Introduction
Jelmyto (mitomycin gel) is a sterile, pyridine-free, preservative-free, mitomycin-containing gel approved by the FDA in April 2020. It represents a novel approach to treating low-grade upper tract urothelial cancer (LG-UTUC) through localized administration via ureteral catheter. Jelmyto offers a minimally invasive alternative to surgical intervention for selected patients with this challenging-to-treat condition.
Mechanism of Action
Jelmyto contains mitomycin, an alkylating agent that exerts its antineoplastic effects through covalent binding to DNA. The drug molecule cross-links complementary DNA strands, primarily at the N6 position of adenine and the O6 and N7 positions of guanine. This cross-linking inhibits DNA synthesis and transcription, ultimately leading to cell cycle arrest and apoptosis of rapidly dividing cancer cells. The hydrogel formulation allows for sustained local delivery directly to the tumor site while minimizing systemic exposure.
Indications
Jelmyto is indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). This includes tumors located in the renal pelvis and ureter. The approval was based on the OLYMPUS trial, which demonstrated complete response rates in patients with this specific malignancy.
Dosage and Administration
Standard dosing: Jelmyto is administered at a concentration of 4 mg/mL. The recommended dose is 1 mL instilled once per week for 6 weeks. If a complete response is not achieved after 6 doses, an additional 6 weekly instillations may be administered. Administration: The gel is administered via ureteral catheter or nephrostomy tube by a qualified healthcare professional. The product must be administered at room temperature (20-25°C/68-77°F). Patients should be positioned to maximize contact time with the tumor site and remain in this position for at least 1 hour following instillation. Special populations:- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: No specific recommendations available
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Systemic absorption is minimal due to localized administration. In clinical studies, plasma concentrations of mitomycin were generally below the limit of quantification (0.1 ng/mL). Distribution: The hydrogel formulation is designed for localized delivery with minimal systemic distribution. Metabolism: Mitomycin undergoes reductive metabolism primarily in the liver, but also in other tissues including kidneys. The metabolism is mediated by NADPH-cytochrome P450 reductase and DT-diaphorase. Elimination: The elimination half-life of systemically absorbed mitomycin is approximately 50 minutes. Primary elimination occurs through hepatic metabolism and renal excretion.Contraindications
- Hypersensitivity to mitomycin or any component of the formulation
- Presence of perforation or compromised integrity of the urinary tract mucosa
- Concurrent urinary tract infection
Warnings and Precautions
Ureteric obstruction: May cause ureteric obstruction requiring temporary ureteral stent placement. Monitor for flank pain and decreased urine output. Embryo-fetal toxicity: Can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiation. Myelosuppression: Although systemic exposure is minimal, monitor for bone marrow suppression, particularly in patients with compromised bone marrow function. Secondary malignancies: Alkylating drugs including mitomycin increase the risk of secondary malignancies. Impaired wound healing: May interfere with normal wound healing processes.Drug Interactions
Formal drug interaction studies have not been conducted. However, based on mitomycin's properties:
- Live vaccines: Avoid concurrent administration
- Other myelosuppressive agents: May enhance bone marrow toxicity
- Drugs affecting hepatic enzymes: Potential for altered metabolism
Adverse Effects
Most common adverse reactions (≥20%):- ureteral obstruction (58%)
- flank pain (56%)
- hematuria (44%)
- urinary tract infection (42%)
- renal dysfunction (36%)
- fatigue (33%)
- nausea (31%)
- abdominal pain (27%)
- vomiting (25%)
- dysuria (22%)
- Ureteral obstruction requiring stent placement
- Sepsis
- Pyelonephritis
- Renal failure
Monitoring Parameters
- Complete blood counts (baseline and periodically during treatment)
- Renal function (serum creatinine, BUN)
- Urinalysis and urine culture
- Signs and symptoms of ureteral obstruction
- Urinary tract infection symptoms
- Pregnancy testing in females of reproductive potential
- Response assessment via ureteroscopy at 3-month intervals
Patient Education
- Report any signs of infection (fever, chills, burning during urination) immediately
- Be aware of potential side effects including flank pain, blood in urine, and urinary symptoms
- Use effective contraception during treatment and for 6 months after final dose
- Inform all healthcare providers about Jelmyto treatment
- Understand the need for regular follow-up and monitoring appointments
- Report any new or worsening symptoms promptly
References
1. FDA Approval: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-gel-low-grade-upper-tract-urothelial-cancer 2. Kleinmann N, et al. Phase 3 OLYMPUS Study: A Novel Oncology Drug Delivery System. J Urol. 2020;203(4):571-580. 3. Jelmyto [package insert]. UroGen Pharma, Inc.; 2020. 4. Cutress ML, et al. Upper tract urothelial carcinoma: current treatment and outcomes. Urology. 2012;79(4):749-756. 5. Rouprêt M, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update. Eur Urol. 2021;79(1):62-74.