ASCO 2022: CAR T for Prostate Cancer: Current Strategies to Improve Efficacy

( In her portion of this case-based panel, Dr. Dorff described chimeric antigen receptor T-cell (CAR-T) therapy and its potential use in prostate cancer. She indicated that CAR-Ts are especially exciting given their potential to induce long-term disease responses, such as have been seen in leukemias and lymphomas. CAR-T cells are a flexible platform, where in addition to introducing a chimeric receptor against a tumor antigen into T-cells, they can be engineered to have immune-co-stimulatory domains and even secrete cytokines to help support T-cell proliferation. Future generations of CARs may also have a conditional expression or be able to be targeted against multiple tumor antigens.


ASCO 22_Tanya B. Dorff, MD_0 


After this introduction, Dr. Dorff focused her discussion on two clinical trials of CAR-T therapy in prostate cancer that have already read-out initial data. The first is a trial of the Poseida P-PSMA 101 therapy, which was initially presented at ASCO GU 2022. The features of this therapy are shown in the slide below, and include selection for a more-stem cell like T-cell population in case this allows for longer cell survival, and a Cas9 based safety switch.


ASCO 22_Tanya B. Dorff, MD_1 


The presented data included 14 patients with mCRPC, 79% of whom had received prior taxane and 43% who had received prior radium-223. Two patients had previously been enrolled on a PSMA BiTE therapy trial. Eight patients sustained symptoms of CRS, only two of which were grade 3 or higher. The swimmer’s plot presented below indicates that one patient has had ongoing PSA response accompanied by PSMA-PET decreased avidity.


ASCO 22_Tanya B. Dorff, MD_2 


Dr. Dorff then discussed data from a trial initially presented at ASCO GU 2022 of a CAR-T therapy targeting the prostate-stem cell antigen (PSCA). This antigen is expressed in 80% of primary prostate cancers, 90% of metastatic prostate cancers, as well as in the pancreas and bladder. In the 12 patients presented on this trial, patients were treated with 100 million CAR-T cells with varying lymphodepletion (specifically omission of cyclophosphamide to limit risk of cystitis). In patients treated with lymphodepleting therapy, cases of stable disease and PSA response have been observed, but CAR-T persistence in circulation is not optimal beyond day 28 after infusion.


One potential side effect of CAR-T therapy is an immune syndrome similar to macrophage activation syndrome/hemophagocytic lymphohistiocytosis. This is characterized by fever and elevated inflammatory markers, and can be managed with multiple agents such as steroids, ocilizumab or anakinra.


ASCO 22_Tanya B. Dorff, MD_3 


Presented by: Tanya B. Dorff, MD, City of Hope Comprehensive Cancer Center


Written by: Alok K. Tewari, MD, PhD, medical oncologist at the Dana-Farber Cancer Institute, @aloktewar on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.