ABSTRACT
BACKGROUND: Cytokine release syndrome (CRS) is a common adverse event of CAR T cell or bispecific antibody (bsAb) therapy. Anti-IL6/IL6R drugs are used in the management of auto-immune diseases. Some reports showed increased risk of bacterial infection in this context. In onco-hematology, there are few data about the occurrence of infection after administration of an anti-IL6/IL6R for CRS. METHODS: We retrospectively reviewed all consecutive patients treated in Gustave Roussy Cancer Campus between 2018 and 2021, who received anti-IL6/IL6R for CRS due to bsAb in phase I clinical trials or adoptive cellular therapy (ACT). We constituted a control group including all the patients treated in the same clinical trials or standard of care ACT, naïve of anti-IL6/IL6R. RESULTS: Fifty-two patients have been included. In the anti-IL6/IL6R group (n = 26), five patients developed a grade 2 to 5 infection within a month after anti-IL6/IL6R treatment, including two grade 5 infections. In the control group (n = 26), only one patient had a grade 3 infection. The two patients who had grade 5 infections were treated for diffuse large B cell lymphoma (DLBCL), one with bsAb and the other with CAR T cell. Fifty percent (3/6) of DLBCL patients who received an anti-IL6/IL6R presented an infection, one of which was a grade 5. In solid tumor patients treated with bsAb and anti-IL6/IL6R, only one patient (/9, 11%) developed a grade 2 viral infection. CONCLUSION: It seems that the use of anti-IL6/IL6R in CRS secondary to bsAb administration in solid tumors patients does not significantly increase the risk of infection, as opposed to DLBCL patients where secondary infection might be a concern.
Subject(s)
Antibodies, Bispecific , Lymphoma, Large B-Cell, Diffuse , Humans , Cytokine Release Syndrome/chemically induced , Retrospective Studies , Lymphoma, Large B-Cell, Diffuse/drug therapyABSTRACT
Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.
