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
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings showing that for patients with advanced or metastatic urothelial carcinoma and FGFR alteration who already had been treated with a PD-(L)1 inhibitor, erdafitinib significantly improved overall and progression-free survival, as well as overall response rate, compared with investigator’s choice of chemotherapy (LBA4619).
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
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
Tycel J. Phillips, MD, of City of Hope National Medical Center, and Emanuele Zucca, MD, of the Oncology Institute of Southern Switzerland and the International Extranodal Lymphoma Study Group, discuss findings from the largest prospective study of patients with primary mediastinal B-cell lymphoma. The trial data support omitting radiotherapy in patients who achieve complete metabolic response after immunochemotherapy (Abstract LBA7505).
The ASCO Post Staff
Enrique Grande, MD, of The University of Texas MD Anderson Cancer Center, discusses new findings that show initial responses to induction therapy with atezolizumab plus platinum and gemcitabine did not seem to impact overall survival for patients with metastatic urothelial carcinoma. Cisplatin-treated patients appeared to derive a greater benefit with atezolizumab than did carboplatin-treated patients (Abstract 4503).
