Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma

Abstract

Background aimsB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.MethodsPatients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.ResultsEighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3–4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5–8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3–10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.ConclusionTLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.

The First Case of Multiple Myeloma Treated With ASCT followed by Anti-BCMA CART Cells using Retroviral Vector

“…In this case, we also observed the development of grade 3 CRS, but fortunately, the patient improved with treatment at 15 days, and ICANS has not been observed to date. After infusion of anti-BCMA CART cells, the peak expression of IL6 in patients was also much lower than reported in existing literature [16,17] . Thus, it appeared that autologous CART infusion after ASCT may reduce the degree of adverse effects in patients.…”

Precision Targeting and Genetically Modified T Cells for Targeting Cancer Cells

“…While CAR T cell therapy is an innovative method for treating cancer, it is not devoid of difficulties, as seen by a comprehensive list of negative side effects that often occur. The present research indicates that there are many harmful effects, such as allergies, B cell aplasia, cytokine release syndrome (CRS), neurological toxicity, and tumor lysis syndrome 52 . The key issue is on the proliferation of CAR T cells, which delicately controls the production of cytokines within the body's natural environment.…”

Toxicities, intensive care management, and outcome of chimeric antigen receptor T cells in adults: an update

“…TLS has been reported in 5–17% of CAR-T recipients [ 26 ] and is characterized by hypocalcaemia, hyperkalaemia, metabolic acidosis, hyperphosphatemia, hyperuricemia, and renal failure. TLS should be prevented and managed with adequate monitoring and standard care, including control of potassium and phosphorus intake during the risk period, hyperhydration, and reducing the level of uric acid (with allopurinol or rasburicase).…”