Axicabtagene ciloleucel CD19 CAR-T cell therapy results in high rates of systemic and neurologic remissions in ten patients with refractory large B cell lymphoma including two with HIV and viral hepatitis

Abstract

Axicabtagene ciloleucel (Axi-cel) is a CD-19 Chimeric Antigen Receptor T cell therapy approved for the treatment of relapsed/refractory diffuse large B cell lymphoma. We treated ten patients with DLBCL post-FDA approval in an inner-city tertiary center in the Bronx. Eight patients (80%) had received ≥ 3 lines of therapy, six patients had received prior radiation, and seven had recurrent disease after prior autologous hematopoietic stem cell transplant (AHCT). Our cohort included one patient with HIV, two patients with hepatitis B, and two patients with CNS involvement of lymphoma. Axi-cel treatment led to significant responses with 8/10 patients achieving a complete remission at 3 months, including both patients with prior CNS involvement. The treatment was generally well tolerated with 20% of patients experiencing grade ≥ 2 CRS. One patient each with HIV and hepatitis B responded without significant toxicities. In conclusion, Axi-cel led to significant efficacy with manageable toxicity in DLBCL in a real-world setting.

Chimeric antigen receptor T cells targeting PD-L1 suppress tumor growth

“…Recently, chimeric antigen receptor T cells (CAR-T cells) have emerged as a promising therapy for treating B cellderived malignancy [1,2]. Two CAR-T cell products have been approved by the FDA to treat B-cell leukemia and lymphoma [3][4][5][6]. CAR-T cells against tumor-specific antigens (TSA), including mesothelin (MSLN) and glypican 3 (GPC3) are being actively tested for treating nonsmall-cell lung cancer (NSCLC) and hepatocellular carcinoma, respectively [7][8][9][10][11][12][13][14][15][16][17][18][19].…”

Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper

“…The European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) practice recommendations have suggested that pharmaceutical companies could manufacture CAR T cells for HIV-positive patients if the viral load was undetectable after anti-retroviral treatment [54]. The published clinical experience is limited to three patients with HIV successfully treated with CAR T cells without additional toxicity [55,56].…”

Chimeric antigen receptor T cells targeting PD-L1 suppress tumor growth

“…To develop the lung cancer cell line xenograft models, 5×10 5 H460GL cells in 200 μl of PBS were injected subcutaneously into the right anks of NOD-SCID-IL2Rg-/-(NSI) mice aged 6-8 weeks. Ten days after tumor cell transplantation, 5×10 6 CAR T cells were injected through the tail vein of mice. Tumors were measured at indicated days with a caliper to determine the subcutaneous growth rate.…”

“…Then, 10, 15, 20 or 24 days after tumor transplantation, mice were infused with CAR T cell or control T cells. In total, 5×10 6 CAR T cells were injected one time into each mouse. Tumors were measured with a caliper, and tumor volume was calculated using the following equation: (length×width×width)/2.…”

“…Recently, chimeric antigen receptor T cells (CAR-T cells) have emerged as a promising therapy for treating B cell-derived malignancy [1,2]. Two CAR-T cell products have been approved by the FDA to treat B-cell leukemia and lymphoma [3][4][5][6]. CAR-T cells against tumor-speci c antigens (TSA), including mesothelin (MSLN) and glypican 3 (GPC3) are being actively tested for treating non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma, respectively [7][8][9][10][11][12][13][14][15][16][17][18][19].…”