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
Sebastian Stintzing, MD, of the Charité Universitätsmedizin Berlin, discusses results from the phase III FIRE-4 study, which showed that liquid biopsy is clinically relevant in verifying mutational status in patients with metastatic colorectal cancer and is efficacious in first-line treatment of FOLFIRI and cetuximab for patients with RAS wild-type disease (Abstract 3507).
The ASCO Post Staff
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
The ASCO Post Staff
Alberto Bossi, MD, of Institut Gustave Roussy, discusses phase III findings showing that combining prostate radiotherapy with systemic treatment did not improve overall survival in men with de novo metastatic castration-sensitive prostate cancer and low metastatic burden. However, best outcomes (radiographic progression–free-survival and overall survival) were observed in men receiving the standard of care plus abiraterone acetate plus prednisone with radiotherapy (Abstract LBA5000).
The ASCO Post Staff
Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss findings from the POLARIX study, which provided the largest prospectively collected circulating tumor DNA (ctDNA) data set on patients with previously untreated diffuse large B-cell lymphoma. Achieving ctDNA-negative status was associated with improved outcomes when patients were treated with polatuzumab vedotin-piiq plus combination chemotherapy vs combination chemotherapy alone (Abstract 7523).
The ASCO Post Staff
Claire Roddie, PhD, MBChB, of University College London, discusses results of the FELIX study, which showed that the second-generation chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel is safe for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, even those with a high burden of disease. This agent yielded high rates of complete response and ongoing CAR T-cell persistence in most patients whose disease responded (Abstract 7000).
