Clinical and Economic Burden of Tumor Lysis Syndrome Among Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Introduction: Tumor lysis syndrome (TLS) can be a life-threatening complication in patients with hematologic malignancies. In chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), treatment guidelines identify a high risk of TLS for regimens containing anti-CD20-based chemoimmunotherapy (CIT), lenalidomide, obinutuzumab, or venetoclax. Patients who develop TLS require intensive care, adding to the overall clinical and economic burden of CLL/SLL. This study aimed to evaluate the clinical and economic burden of treatment-emergent TLS among patients with CLL/SLL treated with regimens with high risk of TLS.

Methods: The IBM MarketScan Research Databases (01/01/2006-04/30/2020) were used to identify adults with CLL/SLL who initiated a CIT-, lenalidomide-, obinutuzumab-, or venetoclax-based regimen on or after 01/01/2007 or upon treatment approval date if post-2007 (index date) and had ≥12 months and ≥30 days of continuous eligibility pre- and post-index date, respectively. Treatment-emergent TLS was defined as developing TLS in the first 90 days of active treatment (based on claims with a TLS diagnosis or laboratory test results). The post-index period was divided into 30-day intervals until the end of the index regimen (earliest of start of next regimen or end of eligibility). Intervals pre-TLS were non-TLS intervals and all intervals starting from the TLS diagnosis were TLS intervals. If TLS occurred after the first 90 days of active treatment (non-treatment-emergent TLS), all intervals were non-TLS intervals and the post-index period was censored at TLS diagnosis. Per-patient-per-month (PPPM) healthcare resource utilization (HRU) and payer paid costs during TLS and non-TLS intervals were compared using rate ratios (RRs) and mean monthly cost differences (MMCDs), respectively, obtained from generalized linear models adjusted for baseline and time-varying confounders. The proportion of patients switching to a next therapy in the first 90 days post-index was compared between patients developing versus not developing TLS using Kaplan-Meier rates with log-rank P-value.

Results: Among 6,343 patients with CLL/SLL, 71 (1.1%, mean age: 66.4 years, 26.8% females; 22 treated with venetoclax; mean [median] duration of the entire index regimen: 16.0 [10.0] months) developed TLS during the first 90 days of active treatment and 6,272 (98.9%, mean age: 65.9 years, 34.1% female; 170 treated with venetoclax; mean [median] duration of the entire index regimen: 22.0 [14.5] months) did not. Among all 6,343 patients, there were 1,129 TLS intervals and 138,429 non-TLS intervals observed post-index. All patients incurred considerable cumulative costs over the entire index regimen duration (TLS cohort: $201,200; non-TLS cohort: $158,590). Developing TLS was associated with 1.7 times more inpatient (IP) admissions (P<0.001; Fig. 1a), 2.0 times more days of IP stay (P=0.012), 22% fewer days of antineoplastic drug administration (P=0.020; Fig. 1a), and $3,062 PPPM higher healthcare costs (P=0.016), driven by significantly higher IP costs PPPM (MMCD=$1,688; P=0.044; Fig. 1b) vs. not developing TLS. Higher costs during TLS intervals were observed for patients initiated on a venetoclax-based regimen (TLS intervals: $24,170 PPPM; non-TLS intervals: $20,091 PPPM) and patients initiated on a non-venetoclax-based regimen (TLS intervals: $8,746 PPPM; non-TLS intervals: $6,915 PPPM). In the first 90 days post-index, HRU and costs were higher than when averaged over the entire duration of the index regimen, regardless of developing TLS or not (Table 1). Among patients not developing TLS, those treated with a venetoclax-based regimen had numerically higher cumulative TLS prevention costs during the first 90 days post-index ($4,398) than those treated with a non-venetoclax-based regimen ($2,879). Patients developing TLS switched more quickly to a next line of therapy in the first 90 days of treatment compared to those not developing TLS (12.6% vs. 5.1%, P=0.006; Table 2).

Conclusions: In this study of CLL/SLL patients treated with CIT-, lenalidomide-, obinutuzumab-, or venetoclax-based regimens, TLS led to a significant HRU and cost burden (mostly driven by IP admissions) and a higher rate of treatment switching. Consideration of available treatment options based on patient goals and treatment expectations is warranted before selecting a treatment with a high risk of developing TLS.

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