Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B‐cell lymphoma

Abstract

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel-related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 9 10 6 anti-CD19 CAR T cells/kg after conditioning chemotherapy. Forty-one patients received axi-cel. Incidences of any-grade CRS and NEs were 93% and 61%, respectively (grade ≥ 3, 2% and 17%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone-equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA-1 cohorts. With a median follow-up of 14Á8 months, objective and complete response rates were 73% and 51%, respectively, and 51% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/ or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi-cel.

A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma

“…However, it is well-known that new mitigation strategies for CRS and ICANS management have led to much lower rates of severe CRS or ICANS. For instance, recent data on prospective evaluation of early use of dexamethasone after axi-cel infusion demonstrated 17% of grade ≥3 ICANS 26 . In the study from the German group, grade ≥3 ICANS was 16% for axi-cel, quite similar to our data, and 7% for tisa-cel, slightly higher than what is reported here 27 .…”

Cost-Effectiveness of Chimeric Antigen Receptor T Cell Therapy in Patients with Relapsed or Refractory Large B Cell Lymphoma: No Impact of Site of Care

“…In the base case, relevant axi-cel input values were based on ZUMA-1 cohorts 1 and 2. To examine the effect of alternative safety protocols adopted for more recent ZUMA-1 cohorts, scenario analyses were conducted using ZUMA-1 cohort 4 [ 30 ] and ZUMA-1 cohort 6 [ 31 ] to inform relevant axi-cel input values (Table S7 in the supplementary material). ZUMA-1 cohort 4 patients received earlier corticosteroids and/or tocilizumab in response to CRS and NE, while cohort 6 patients received prophylactic and earlier corticosteroids and/or tocilizumab for prevention/treatment of CRS and NE.…”

Early immunomodulators with CAR T-cell immunotherapy in the COVID-19 era

“…Although there were no grade 4 or worse toxic effects reported, grade 3 CRS and ICANS occurred at rates of 2% and 17%, respectively. 2 Despite earlier dosing, the cumulative corticosteroid dose in patients who needed corticosteroid therapy to treat on-target-off-tumour toxicities was lower than those in the pivotal ZUMA-1 cohorts. Similarly, Caimi and colleagues examined prophylactic tocilizumab administration 1 h before CD19-directed CAR T-cell infusion in 20 patients with relapsed or refractory non-Hodgkin lymphoma.…”

“…Whether early or preemptive corticosteroids and immunomodulators should continue to be used to mitigate CAR T-cell therapy-related toxic effects, when such a strategy is associated with an increased risk of infections and diminished SARS-CoV-2 vaccine responses, remains a timely question and probably will involve a balancing act. 1 To that end, Topp and colleagues 2 and Caimi and colleagues 3 provided a set of results showing the potential of preemptive corticosteroids and tocilizumab, respectively, to mitigate the risks of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). 2 , 3…”

“… 1 To that end, Topp and colleagues 2 and Caimi and colleagues 3 provided a set of results showing the potential of preemptive corticosteroids and tocilizumab, respectively, to mitigate the risks of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). 2 , 3…”