LCD Reference Article Response To Comments Article

Response to Comments: White Cell Colony Stimulating Factors

A59284

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A59284
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Article Title
Response to Comments: White Cell Colony Stimulating Factors
Article Type
Response to Comments
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12/22/2022
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The comment period for the White Cell Colony Stimulating Factors DL37176 Local Coverage Determination (LCD) began on 9/1/22 and ended on 10/15/22. The notice period for L37176 begins on 12/22/22 and will become effective on 2/5/23.

The comment below was received from the provider community.

Response To Comments

Number Comment Response
1

Please accept this information in support of your coverage guidance in Proposed Local Coverage Determination DL37176.

Our organization is dedicated to addressing serious diseases with medicines that will not only help patients, but also will help reduce the social and economic burden of disease. For these reasons, we are supportive of the following:

Analysis of Evidence (Rationale for Determination)

We concur with the coverage guidance in DL37176:

“Some retrospective studies support safety and efficacy of same day administration, but also trend to a non-statistically significant increase in side effects with same day administration. In addition, other retrospective studies demonstrate a disadvantage to same day dosing. The National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2022 state that pegfilgrastim same day administration is supported by category one evidence, however there is data for and against same day dosing. The Food & Drug Administration (FDA) approved dosing schedule is still recommended by NCCN.

For patients who cannot return to the clinic for next-day administration, there is an FDA-approved delivery device available that can be applied the same day as chemotherapy in order to deliver the full dose of pegfilgrastim the following day (approximately 27 hours after application).

In consideration of the above, Pegfilgrastim should continue to be given according to FDA approved dosing schedule”.

In support of the analysis of evidence, we would like to offer the following additional data:

  • Concordance from independent authorities regarding the importance of next-day dosing
    • The FDA-approved labeling for Neulasta® (pegfilgrastim) as well as for all currently approved pegfilgrastim biosimilars, specifies drug delivery should occur at least 24 hours after chemotherapy administration.
    • The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Hematopoietic Growth Factors recommend the administration of G-CSF per FDA-approved dosing schedule a day after chemotherapy (category 1). Administration of pegfilgrastim on the day after chemotherapy resulted in less severe and shorter suppression of ANC compared with pegfilgrastim administration on the same day of chemotherapy.
  • Real-world evidence in support of next-day dosing
    • Pegfilgrastim is administered subcutaneously via a single-dose prefilled syringe for manual injection or for use with the on-body injector (OBI) for pegfilgrastim. A healthcare provider must fill the OBI with pegfilgrastim using the prefilled syringe and applies the OBI on the patient on the same-day as chemotherapy, with drug delivery of pegfilgrastim approximately 27 hours later, eliminating the need to return to a healthcare provider to receive a pegfilgrastim injection.
    • A multi-institutional, prospective observational study evaluated the incidence of febrile neutropenia (FN) patients receiving pegfilgrastim via the OBI versus other methods of FN prophylaxis. The study enrolled 2,575 patients with breast, lung, prostate cancer, or NHL receiving a chemotherapy regimen with a high risk of FN, or a regimen with intermediate risk of FN with ≥ 1 patient risk factor. The choice for FN prophylaxis was physician-driven: OBI (n=1,624) vs other FN prophylaxis options, which included pegfilgrastim or biosimilar pegfilgrastim PFS, short-acting G-CSF, or no G-CSF (n=951).* The study showed that patients receiving pegfilgrastim OBI had an FN incidence rate of 6.4% compared with an incidence rate of 9.4% observed in those receiving alternatives for FN prophylaxis.
    • A summary of randomized clinical studies and real-world evidence (RWE) evaluating the incidence of febrile neutropenia for same-day pegfilgrastim administration following chemotherapy compared with next-day pegfilgrastim administration.
    • *24% of patients in the other FN prophylaxis group (n=228) did not receive G-CSF prophylaxis in any cycle. The rate of FN for the remaining 723 patients was 10%.
  • Reliability of the OBI device when delivering next-day pegfilgrastim
    • OBI device performance was assessed in the prospective study. There were 6 reported OBI device failures out of 6,087 administrations (0.1% failure rate). Device failure was physician reported and defined as not functioning as intended.
    • Additional evidence of OBI reliability was shown in a combined analysis of a post-marketing commitment evaluating OBI medication error events reported to the European Medicines Agency between 2018 and 2021. The error reporting rate for the OBI was as low as 0.58% for 27,666 devices based on the rate calculated per OBI use.
    • Taken together, these real-world studies suggest the OBI delivers pegfilgrastim reliably and appropriately for FN prophylaxis with >99% reliable administrations for more than 30,000 OBI applications.

We are grateful for the opportunity to comment on the Proposed Local Coverage Determination (DL37176) and provide additional relevant data supporting the determination.

References were provided for review.

Thank you for your comments and support.

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Associated Documents

Medicare BPM Ch 15.50.2 SAD Determinations
Medicare BPM Ch 15.50.2
Related Local Coverage Documents
LCDs
L37176 - White Cell Colony Stimulating Factors
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Keywords

  • White Cell Colony Stimulating Factors
  • White Cell Colony
  • Stimulating Factors