Novartis announced findings from a pilot study (NCT02640209) of CTL119 in combination with ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had been taking ibrutinib for at least six months and who were not in complete remission. All study patients had to have failed at least one prior regimen before ibrutinib or carried high-risk cytogenetics or mutations.
The results, which will be presented at the upcoming 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO; abstract #7509; Monday, June 5, 1:15 PM CDT), that eight of nine evaluable patients had no signs of CLL in their bone marrow at three months. One of those patients had a partial response.
"The data from this pilot study support the potential for CTL119, when combined with the kinase inhibitor ibrutinib, to induce clinically-significant responses in high-risk CLL patients who were unlikely to achieve a complete remission on ibrutinib alone," said James Bradner, president of the Novartis Institutes for BioMedical Research. "CTL119 represents one of our latest advances in CAR-T cell therapy research and our broader commitment to pioneering breakthrough immuno-oncology treatments."
The findings will be presented by Saar Gill, MD, PhD, an assistant professor of Hematology-Oncology in the Perelman School of Medicine and the Abramson Cancer Center of the University of Pennsylvania.
CTL119 is a humanized CD19-directed chimeric antigen receptor T cell (CAR-T) cell therapy, which is different from typical small molecule or biologic therapies because it is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient's blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient's cancer cells and other B-cells expressing a particular antigen.
Results from the pilot study also showed that eight of nine patients had no signs of CLL in their bone marrow at three months as tested by flow cytometry and/or analysis for minimal residual disease (MRD). MRD, which measures the presence of residual abnormalities in the blood and bone marrow at the molecular level following treatment, is important because it can be an indicator of potential relapse.
CT scans were performed to measure the inclusion of CLL in the spleens and lymph nodes of study patients. A number of patients showed improvements in the burden of disease in their spleens and lymph nodes at three months, though radiologic responses are less clear cut and they require longer follow-up.
In the study, 10 patients experienced cytokine release syndrome (CRS), two of which were grade 3. However, no patients required treatment with tocilizumab and all patients recovered from CRS. One patient developed tumor lysis syndrome and two patients had febrile neutropenia .
CLL is one of the most common types of adult leukemia, which typically progresses slowly over time. The majority of patients will relapse after initial therapy, and newer targeted therapies must be taken continuously for an indefinite period of time. These are clear indications of the high unmet medical need for new therapies for CLL.