Clinical and economic burden of tumor lysis syndrome among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: A real-world US retrospective study

Journal of Managed Care & Specialty Pharmacy, 2022


Tumor lysis syndrome (TLS) is a potentially fatal complication of antineoplastic treatments for hematologic malignancies, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients developing TLS require intensive care, adding to the overall clinical and economic burden of CLL/SLL.


To analyze TLS-associated health care resource utilization (HCRU) and costs in patients with CLL/SLL treated with regimens associated with a high TLS risk (per treatment guidelines), ie, anti-CD20-based chemoimmunotherapy (CIT), lenalidomide, obinutuzumab, or venetoclax.


Adult patients with CLL/SLL in the MarketScan Databases (January 1, 2006, to April 30, 2020) initiated on CIT, lenalidomide, obinutuzumab, or venetoclax (index date) on or after January 1, 2007, were included in the analysis. Treatment-emergent TLS was defined as TLS occurring in the first 90 days of active treatment. The post-index period was divided into 30-day intervals until the end of the index regimen; intervals pre-TLS were non-TLS intervals and those starting from the TLS event were TLS intervals. Per-patient-per-month (PPPM) HCRU and costs were compared between TLS and non-TLS intervals using generalized linear models adjusted for baseline and time-varying confounders. The proportion of patients in the TLS cohort (patients with treatment-emergent TLS) and non-TLS cohort (patients with no treatment-emergent TLS) who switched treatment within 90 days post-index was compared using Kaplan-Meier rates with logrank P values.


Among 6,343 patients with CLL/SLL, 71 (1.1%) developed treatment-emergent TLS (venetoclax: 11.5%; other regimens: 0.8%) after a mean (median) of 12.7 (7.0) days following treatment initiation (mean [median] duration of index regimen: 16.0 [10.0] months); 12 (0.2%) developed clinical TLS (venetoclax: 3.1%; other regimens: 0.1%). TLS was associated with 1.7 times more inpatient admissions (P < 0.001), 2 times more days of inpatient stay (P = 0.012), 22% fewer days of antineoplastic drug administration (P = 0.020), and $3,062 PPPM higher health care costs (P = 0.016), which were mainly driven by $1,688 PPPM higher inpatient costs (P = 0.044). Higher costs were observed among both patients who initiated venetoclax (TLS: $24,170; non-TLS: $20,091) and those who initiated other regimens (TLS: $8,746; non-TLS: $6,915). More patients in the TLS vs non-TLS cohort switched treatment in the first 90 days of treatment (12.6% vs 5.1%, P = 0.006).


TLS was associated with a substantial cost burden (driven by inpatient costs) and higher rate of treatment switching (vs non-TLS cohort) in patients with CLL/SLL treated with CIT, obinutuzumab, lenalidomide, or venetoclax. The risk of treatment-emergent TLS and associated incremental HCRU and costs, as well as the potential impact on quality of life, should be weighed when evaluating the risk-benefit of therapies in CLL/SLL management.

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Rogers KA, Lu X, Emond B, Côté-Sergent A, Kinkead F, Lafeuille MH, Lefebvre P, Huang Q