2024.
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