Subject:
Mitomycin for Pyelocalyceal Solution (Jelmyto)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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While the majority of urothelial cancers occur in the bladder, upper tract urothelial cancer (UTUC) corresponds to a subset of urothelial cancers that arise in the lining of the kidney or the ureter (the long, thin tube that connects that kidney to the bladder). UTUC can block the ureter or kidney, causing swelling, infections and impairment of kidney function in some patients. UTUCs can develop as low-grade or high-grade tumors. In general, low-grade tumors are not invasive and very rarely spread from the kidney or ureter. However, they often recur and management involves treating visible tumors and trying to preserve the urinary tract, as these tumors are more likely to recur in the urinary system than they are to spread. UTUC is rare and accounts for 5-10% of all urothelial cancers. The peak incidence is in age 70 to 90 years of age. There are about 5000 cases every year in the United States.
On April 15, 2020, the U.S. Food and Drug Administration approved Jelmyto (mitomycin for pyelocalyceal solution), the first therapy to treat low-grade upper tract urothelial cancer (UTUC). The FDA approved Jelmyto is based on the results of a prospective, multicenter, phase 3, open-label, single-arm clinical trial involving 71 patients with low-grade UTUC (OLYMPUS - NCT02793128). These patients had never undergone treatment or had recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor (a tumor shaped like a small mushroom with its stem attached to the inner lining of an organ). Patients received Jelmyto once a week for six weeks and, if assessed as a complete response (complete disappearance of the papillary tumor), monthly for up to 11 additional months. Efficacy of Jelmyto was evaluated using urine cytology (a test to look for abnormal cells in a patient’s urine), ureteroscopy (an examination of the upper urinary tract) and biopsy (if warranted) three months following the initiation of therapy. The primary endpoint was complete response at three months following initiation of therapy. A complete response was found in 41 of the 71 patients (58%) following six treatments of Jelmyto administered weekly. Durability of the effect of Jelmyto in patients with a complete response was also evaluated using urine cytology, ureteroscopy and biopsy (if warranted) every three months for a year following the initiation of therapy. Nineteen patients (46%) who achieved a complete response continued to have a complete response at the 12-month mark.
Common side effects for patients taking Jelmyto were ureteric obstruction (narrowing or blockage of the ureter that may lead to excess fluid in the kidney due to a backup of urine), flank pain (pain occurring on the side of the body), urinary tract infection, hematuria (blood in the urine), renal dysfunction (inability of the kidney to function in its designed capacity), fatigue, nausea, abdominal pain, dysuria (painful or difficult urination) and vomiting. Jelmyto can cause serious side effects including ureteric obstruction, flank pain and urosepsis (bacteria in the bloodstream from a urinary tract infection). Patients with ureteric obstruction may require transient or long-term stents to relieve this obstruction. The obstruction may be persistent and did not resolve or did not resolve completely in 51% of patients who experienced obstruction due to Jelmyto. Jelmyto should be avoided in patients with a glomerular filtration rate (a test used to check how well the kidneys are working) of less than 30mL/min. Jelmyto is contraindicated in patients with perforation of the bladder or upper urinary tract.
[INFORMATIONAL NOTE: In the OLYMPUS study, ureteric obstruction was reported in 58% (n=41) of patients receiving Jelmyto, including 17% (n=12) of patients who experienced Grade 3 obstruction. The median time to first onset was 72 days (range: 15-462). Interventions in the 41 patients experiencing ureteric obstruction included ureteral stent placement (88%), balloon dilatation (32%), and nephroureterectomy (4.9%). In the 36 patients who required ureteral stent placement, the median duration of indwelling stents was 51 days (range: 1-292). Ureteric obstruction did not resolve or resolved with sequelae in 51% (n=21) of these patients. Of the 41 patients who experienced ureteric obstruction, 17% (n=7) experienced Grades 1-2 increase in serum creatinine. In the 42 patients who only received Jelmyto during the treatment phase (no maintenance therapy), ureteric obstruction was reported in 40% (n=17).]
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
I. 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.
II. Jelmyto (mitomycin for pyelocalyceal solution) is 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 low grade, non-invasive urothelial cancer (LG-UTUC) in the pyelocalyceal system
- 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 located above the ureteropelvic junction
- Member has not received Bacillus Calmette–Guerin (BCG) treatment for urothelial cancer in the last 6 months
- Member does not have a perforation of the bladder or upper urinary tract
III. 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.]
IV. 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 has does not exceed 17 instillations of Jelmyto (6 initial weekly doses, 11 maintenance monthly doses)
- There is absence of unacceptable toxicity from the drug (ex. 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.]
V. 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
VI. Jelmyto (mitomycin for pyelocalyceal solution) is considered investigational for all other uses.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
Medicaid Coverage:
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Mitomycin for Pyelocalyceal Solution (Jelmyto)
Jelmyto (Mitomycin for Pyelocalyceal Solution)
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.
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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