Treatment-emergent adverse events (TEAEs) of any grade at either dose level occurred in all patients; grade ≥3 occurred in 96% of patients. Some 74% of patients had cytokine release syndrome (CRS) of any grade, and 9% had grade-3 CRS. There were no cases of grade-4 or -5 CRS. More than one-third (39%) of patients had neurologic events, “but only 5 had grade-3 or -4 neurotoxicity and no grade-5 neurotoxicity,” she said. Three-fourths (75%) of patients received tocilizumab and/or steroids to manage CRS and neurologic events. Early intervention with tocilizumab and steroids was instituted to manage toxicities. “These particular CAR T-cell–related side effects were fairly similar in the double-refractory subgroup of patients,” she said.
The most common grade 3/4 TEAEs were anemia (78%), thrombocytopenia (70%), neutropenia (56.5%), and leukopenia (43.5%). Grade ≥3 tumor lysis syndrome occurred in 17.4% of patients. DLTs occurred in 2 patients at dose level 2; both were resolved.
Two patients in the high-dose arm had DLTs; 1 had grade 4 hypertension and 1 patient had grade 3 encephalopathy, grade 3 muscle weakness, and grade 4 tumor lysis syndrome.
Patients with higher tumor burden as measured by the sum of product diameters (SPD) of target lymph nodes appeared to be more likely to develop neurotoxicity. All 9 patients with any grade of neurologic event had SPD values >15. High early phase interleukin (IL)-16 and tumor necrosis factor (TNF) levels were also significantly associated with the development of neurologic events. IL-16 and TNF levels directly correlated with lymph node tumor burden.
The findings justify the phase II portion of the study, which is enrolling patients at dose level 2, said Siddiqi.
Siddiqi T, Soumerai JD, Dorritie KA, et al. Rapid undetectable MRD (uMRD) responses in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T cell product: updated results from Transcend CLL 004, a phase 1/2 study including patients with high-risk disease previously treated with ibrutinib. Presented at: 2019 ASH Annual Meeting; December 7-10, 2019; Orlando, FL. Abstract 503.
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