LaQuisa C. Hill, MD, on Relapsed or Refractory T-ALL: New Data on CD5 CAR T Cells
2023 ASCO Annual Meeting
LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston Methodist Hospital, discusses study findings showing that CD5 chimeric antigen receptor (CAR) T cells may induce clinical responses in heavily treated patients with relapsed or refractory T-cell acute lymphoblastic leukemia. Manufacturing CD5 CAR T cells with tyrosine kinase inhibitors seemed to improve their potency and antitumor activity (Abstract 7002).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
LaQuisa C. Hill, MD:
The purpose of this study was a phase one clinical trial that was a dose escalation study using autologous CD5 CAR T for treatment of patients with relapse/ refractory T-cell ALL. In the initial cohort, we used our standard manufacturing practice that was overall very well-tolerated. However, in the eight patients initially treated, there were minimal responses seen with only one patient achieving a MRD positive remission.
We subsequently analyzed the cell products and determined that the CAR T cells had a significantly exhausted phenotype as a result of chronic CAR signaling. Therefore, we implemented a manufacturing change to include the use of TKI inhibitors dasatinib and ibrutinib in order to inhibit the chronic CAR signaling and saw a significant improvement in the naive T-cell repertoire and significant reduction in the number of exhausted T-cells in the final product. In the next cohort, we treated a total of seven patients, all manufactured using the TKI inhibition. And amongst those patients there was a total of four MRD negative remissions achieved out of seven patients treated.
The CAR T cell was well-tolerated in terms of CRS and ICANS. No grade-three events occurred. However, there was an increased risk of, or observation of, EBV reactivation with two patients developing PTLD. Currently it is unclear of the direct relationship to the CD5 CAR T cells manufactured with TKI. However, we plan to continue vigilant monitoring for this unexpected side effect and have instituted mitigation plans utilizing prophylactic rituximab as well as ensuring that patients have EBV-specific virus T cells available in the event that EBV reactivation occurs.
Moving forward, we will continue to try and optimize the CAR T cell product both for efficacy and safety and are looking into alternative immune effector subsets, such as virus-specific T cells as the immune factor cell of choice, as well as considering use of third-party or off-the-shelf T cells from healthy donors.
The ASCO Post Staff
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ticiana Leal, MD, of Winship Cancer Institute of Emory University, discuss the use of tumor treating fields therapy, in which electric fields disrupt processes critical for cancer cell viability. Already approved by the FDA to treat glioblastoma and mesothelioma, the treatment has extended overall survival in this phase III study of patients with metastatic non–small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, without exacerbating systemic toxicities (Abstract LBA9005).
The ASCO Post Staff
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, and Gregory Roloff, MD, of the University of Chicago, discuss data that are the first to demonstrate post–FDA approval efficacy and toxicity rates of brexucabtagene autoleucel in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Although the data may confirm high response rates associated with this agent, they also highlight the need for interventions to reduce associated toxicities (Abstract 7001).
The ASCO Post Staff
Paula Aristizabal, MD, MAS, of the University of California, San Diego, and Rady Children’s Hospital, talks about using a health systems strengthening approach to improve leukemia care and survival in a public Mexican hospital in the region of the border between the United States and Mexico. The demonstrated increase in overall survival across a decade after implementation of the program seems to validate the use of such models, not only to improve clinical outcomes, but also to build sustainable hospital capacity, financially and organizationally (Abstract 1502).
The ASCO Post Staff
Funda Meric-Bernstam, MD, of The University of Texas MD Anderson Cancer Center, discusses interim results from the DESTINY-PanTumor02 trial, the first tumor-agnostic global study of fam-trastuzumab deruxtecan-nxki (T-DXd) in a broad range of HER2-expressing solid tumors. This agent showed an encouraging overall response rate, particularly in patients with IHC 3+ expression; durable clinical benefit; and a manageable safety profile in these heavily pretreated patients. T-DXd may be a potential new treatment option for this population (Abstract LBA3000).
The ASCO Post Staff
Rana R. McKay, MD, of the University of California, San Diego, and Toni K. Choueiri, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discuss results from the phase III CONTACT-03 study, showing that, for patients with metastatic renal cell carcinoma (RCC), adding the PD-L1 inhibitor atezolizumab to cabozantinib did not improve clinical outcomes compared with treatment with cabozantinib alone. In addition, higher toxicities were observed in the combination arm (Abstract LBA4500).
