5 januari 2024: Bron: Journal of Clinical Oncology 41, no. 2 (January 10, 2023) 170-172. En 
Biomedicines. 2023 Apr; 11(4): 1032. Published online 2023 Mar 27 Met dank aan Eddy.

Uit verschillende studies blijkt dat immuuntherapie met anti-PD medicijnen / checkpointremmers met een veel lagere dosis dan de standaard doses voorgeschreven in de richtlijnen nauwelijks effect heeft op de therapeutische resultaten maar wel minder bijwerkingen geven en vooral veel minder kosten. 

De ontwikkeling en het gebruik van immuuntherapie in het afgelopen 10 tot 15 jaar hebben geleid tot een drastische verbetering van de resultaten binnen vormen van bloedkanker zoals leukemie en melanomen en vormen van kanker met solide tumoren waaronder longkanker, blaaskanker maar ook mond- en keelkanker en borstkanker.
Dit betekent wel dat artsen moeten leren omgaan met een nieuw soort bijwerking want als immuuntherapie met anti-PD medicijnen / checkpointremmers of ook een andere vorm van immuuntherapie zoals CAR-T-celtherapie aanslaat dan kan dat tot heftige bijwerkingen leiden, zie voor bijwerkingen bij anti-PD medicijnen / checkpointremmers deze PDF van de ESMO. 

Daarnaast rekenen farmaceutische bedrijven voor hun vormen van anti-PD medicijnen / checkpointremmers hele hoge prijzen waardoor immuuntherapie bijna onbetaalbaar wordt. Met uiteraard ook grote gevolgen voor de ziekenhuizen en ziektekostenverzekeraars die deze vormen van immuuntherapie met anti-PD medicijnen / checkpointremmers  die goedgekeurd zijn, zoals bv pembrolizumab, nivolumab en avelumab om er maar een paar te noemen, gedwongen zijn te leveren. En een behandeling met immuuntherapie via anti-PD medicijnen / checkpointremmers in een commerciële buitenlandse kliniek is schreeuwend duur meestal.

Uit recente wetenschappelijke studies blijkt echter dat de standaard dosering voor immuuntherapieën met anti-PD medicijnen / checkpointremmers drastisch kan worden verlaagd zonder de effectiviteit ervan te schaden. Een doseringsverlaging zou dus ook leiden tot een belangrijke verlaging van de kosten, waardoor veel meer kankerpatiënten toegang zouden kunnen krijgen tot op immuuntherapie gebaseerde behandelingen.

Eddy die mij hier attent op maakte ziet dat in Duitsland daarop al is ingehaakt en al enkele jaren immuuntherapie wordt gegeven in veel lagere doseringen en dat de resultaten gewoon hetzelfde blijven (zo tussen de 25 en 35 procent reageert met minimaal een gedeeltelijke remissie blijkt uit verschillende studies) als met de hogere voorgeschreven doseringen. Maar de prijs voor een behandeling met immuuntherapie met anti-PD medicijnen / checkpointremmers in Duitsland is een kwart tot een 6e van de standaardprijs.  

Ik heb twee studies over effecten van lagere doseringen van immuuntherapie met anti-PD medicijnen / checkpointremmers die ik jullie wil voorleggen.

In dit eerste artikel / abstract beschrijven drie artsen, te weten Fausto Meriggi,1,* Alberto Zaniboni,1 and Anna Zaltieri2 de effecten van verlaging van de dosering van anti-PD medicijnen met referenties van de studies. Referenties van beide studies samengevat onderaan artikel:
 2023 Apr; 11(4): 1032.
Published online 2023 Mar 27. doi: 10.3390/biomedicines11041032
PMCID: PMC10136204
PMID: 37189650

Low-Dose Immunotherapy: Is It Just an Illusion?

Fausto Meriggi,1,* Alberto Zaniboni,1 and Anna Zaltieri2
Bruno Kaufmann Robbs, Academic Editor
Author information Article notes Copyright and License information PMC Disclaimer

Abstract

The development and use of immunotherapy in the last decade have led to a drastic improvement in results in the onco-haematological field. This has implied, on the one hand, the need for clinicians to manage a new type of adverse event and, on the other hand, a significant increase in costs. However, emerging scientific evidence suggests that, as with other drugs in the recent past, the registry dosage can be drastically reduced for immunotherapies without penalizing their effectiveness. This would also lead to an important reduction in costs, expanding the audience of cancer patients who could access immunotherapy-based treatments. In this “Commentary”, we analyze the available evidence of pharmacokinetics and pharmacodynamics and the most recent literature in favor of low-dose immunotherapy.

In het tweede artikel een studie gedaan bij mond- en keelkankerpatiënten, maar de auteurs vermelden ook andere studies bij andere vormen van kanker met lagere doseringen:

EDITORIALS

Cost Savings and Increased Access With Ultra-Low-Dose Immunotherapy

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Aaron P. Mitchell , MD, MPH1 and Daniel A. Goldstein , MD2,3,4,5Show More

In the article that accompanies this editorial, Patil et al1 reported findings from a randomized clinical trial of nivolumab for advanced head and neck cancer. This trial found a substantial overall survival benefit from the addition of nivolumab to a regimen combining cytotoxic (methotrexate) and targeted (erlotinib) therapies. These findings are most notable not for the magnitude of clinical benefit but for the dose of nivolumab used to achieve them; at a flat dose of 20 mg once every 3 weeks, this represents a small fraction of the doses approved by regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency. This trial was conducted in India, and the investigators present this alternative nivolumab dosing schedule as a viable method to substantially reduce drug costs and hence increase access to immunotherapy agents in resource-limited settings.

THE TAKEAWAY

  • In the article that accompanies this editorial, Patil et al1 reported results from a randomized clinical trial that demonstrates a significant and clinically meaningful benefit from incorporating ultra-low-dose nivolumab into the treatment of patients with advanced head and neck cancer. By using a small fraction of the nivolumab dose approved in the United States and Europe, this treatment regimen dramatically reduces the financial cost of immunotherapy, with the potential to increase access and improve patient outcomes in low- and middle-income countries.

The nivolumab dose in this trial is approximately 6% of the FDA-approved flat dose of 240 mg once every 2 weeks. The investigators were able to reduce costs through vial sharing, administering two full 20-mg treatments from each 40-mg vial of nivolumab. The resulting treatment costs were < 10% the cost of nivolumab (or pembrolizumab) monotherapy at FDA-approved doses.

AUTHOR CONTRIBUTIONS

Conception and design: All authors

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Cost Savings and Increased Access With Ultra-Low-Dose Immunotherapy

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Aaron P. Mitchell

Open Payments Link: https://openpaymentsdata.cms.gov/physician/574689

Daniel A. Goldstein

Stock and Other Ownership Interests: TailorMed, Vivio Health

Consulting or Advisory Role: Vivio Health

Research Funding: MSD (Inst), BMS (Inst), Janssen (Inst)

No other potential conflicts of interest were reported.

ACKNOWLEDGMENT

Memorial Sloan Kettering Cancer Center Support Grant No. P30 CA008748, NCI.

Referenties:

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immuuntherapie, anti-PD medicijnen, checkpointremmers, pembrolizumab, nivolumab, hoofd- en hals kanker, mond- en keelkanker, bijwerkingen


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