Characterization of toxicities associated with sulfamethoxazole/trimethoprim (TMP-SMX) for pneumocystis jirovecii prophylaxis in patients with glioblastoma (GBM).

Abstract

e14066 Background: Standard of care treatment for GBM includes temozolomide (TMZ) chemotherapy, which induces significant lymphopenia and reduction in CD4 counts. In the initial phase 2 trial of TMZ for GBM, 2 out of the first 15 patients developed pneumocystis pneumonia (PCP), and PCP prophylaxis became routine practice in patients receiving TMZ. However, a previous study demonstrated a number needed to treat of 288 to prevent one case of PCP in patients with GBM receiving TMZ. In addition, TMP-SMX, the most used prophylaxis, carries its own risks and adverse effects. This study aimed to identify the incidence of adverse events with TMP-SMX prophylaxis in a large cohort of GBM patients treated with TMZ. Methods: We conducted a retrospective, single-center, observational cohort study at the University of Pennsylvania. Patients included were 18 years or older, had a diagnosis of GBM, were treated with concomitant and/or adjuvant TMZ as part of first-line therapy between July, 2019, and July, 2024, and received TMP-SMX for PCP prophylaxis. Toxicities were graded using the Common Terminology Criteria for Adverse Events version 5.0. For toxicities based on serum values, patients without baseline serum values prior to treatment were excluded. The primary outcome was the incidence of dermatologic toxicity with secondary outcomes including the incidence of creatinine elevation, hyperkalemia, and liver injury defined by elevations in total bilirubin or transaminases. Results: Of the 354 patients who met the inclusion criteria, the mean age was 62.5 years and 59.9% were male. On average, patients completed 4 cycles of adjuvant TMZ. 17.2% of patients experienced a rash. The frequencies of additional key toxicities and the percent of toxicities that occurred during the concomitant phase are listed in the table. Creatinine and alanine aminotransferase (ALT) elevations were the most common adverse events. Grade 3 and 4 toxicities were infrequent with incidence of 3.0% for ALT, 1.1% for aspartate aminotransferase (AST), 0.75% for bilirubin, and 0.29% for creatinine elevations. 20.6% of patients discontinued TMP-SMX but only 23.3% resumed prophylaxis with an alternative agent. Conclusions: We demonstrate that hepatic, renal, and dermatologic toxicities associated with TMP-SMX prophylaxis among patients receiving TMZ for GBM are common although not usually severe. Although we cannot be certain that all toxicities were attributable to TMP-SMX, these data underscore the potential harms of PCP prophylaxis with TMP-SMX in patients with GBM receiving TMZ and challenge the paradigm of routine prophylaxis. Toxicity Any phase N, (%) Concomitant phase, % Creatinine elevation (grade ≥ 2 only) 112 (32.8) 49.1 ALT elevation 83 (31.2) 83.1 AST elevation 65 (24.4) 73.8 Hyperkalemia 74 (21.1) 70.3 Rash 61 (17.2) 63.9 Hyperbilirubinemia 32 (12.0) 59.4