Description
Mitomycin is an alkylating drug isolated from the broth of Streptomyces caespitosus. A cytotoxic drug, mitomycin inhibits the synthesis of deoxyribonucleic acid (DNA) and at high concentrations, cellular RNA and protein synthesis are also suppressed. In a gel preparation strictly for pyelocalyceal solution, the solution consists of mitomycin 40 mg and mannitol 80 mg in each single-dose vial. 

The mitomycin gel-form must be reconstituted in sterile hydrogel and administered by instillation into the pyelocalyceal system via ureteral catheter or nephrostomy tube. There it forms a semisolid gel which dissolves from normal kidney urine flow, releasing mitomycin for up to 4 to 6 hours.

While primarily metabolized in the liver, metabolism occurs in other tissues as well. The rate of clearance is likely inversely proportional to the maximal serum concentration due to saturation of the degradative pathways.

Policy
Mitomycin Gel is considered medically appropriate if ALL of the following criteria are met and The prescriber is a specialist in the area of the patient’s diagnosis (e.g., oncologist, urologist) or has consulted with a specialist in the area of the patient’s diagnosis.

I.Jelmyto (mitomycin for pyelocalyceal solution) is considered MEDICALLY NECESSARY for the FDA-approved treatment of adults with low-grade upper tract urothelial cancer (LG-UTUC) who meet ALL of the following criteria:

• Member is least 18 years of age
• Member has histologically confirmed, non-invasive, low-grade upper tract urothelial carcinoma (LG-UTUC) in the pyelocalyceal system, with no evidence of high-grade, muscle-invasive, locally advanced, or metastatic disease.
• Member does not have untreated concurrent urothelial cancer (UC) outside the target area (unless already treated)
• Member has at least one measurable papillary tumor 5 to ≤ 15 mm
• Member does not have a perforation of the bladder or upper urinary tract

II. When Jelmyto (mitomycin for pyelocalyceal solution) is considered MEDICALLY NECESSARY, initial therapy will be authorized for a period of 6 weeks based on the FDA dosing recommendations:

• Jelmyto is for pyelocalyceal use only and not for intravenous use, topical use, or oral administration.
• Jelmyto will be given via pyelocalyceal route once weekly for six weeks (6 doses total).
• The dose of Jelmyto to be instilled is 4 mg per mL via ureteral catheter or nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography, not to exceed 15 mL (60 mg of mitomycin).

INFORMATIONAL NOTE: As stated in package insert, member will receive 1.3 g of sodium bicarbonate orally the evening prior to, the morning of, and 30 minutes prior to instillation procedure (total of 3.9 g).

General anesthesia, local anesthesia, sedation, prophylactic antibiotics and/or antihistamines may be used at the discretion of the treating urologist. If the patient is to be anesthetized, advise the patient not to take sodium bicarbonate within 30 minutes prior to the treatment. Consider withholding diuretics one day prior to instillation until 4 hours post-instillation.)

III. Continued therapy will be authorized for 11 months (11 once a month instillations) when the following criteria are met:

• Only if member has had a complete response 3 months after Jelmyto initiation (initial 6 weekly doses), then Jelmyto may be administered once a month for a maximum of 11 additional instillations.
• The total number of instillations the patient does not exceed 17 instillations of Jelmyto (6 initial weekly doses, 11 maintenance monthly doses)
• There is absence of unacceptable toxicity from the drug (e.g., severe ureteric obstruction, bone marrow suppression, etc.)

INFORMATIONAL NOTE: As per the clinical trials, only those patients that showed a complete response to Jelmyto 3 months after initial initiation went onto the maintenance phase. Those in the maintenance phase were allowed to receive up to 11 additional instillations at once a month dosing.)

IV. Jelmyto (mitomycin for pyelocalyceal solution) is considered MEDICALLY NECESSARY for the following off-label uses:

• Bladder Cancer — Upper GU Tract Tumors
  • Primary treatment for a non-metastatic, residual, low-grade, low volume (5 – 15 mm), solitary tumor in the upper urinary tract for a patient who is not a candidate for or not seeking nephroureterectomy as a definitive treatment
    • Complete or near complete endoscopic resection or ablation is recommended prior to mitomycin ureteral gel application
    • Mitomycin for pyelocalyceal application may be administered via ureteral catheter or a nephrostomy tube

V. Jelmyto (mitomycin for pyelocalyceal solution) is investigational/unproven therefore considered NOT MEDICALLY NECESSARY for all other uses.

Uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be MEDICALLY NECESSARY if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and NOT MEDICALLY NECESSARY.

References 

1. Jelmyto (mitomycin). (Prescribing Information) UroGen Pharma, Inc. Princeton, NJ. April 2020. 
2. FDA Approves First Therapy for Treatment of Low-Grade Upper Tract Urothelial Cancer. FDA News Release. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-treatment-low-grade-upper-tract-urothelial-cancer. April 15, 2020. 
3. National Comprehensive Cancer Network. Bladder Cancer (Version 4.2020). https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed May 4, 2020. 
4. Jelmyto. National Comprehensive Cancer Network: Drugs and Biologics Compendium. [Available at http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=367 (accessed 5/4/2020) 
5. Roupret M, Babjuk M, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2017 Update. Eur Urol. 2018:73(1):111-122.
6. MICROMEDEX Healthcare Series. Drugdex Evaluations. (2020, April). Mitomycin. Retrieved April 29, 2020 from MICROMEDEX Healthcare Series.
7. National Comprehensive Cancer Network. (2020). NCCN Drugs & Biologics Compendium^®. Mitomycin; solution, pyelocalyceal. Retrieved April 29, 2020 from the National Comprehensive Cancer Network.
8. U. S. Food and Drug Administration. (2020, April). Center for Drug Evaluation and Research. JELMYTO™ (mitomycin) for pyelocalyceal solution. Retrieved April 29, 2020 from:
9. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211728s000lbl.pdf.

Coding Secrtion 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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