Prophylactic Tocilizumab in Patients with Relapsed Refractory Lymphoma Treated with Anti CD19 Chimeric Antigen Receptor T-Cell Therapy

Abstract

IntroductionAnti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed and refractory aggressive lymphomas. Cytokine release syndrome (CRS) is a well-known complication of CAR-T cell therapy. Tocilizumab, a humanized monoclonal antibody targeting the interleukin 6 receptor, is approved for treatment of CRS. Our institutional standard has been recently modified to prescribe tocilizumab prophylaxis prior to CAR-T cell infusion. We present a retrospective review of the outcomes of subjects treated with and without prophylactic tocilizumab (PT).MethodsRelapsed / refractory (r/r) lymphoma treated with anti-CD19 CAR-T cells at our institution were included. Baseline demographic and clinical characteristics, as well as laboratory results were obtained from our Hematologic Malignancies and Stem Cell Therapy Database. Prior to institution of prophylactic tocilizumab, patients received this agent only if they presented evidence of CRS grade 2 or higher. In May 2019, our institutional practice changed to provide PT 8mg/kg, 1 hour prior to infusion of CAR-T cell product. CRS was measured according to the ASTCT Consensus Grading. Positron Emission Tests (PET) scans were done to assess response on Day 30. CART cell vector Persistence was measured using PCR and was done at different time points including Day 30.ResultsFourteen relapsed / refractory lymphoma pts were treated with antiCD19 CAR-T cells; 6 pts received prophylactic tocilizumab. Median follow up was 149 days. CAR-T cells dose was 0.5 × 106 CAR-T cells/Kg dose in 4 pts, while 10 pts received 1 × 106/kg CAR-T. Baseline characteristics are listed in table 1.Both groups were similar. There were no differences in the rate of bulky disease, prior ASCT or number or prior lines of therapy. Baseline lymphocyte counts, C – reactive protein (CRP) and ferritin were also comparable between groups (Table 2). CRS of any grade was observed in 6/8 (75%) of patients without PT vs. 1/6 (17%) in patients treated with PT (p = 0.05). There was a statistically significant difference in the peak CRP, with patients receiving PT having a CRP peak of 0.74mg/dl vs. 15.3mg/dl in patients without PT. Complete response was observed in 5/8 (63%) pts without PT vs. 4/5 patients with PT. All patients had detectable Anti-CD19 CAR-T cells on day 30.ConclusionsOur findings suggest prophylactic tocilizumab is associated with reduced incidence of CRS. This decreased rate of CRS is not associated with impaired disease control and response rates are comparable with those previously reported. Use of PT did not appear to affect CAR-T cell persistence. Subsequent studies should evaluate the optimal CRS prophylaxis schedule in patients treated with CAR-T cell therapies. Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed and refractory aggressive lymphomas. Cytokine release syndrome (CRS) is a well-known complication of CAR-T cell therapy. Tocilizumab, a humanized monoclonal antibody targeting the interleukin 6 receptor, is approved for treatment of CRS. Our institutional standard has been recently modified to prescribe tocilizumab prophylaxis prior to CAR-T cell infusion. We present a retrospective review of the outcomes of subjects treated with and without prophylactic tocilizumab (PT). Relapsed / refractory (r/r) lymphoma treated with anti-CD19 CAR-T cells at our institution were included. Baseline demographic and clinical characteristics, as well as laboratory results were obtained from our Hematologic Malignancies and Stem Cell Therapy Database. Prior to institution of prophylactic tocilizumab, patients received this agent only if they presented evidence of CRS grade 2 or higher. In May 2019, our institutional practice changed to provide PT 8mg/kg, 1 hour prior to infusion of CAR-T cell product. CRS was measured according to the ASTCT Consensus Grading. Positron Emission Tests (PET) scans were done to assess response on Day 30. CART cell vector Persistence was measured using PCR and was done at different time points including Day 30. Fourteen relapsed / refractory lymphoma pts were treated with antiCD19 CAR-T cells; 6 pts received prophylactic tocilizumab. Median follow up was 149 days. CAR-T cells dose was 0.5 × 106 CAR-T cells/Kg dose in 4 pts, while 10 pts received 1 × 106/kg CAR-T. Baseline characteristics are listed in table 1.Both groups were similar. There were no differences in the rate of bulky disease, prior ASCT or number or prior lines of therapy. Baseline lymphocyte counts, C – reactive protein (CRP) and ferritin were also comparable between groups (Table 2). CRS of any grade was observed in 6/8 (75%) of patients without PT vs. 1/6 (17%) in patients treated with PT (p = 0.05). There was a statistically significant difference in the peak CRP, with patients receiving PT having a CRP peak of 0.74mg/dl vs. 15.3mg/dl in patients without PT. Complete response was observed in 5/8 (63%) pts without PT vs. 4/5 patients with PT. All patients had detectable Anti-CD19 CAR-T cells on day 30. Our findings suggest prophylactic tocilizumab is associated with reduced incidence of CRS. This decreased rate of CRS is not associated with impaired disease control and response rates are comparable with those previously reported. Use of PT did not appear to affect CAR-T cell persistence. Subsequent studies should evaluate the optimal CRS prophylaxis schedule in patients treated with CAR-T cell therapies.