New analysis of trial data on Novartis’ CAR-T therapy Kymriah presented at the 59th American Society of Hematology (ASH) annual meeting show that the drug sustained complete responses at six months in adults with a difficult to treat form of blood cancer.
CAR-T offers a new treatment approach in that it is specifically manufactured for each individual patient. During the process, T cells are drawn from a patient's blood and reprogrammed in the lab to create T cells that are genetically coded to hunt the patient's cancer cells.
Data from the Juliet trial, which was led by researchers from the University of Pennsylvania (Penn), show an overall response rate (ORR) of 53 percent in patients taking Kymriah (tisagenlecleucel), with 40 percent achieving a complete response (CR) and 14 percent achieving a partial response (PR).
At six months, 30 percent of patients were in complete response, with a 74 percent relapse-free rate after onset of response, while median duration of response was not reached.
“At the time of trial enrollment, these patients with DLBCL had been through multiple rounds of chemotherapy and many had unsuccessful stem cell transplants, leaving them with few options and a poor prognosis,” said the study’s principal investigator Stephen J. Schuster, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in Penn’s Perelman School of Medicine and director of the Lymphoma Program at the Abramson Cancer Center.
“With tisagenlecleucel, we have been able to significantly increase their chance of achieving and maintaining a sustained response without stem cell transplant, demonstrating the therapy’s benefit in the treatment of this lethal blood cancer.”
On the safety side, cytokine release syndrome (CRS) – which can occur when engineered cells become activated in the patient's body - occurred in 58 percent of all treated patients, with 23 percent of patients experiencing grade 3/4 CRS.
Twenty-one percent of patients experienced any grade neurologic events, and 12 percent of patients had grade 3/4 neurologic adverse events, which were managed with supportive care. Grade 3/4 cytopenias lasting more than 28 days, grade 3/4 infections and grade 3/4 febrile neutropenia occurred in 27 percent, 20 percent and 13 percent of patients, respectively.
“While immediate response to treatment is a marker for efficacy, patients and physicians need treatment options that provide sustained responses over time with a consistent safety profile,” noted Samit Hirawat, head, Novartis Oncology Global Drug Development. “We look forward to continuing to work with health authorities to bring Kymriah to patients with relapsed or refractory DLBCL.”
The data were included in the US and EU regulatory filings for Kymriah in the r/r DLBCL setting, Novartis noted.
Last month the drugmaker filed tisagenlecleucel with the European Medicines Agency seeking permission to market its cell therapy to treat children and young adults with relapsed or refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL) and for adult patients with r/r DLBCL who are ineligible for autologous stem cell transplant.
In August Kymriah became the first ever CAR-T cell therapy to win approval in the US for paediatric and young adult patients with B-cell acute lymphoblastic leukaemia.