ROACTEMRA (tocilizumab)

Key points

Favourable opinion for reimbursement in the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and paediatric patients 2 years of age and older.

What therapeutic improvement?

No clinical added value in the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and paediatric patients 2 years of age and older.

Role in the care pathway?

Patients treated with chimeric antigen receptor (CAR) T cells are prone to numerous adverse events, including potentially life-threatening cytokine release syndrome (CRS). To date, two CAR T cell-based medicinal products have been granted a marketing authorisation: YESCARTA (axicabtagene ciloleucel) and KYMRIAH (tisagenlecleucel) in the third and later-line treatment of DLBCL and KYMRIAH (tisagenlecleucel) in B-cell ALL up to the age of 25 years. In clinical studies involving CAR T cells, several treatment algorithms have been developed to manage this CAR T cell-induced syndrome, with differences in terms of severity grading criteria (lack of consensual definition). Depending on the algorithm (see Annexes), the use of tocilizumab, either alone or combined with corticosteroids, may be recommended for CRS considered to be moderate.

Depending on the severity of the cytokine release syndrome, management is limited to the use of symptomatic treatments or may require a stay in intensive care in the event of severe or life-threatening syndrome. Corticosteroids may be administered.

Role of ROACTEMRA (tocilizumab) in the care pathway:

ROACTEMRA (tocilizumab) remains a first-line treatment for severe or life-threatening cytokine release syndrome (CRS) induced by chimeric antigen receptor (CAR) T cell treatments with an MA in adults and paediatric patients 2 years of age and older.

The optimum administration regimen (dosage, number of doses, optimum time), along with the role of corticosteroids, remain to be defined. Extensive use of tocilizumab in low-grade CRS or in preventive situations has been observed in the French DESCAR-T registry. However, the Committee highlights the fact that these situations are not covered by the MA for tocilizumab.

As stipulated in the SPCs for YESCARTA (axicabtagene ciloleucel) and KYMRIAH (tisagenlecleucel), its availability (at least four doses) should be ensured before infusion of CAR T cells.

It should be noted that the indication for ROACTEMRA (tocilizumab) is only validated from 2 years of age, whereas KYMRIAH (tisagenlecleucel) can be administered in children with no age restriction (in accordance with its MA).

Special recommendations

The Committee calls for the participation of all qualified centres in the DESCAR-T registry in order to obtain exhaustive, high-quality observational data for future assessments concerning CAR-T cell-based medicinal products.