|The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Administration of a chimeric antigen receptor T-cell (CAR-T) therapy that targets both CD19 and CD22, followed by pembrolizumab, appeared to be safe and clinically active in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The initial results of the trial were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.
“The incorporation of dual targeting and anti–PD-1 to target relapses due to antigen loss and PD-L1 upregulation is novel and first in its kind,” the study authors wrote in the study abstract.
The construct independently targets CD19 and CD20, and is delivered in a single retroviral vector. Use of dual costimulatory domains, OX40 and 4-1BB, is thought to improve persistence.
In the single-arm, multicenter, open-label phase 1/2 trial, the CAR-T cell product, dubbed AUTO3, 27 patients were leukapheresed, and 23 had product successfully made for them. However, 7 of the patients with successfully manufactured product discontinued treatment, so product was successfully administered to 16. And of these 16 patients, 14 were deemed evaluable at the time of the presentation.
There were 3 doses of CAR-T explored in the latest update: 50×106 AUTO3, 150×106 AUTO3, and 450×106 AUTO3. Lymphodepleting therapy with fludarabine and cyclophosphamide was given to all patients before CAR-T infusion.
Among the patients who received CAR-T, the rate of any-grade cytokine release syndrome (CRS) was 31.3%.Overall, none of the patients had grade 3 or higher cytokine release syndrome (CRS), except for 1 patient. The lead researcher of the study, Dr Kirit M. Ardeshna, from the University College London Hospital NHS Foundation Trust, London, United Kingdom, noted the following: “One patient who had no CRS with primary infusion developed grade 3 CRS with retreatment 1 year later, which happened in a setting of no CAR-T expansion and significant disease burden in lung that had been treated with radiation.”
Only 1 patient received tocilizumab for CRS, there were no patients admitted to the intensive care unit (ICU) for CRS management, and there was only 1 instance of grade 3 neurotoxicity, which resolved quickly with steroid treatment. A serum cytokine profile in patients confirmed that there were low levels of cytokines present, which is consistent with lower-grade CRS.
A primary efficacy analysis across all dose cohorts revealed that 3 patients were deemed nonevaluable, 3 patients had a partial response, and 5 patients had a complete response (the other patients did not appear to have survival values yet, or the values were not yet marked on the presenter’s slide).
Four of the five complete responses (80%) were ongoing. In the lowest-dose cohort, one of the patients who initially had a complete response subsequently had progressive disease at follow-up.
In summary, the researchers noted that complete responses with dual-targeted CAR-T followed by pembrolizumab were seen “without severe CRS, neurotoxicity, or ICU care.”
Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.
Ardesha K, Marzolini M, Jane Norman J, et al. Phase 1/2 study of AUTO3 the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL): Results of cohort 1 and 2 of the Alexander study. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 246.