848P - Mortality after rasburicase vs allopurinol anti-hyperuricemia monotherapy in patients with liquid tumors

Background

This observational real-world study used propensity score matching (PSM) to compare tumor lysis syndrome (TLS) associated mortality in patients (pts) with hematological malignancies who received either rasburicase or allopurinol monotherapy. Goldman/Cairo previously published that rasburicase significantly, more rapidly reduces uric acid exposure (AUC) compared to allopurinol in pts with/at risk of TLS.

Methods

In 2021, 266 oncologists provided anonymized data for 715 liquid tumor pts treated in past year for hyperuricemia (HU) risk and TLS potential. Out of 715, 282 rasburicase and allopurinol pts without spontaneous TLS or TLS before HU treatment (Tx) were matched using 11 pre-HU Tx covariates: acute renal failure, age, anti-cancer Tx, creatinine, gender, LDH, perceived risk, renal disease, tumor type, uric acid, and white blood cells. Matched pts met 1:1, nearest neighbor, caliper matching requirements (width=0.2) of standard deviation of logit of the PSM (d score) on covariates, regardless of whether pts later developed TLS post-HU Tx. Assessments include mean uric acid (UA) levels, anti-cancer Tx, and, as feasible, timing of death relative to HU Tx.

Results

The PSM was almost 0.6 before and near 0 after matching; no covariate had a large imbalance (│d│>0.25) before and after. Of 141 pts in each pt group, TLS-associated mortality was significantly less likely among rasburicase pts (2.1% [n = 3] vs. 7.1% [n = 10], P = 0.047) (71% reduction). Of 63 pt subset who developed TLS after HU Tx, TLS-associated fatalities were even less likely among rasburicase vs. allopurinol pts (8.3% [n = 3] vs. 37% [n = 10], P = 0.005). Comparing 13 who died vs. 269 who lived, no significant difference in mean UA was found (13.5 mg/dL vs. 11.4, respectively). Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (R-CHOP) was the predominant Tx among those who did not die (15%, n = 41). Only 1/13 pts died of R-CHOP. Seven pts died within 2 weeks of allopurinol (n = 6) or rasburicase (n = 1) monotherapy (timing not established for other 6).

Conclusions

PSM corrects before and after overall covariate and individual baseline covariate imbalances and rasburicase compared with allopurinol significantly reducing TLS-associated mortality.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Sanofi.

Disclosure

J.R. Gallagher, S. Carroll: Financial Interests, Full or part-time Employment: Clarity Pharma. E.J. Drea, Y.J. Barnes, C. Clark: Financial Interests, Stocks/Shares: Sanofi. All other authors have declared no conflicts of interest.