(UroToday.com) The 2022 Annual Meeting of the American Urological Association was host to a podium presentation by Dr. Kyle Rose from Moffitt Cancer Center who presented real-world data on the antegrade administration of reverse thermal mitomycin (JEMLYTO®) for primary chemoablation of upper tract urothelial carcinoma (UTUC) via a percutaneous nephrostomy tube.
Based on results from the pivotal OLYMPUS trial, JELMYTO® is currently approved for low-grade UTUC. Patients in that trial were primarily treated via the retrograde approach with ureteral catheters at time of endoscopy. Following induction therapy, 59% of patients had a complete response. To potentially minimize the adverse effects of 44% ureteral stenosis (low or high grade) seen with patients in this trial, the requirement for general anesthesia with endoscopic instrumentation, and cost/medical resource utilization in the operating room, Dr. Rose and colleagues hypothesized that administration of this medicine via a percutaneous nephrostomy tube (PCNT) may minimize these complications. Thus, the objective was to report the safety profile and effectiveness of antegrade administration of JELMYTO® via a PCNT for UTUC.
This analysis pooled data from four tertiary referral centers. For the safety analysis, it required that patients have received at least one dose through the PCNT. Dr. Rose used NCI’s Common Terminology Criteria for Adverse Events, v5.0. Ureteral stenosis was defined as discrete narrowing of the ureter on direct vision ureteroscopy or pyelogram that required dilation or stenting for ureteroscope passage. They also conducted an efficacy analysis (CR rate, duration of response) that required patients to receive at least 5/6 induction doses.
PCNTs were placed by interventional radiology and at that time a nephrostogram was performed to measure the renal pelvis dimensions. 4 mg/mL mitomycin was injected, with a maximum volume of 15 mL. Induction therapy was performed once weekly for 6 weeks. For primary disease evaluation, a ureteroscopy was performed after the completion of induction therapy.
32 patients received at least one dose of JEMLYTO® through a PCNT between June 2020 and November 2021. The median age was 74.5 years, 91% were Caucasian, 69% were male and 22% had solitary kidneys. Four (14%) patients had a simultaneous ipsilateral ureteral tumor.
With regards to safety analysis:
- 3 patients did not receive at least 5 of 6 induction courses
- Discontinuation for:
- UTI: 1
- Herpes Zoster Infection: 1
- Dislodgement of PCNT into peripelvic cyst
- Discontinuation for:
- 30 total adverse events occurred in 14 patients (44%): non grade 4-5
- No deaths occurred
- 5 (16%) readmissions
- 4 (12.5%) emergency department visits
Ureteral stenosis occurred in only 3 (9%) of patients. Although the definition of stenosis in this study was different than that used in the OLYMPUS trial,1 these results are significantly better than the 44% rate reported in the trial. Of these 3 patients:
- 2 underwent balloon dilation
- One required transient stent placement for passive dilation (1 week)
- No patients had evidence of recurrence at a median of 10.0 months
There was no evidence of percutaneous nephrostomy tract seeding in any patients. There was no deterioration of renal function based on eGFR.
With regards to efficacy analysis:
- CR in 59% of patients (Equivalent to OLYMPUS)
- No recurrence with median follow up of 9.0 months (5.0-11.0)
- PR in 38% of patients
- No response in 3%--> pathologic upgrading to high grade disease radical nephroureterectomy
A subanalysis of 13 patients with residual tumor present at induction therapy initiation demonstrated:
- CR: 5 (38%)
- PR: 7 (54%)
- No response: 1 (8%)
Off label use of JELMYTO in patients with high grade UTUC demonstrated:
- PR: 2 patients
- CR: 1 patient
The authors concluded that mitomycin gel administered through an antegrade PCNT for UTUC offers a favorable side effect profile with a low rate of ureteral stenosis with no requirement for general anesthesia or utilization of operating room resources. Limitations of this study included its retrospective nature, small sample size, the reliance on patient-reported outcomes/complications, and the variability of multisite practice patterns.
Presented by: Kyle Rose, MD, SUO Clinical Fellow, Moffitt Cancer Center, Tampa, FL
Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.
- Kleinmann N, Matin SF, Pierorazio P, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial. Lancet Oncol. 2020;21(6):776-785. N, Matin SF, Pierorazio P, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial. Lancet Oncol. 2020;21(6):776-785.
Real-World Experience on the Safety Efficacy of Antegrade Administration of JELMYTO® for UTUC via Percutaneous Nephrostomy Tube - Kyle Rose