Evaluation of the management of PARP inhibitor toxicities in ovarian and endometrial cancer within a multi-institution health-system.

INTRODUCTION: Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have become a cornerstone of therapy in the management ovarian cancer and other cancers. PARPi are associated with significant toxicities and management strategies are primarily founded on clinical trial experience. This study aimed to provide an evaluation of patients receiving PARPi therapy within an academic health-system. METHODS: A retrospective, observational study of adult patients with gynecologic malignancy was conducted at the University of Pennsylvania Health System. Data was collected on patients prescribed a PARPi between December 2014 and October 2019. The primary endpoint was the status of PARPi therapy at the end of the study period. Key secondary endpoints included toxicity management strategies, time to discontinuation due to toxicity, progression free survival (PFS), and overall survival (OS). RESULTS: Of the 85 patients included, 45 (53%) received olaparib, 24 (28%) niraparib, and 16 (19%) rucaparib. Twenty-nine patients (34%) continued on therapy, 15 (18%) discontinued due to toxicity, and 41 (48%) discontinued due to progression. Fifty-one percent of patients required a dose reduction due to toxicities. The median time to discontinuation due to toxicity was 69 days (9-353). Median PFS was 181 days (9-365) and median OS was 338 days (9-365). CONCLUSION: PARPi therapy is associated with numerous toxicities that are best managed through a multi-modal approach. Importantly, about half the patients in the current study required a dose reduction. Overall, this observational study outlines the incidence of PARPi toxicities and reviews potential management strategies, further guiding practitioners in an area with limited real-world experience.

Pentosan polysulfate for the treatment of hemorrhagic cystitis after allogeneic hematopoietic cell transplant.

INTRODUCTION: Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. METHODS AND RESULTS: This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10). CONCLUSION: Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.

Day 4 vs. day 12 G-CSF administration following reduced intensity peripheral blood allogeneic stem cell transplant.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) hastens neutrophil engraftment and reduces infections after allogeneic hematopoietic cell transplant (alloHCT), yet the optimal start date is unknown. Additionally, concurrent G-CSF and methotrexate for graft-vs-host disease (GVHD) prophylaxis may potentiate myelosuppression, and prolonged G-CSF is costly. Our institution changed from day + 4 to day + 12 G-CSF initiation following reduced intensity (RIC) alloHCT with methotrexate GVHD prophylaxis. METHODS: We retrospectively compared day + 4 and day + 12 G-CSF initiation after RIC alloHCT from 2017-2021. The primary endpoint was the time to neutrophil engraftment. Secondary endpoints included length of stay (LOS) and the time to platelet engraftment as well as the incidence of infectious events, acute GVHD (aGVHD), and mucositis. RESULTS: Thirty-two patients were included in each group with similar baseline characteristics. We observed faster neutrophil engraftment (median 12 vs. 15 days, p = 0.01) and platelet engraftment (median 13 vs. 15 days, p = 0.026) with day + 4 vs. day + 12 G-CSF initiation. Median LOS was 23 days (range, 19-32) with day + 4 initiation vs. 24 days (21-30) with day + 12 (p = 0.046). The incidence of culture-negative febrile neutropenia (p = 0.12), any grade aGVHD (p = 0.58), and grade 2-4 mucositis (p = 0.8) were similar between groups. CONCLUSION: Compared to day + 4, day + 12 G-CSF initiation following RIC alloHCT had a longer time to neutrophil and platelet engraftment. Day + 12 initiation also resulted in longer LOS, which while statistically significant, was potentially of limited clinical significance. These findings are hypothesis generating.