Latest news with #large_B_cell_lymphoma
Medscape
a day ago
- Health
- Medscape
Lymphoma: Dual-Targeting CAR T Shows Safety, Efficacy
In a first in-human study, KITE-363, an anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy, showed high rates of response in patients with highly refractory large B-cell lymphoma (LBCL). The bicistronic, autologous CAR T-cell therapy, designed to prevent CD19 escape through the upfront targeting of CD19 and CD20, also showed an encouraging safety profile, with no dose-limiting toxicities. METHODOLOGY: The phase 1, open-label, multicenter study enrolled adult patients with LBCL, indolent non-Hodgkin lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, or mediastinal gray zone lymphoma. Following lymphodepleting chemotherapy, patients were treated with KITE-363 at dose levels of 1, 2, or 3, corresponding to 0.5 × 10 6 , 1 × 10 6 , and 2 × 10 6 CAR T cells per kilogram, respectively. , 1 × 10 , and 2 × 10 CAR T cells per kilogram, respectively. Among 37 patients who were eligible and treated, the majority (73%) had advanced stage III or IV disease, and all were highly refractory, with more than two prior lines of therapy. The median age of patients was 62 years, with more than 10% of those in the study older than 75 years. TAKEAWAY: At a median follow-up of 11.2 months, the outcomes for CAR T-naive patients treated at dose level 3 (n = 23; 2 × 10 6 CAR T cells per kilogram), which is the recommended dose for phase 2 trials, showed an overall response rate (ORR) of 87%, while the complete response (CR) rate was 78%. CAR T cells per kilogram), which is the recommended dose for phase 2 trials, showed an overall response rate (ORR) of 87%, while the complete response (CR) rate was 78%. All seven patients (100%) with LBCL who were CAR T-naive after two or more lines of therapy and who received dose level 3 had a CR. Of the 15 patients receiving dose level 3 who were primary refractory, the ORR was 80% and the CR rate was 67%. The median duration of CR was not reached, while the 6-month duration of CR was 71.4%. Overall, no dose-limiting toxicities occurred. There were no grade 3 or higher reports of cytokine release syndrome (CRS). Two cases of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred with short durations; however, no cases occurred among those receiving dose level 3, with primary refractory LBCL (n = 15). IN PRACTICE: 'KITE-363 demonstrated high responses in patients with highly refractory LBCL, including those with primary refractory disease,' said first author Saurabh Dahiya, MD, of the Stanford University School of Medicine, in Stanford, California. 'We observed no grade 3 or 4 CRS or ICANS in this study, which is a sharp contrast to the current FDA-approved CAR T-cell therapies,' he said. 'Taken together, these results support KITE-363 as a promising therapeutic approach for patients with R/R [relapsed or refractory] B-cell lymphoma, including those with highly refractory LBCL,' Dahiya added. 'Given the promising early results and specifically robust CAR T expansion and good safety profile, KITE-363 is now being developed for the treatment of autoimmune conditions.' SOURCE: This study was presented in Chicago at American Society of Clinical Oncology (ASCO) 2025. DISCLOSURES: This study was funded by Kite, a Gilead Company.
Medscape
07-05-2025
- Health
- Medscape
Lymphoma: Muscle Mass May Presage CAR T Outcomes
Sarcopenia, a hallmark of cancer cachexia, is associated with poor outcomes in chimeric antigen receptor (CAR) T-cell therapy, which can exacerbate muscle loss through inflammatory responses. The relationship between CAR T-cell therapy, sarcopenia, and metabolism requires further investigation to improve patient outcomes. METHODOLOGY: Researchers measured skeletal muscle index from clinical images in 83 patients with large B-cell lymphoma at baseline and days 30 and 90 post-therapy. Serum metabolomics analysis was performed in 57 patients during the first 4 weeks. Patients received axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel in a standard-of-care setting at Moffitt Cancer Center between December 2017 and March 2022. Analysis included measurement of tissue cross-sectional areas using SliceOmatic software on abdominal CT images at mid-L3 vertebra level, with assessors blinded to imaging timing. TAKEAWAY: Baseline sarcopenia was present in over half of patients and linked to shorter median overall survival compared with nonsarcopenic patients (10.5 vs 34.3 months; P = .006). = .006). All six nonrelapse mortality events occurred in patients with baseline sarcopenia. One third of patients experienced > 10% skeletal muscle loss in the first 30 days after CAR T-cell therapy, associated with higher tumor burden and neurotoxicity. Serum metabolomics revealed early increases in purine metabolites (weeks 1-2), followed by later increases in triglyceride levels (weeks 3-4). IN PRACTICE: 'CAR T-cell therapy is associated with fatty acid catabolism and skeletal muscle loss is common. Patients with baseline sarcopenia have poor tolerance. Strategies focusing on diet, exercise, and/or fatty acid metabolism are warranted to attempt to improve patient outcomes,' the authors of the study wrote. SOURCE: This study was led by Khushali Jhaveri, MD, Moffitt Cancer Center, Tampa, Florida, and Neeraj Saini, MD, of The University of Texas MD Anderson Cancer Center, Houston. It was published in Clinical Cancer Research (AACR Journals) in April. LIMITATIONS: The retrospective single-center design and small sample size may have limited the power and generalizability of the findings. While precision error in measuring skeletal muscle using abdominal CT scans exists, images were assessed while blinded to their timing and significant muscle loss was defined as ≥ 10%, well beyond established precision error estimates. Analysis of muscle loss over time, particularly at day 90, was affected by bias from patient exclusions due to competing risks, as patients with progressive disease before day 90 were excluded due to lack of imaging. DISCLOSURES: Saini reported receiving research funding from Panbela Therapeutics. Michael D. Jain disclosed receiving consultancy/advisory roles for Kite/Gilead, Novartis, and Myeloid Therapeutics, along with research funding from Kite/Gilead, Incyte, and Loxo@ Lilly. Additional disclosures are noted in the original article.
