Table 1.

Summary of the clinical interventions with kinase inhibitors for the mitigation or prevention of CRS induced by T cell engaging therapies

Study	Therapy	Disease	Results/comments
Gauthier et al., 2020 NCT01865617	CD19 CAR-T cells (CD28 and 4–1BB) + ibrutinib	CLL	Ibrutinib reduced CRS severity while retaining efficacy. Con-ibrutinib cohort: 14/19 patients experienced CRS, among which 0/19 were grade ≥3 CRS No-ibrutinib cohort: 18/19 patients experienced CRS, among which 2/19 were grade ≥3 CRS.
Uy et al., 2019 NCT02152956	flotetuzumab + ruxolitinib	AML	Prophylaxis ruxolitinib modified the cytokine profile but did not resolve CRS symptoms induced by flotetuzumab. Con-ruxolitinib cohort: 9/10 patients experienced CRS, among which 4/10 were grade 1 CRS, 5/10 were grade 2 CRS and 0/10 were grade ≥3 CRS. No-ruxolitinib cohort: 23/23 patients experienced CRS, among which 17/23 were grade 1 CRS, 5/23 were grade 2 CRS and 1/23 were grade ≥3 CRS.
Wei et al., 2020 Chi CTR1900025419	CD22/CD19 CAR-T cells + ruxolitinib	Ph+ ALL	Ruxolitinib was used to treat glucocorticoid-refractory CRS. After dexamethasone treatment, ruxolitinib resolved CRS symptoms. This was associated with a reduction of cytokines, ferritin and CRP levels and no apparent effect on the CAR-T cell anti-leukemic activity.
Zi et al., 2021 NCT04303520	CD22/ CD19 CAR-T cells + ruxolitinib	Ph+ ALL	Ruxolitinib was used to treat glucocorticoid and tocilizumab-refractory CRS. After tocilizumab and methylprednisolone treatment, ruxolitinib resolved CRS symptoms. This was associated with a reduction of cytokines, ferritin and CRP levels and no apparent effect on the CAR-T cell anti-leukemic activity.
ChiCTR190002531 (patient 1) ISRCTN19144142 (Patient 2).	CD7 CAR-T cells + ruxolitinib and etanercept	T ALL	Concomitant use of ruxolitinib and etanercept induced a change in cytokine profile but did not fully resolve CRS symptoms (administration of noradrenaline was sustained to mitigate CRS grade 3 in both patients)
Park et al., 2021 NCT04071366	CD19 CAR-T cells + itacitinib (JAK1 inhibitor)	r/r B cell malignancies	Ongoing study
Assi et al., 2017 77	Ponatinib, bosutinib or dasatinib + blinatumomab	ALL	Two cases of grade 2 CRS (resolved with glucocorticoids and tocilizumab). One case was observed with dasatinib and the other with ponatinib.
King et al., 2019 78	Ponatinib, imatinib, nilotinib or dasatinib + blinatumomab	ALL	Blinatumomab was used to eliminate remaining ALL cells in patients with MRD and spare toxicity associated to chemotherapy. CRS (grade 1–2) was observed in 3/11 patients
Foà et al., 2020 NCT0244768	Dasatinib + blinatumomab	Ph+ALL	Concomitant use of blinatumomab and dasatinib was safe and efficacious.