CAR T-Cell Immunotherapy Induces Finish Remissions in Patients with Refractory DLBCL

• Date: nine Dec 2016
• Topic: Haematologic malignancies / Cancer Immunology and Immunotherapy

A late violating abstract introduced during the 58th American Society of Haematology (ASH) Annual Meeting and Exposition in San Diego, US (3-6 December, 2016) demonstrates that chimeric antigen receptor (CAR) T-cell therapy is a promising option for treatment of refractory diffuse large B-cell lymphoma(DLBCL). From a practice perspective, it could be implemented in a diversity of real-world clinical settings. The probe, which involved twenty two institutions and tested anti-CD19 CAR T-cells, is the very first multicentre trial of this cellular immunotherapy-based treatment treatment for lymphoma.

The examine focused on patients with DLBCL that does not react to chemotherapy or recurs after autologous stem cell transplant. Such chemorefractory patients have a poor prognosis; median overall survival is just over six months and only about 8% achieve finish remission with existing therapies. There has been no fresh treatment for these patients for over twenty years.

In the very first phase of ZUMA-1 investigate, which was conducted in four institutions, 43% of patients have ongoing finish remission at twelve months. To test the treatment’s real-world feasibility, the 2nd phase of ZUMA-1 expanded the probe to involve twenty two institutions, most of which had no prior practice with CAR T-cell therapy.

The fresh findings report positive results from a pre-specified interim analysis of fifty one patients with DLBCL. Following anti-CD19 CAR T-cell treatment, these patients had an overall response rate of 76% (47% finish remission and 29% partial remission) with most responses noted within the very first month. By the end of month three, the overall remission rate was 39% (33% finish remission and 6% partial remission).

According to the researchers, led by Dr Sattva Neelapu of The University of Texas MD Anderson Cancer Center in Houston, the results are encouraging from an efficacy standpoint and also display that CAR T-cell manufacturing, treatment logistics, and the management of adverse events can be successfully implemented across numerous sites.

Serious adverse events reported in the total DLBCL cohort of seventy three patients that were related to anti-CD19 CAR T-cells included neurologic events (25% of patients; typically improvised confusion or disorientation) and grade three or higher cytokine release syndrome (14%). The most common symptoms of cytokine release syndrome were fever, hypotension, and dyspnoea. The researchers reported that one patient died as a result of overactivation of the immune system.

Latest studies of CAR T-cell therapy have improved the capability to manage side effects. There are now guidelines on how to recognise and grade these side effects and how to manage the symptoms.

The team has also separately analysed results from twenty patients in ZUMA-1’s 2nd cohort, which include patients with primary mediastinal B-cell lymphoma or transformed follicular lymphoma, two lymphoma types that are less common than DLBCL. The overall response rate in this 2nd cohort is 80% with a accomplish remission rate of 55%.

The researchers will proceed to track patient outcomes in these cohorts for fifteen years.

LBA-6. Neelapu SS, Locke FL, Bartlett NL, et al. Kte-C19 (anti-CD19 CAR T Cells) Induces Finish Remissions in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Results from the Pivotal Phase two ZUMA-1. Introduced at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego, US (3-6 December 2016).

998. Locke FL, Neelapu SS, Bartlett NL, et al. A Phase two Multicenter Trial of KTE-C19 (anti-CD19 CAR T Cells) in Patients With Chemorefractory Primary Mediastinal B-Cell Lymphoma (PMBCL) and Transformed Follicular Lymphoma (TFL): Interim Results From ZUMA-1. Introduced at the 58th American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego, US (3-6 December 2016).

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