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

Mitchell, Aaron P.; Goldstein, Daniel A.

doi:10.1200/jco.22.01711

Cited by 19 publications

(8 citation statements)

References 21 publications

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“…To address this issue, a safer ultra-low dose ICPi protocol was developed and tested on 131 unselected stage IV cancer patients with 23 different histologic cancers who had exhausted all conventional treatments. The protocol maintained efficacy ( 34 ) and was also found to be more cost-effective than registered doses ( 35 ).…”

Section: Discussionmentioning

confidence: 95%

Severe autoimmune hemolytic anemia following immunotherapy with checkpoint inhibitors in two patients with metastatic melanoma: a case report

Fetter,

Fietz,

Bertlich

et al. 2024

Front. Immunol.

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IntroductionOver the past decade, immune checkpoint inhibitors such as antibodies against cytotoxicity T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have become an important armamentarium against a broad spectrum of malignancies. However, these specific inhibitors can cause adverse autoimmune reactions by impairing self-tolerance. Hematologic side effects of immune checkpoint inhibitors, including autoimmune hemolytic anemia (AIHA), are rare but can be life-threatening.Case reportHerein, we report two patients on immune checkpoint inhibitors for metastatic melanoma who developed AIHA with symptoms of dyspnea and fatigue. In the first patient, symptoms alleviated after discontinuation of combined anti CTLA-4 and anti-PD-1 therapy, initiation of corticosteroids and application of a single red blood cell transfusion. Due to subsequent progress of melanoma, combinational anti-PD-1 and tyrosine kinase inhibitor therapy was initiated based on multidisciplinary tumor board decision. After two months, she again developed the described hematological and clinical signs of AIHA leading to cessation of anti-PD-1 therapy and initiation of corticosteroids, which again resulted in an alleviation of her symptoms. Due to further progression, the patient received dacarbazine for several months before she decided to stop any therapy other than palliative supportive care. In the second patient, discontinuation of anti-PD-1 therapy and initiation of corticosteroids entailed a complete alleviation of his symptoms. After refusing chemotherapy due to subsequent melanoma progression, he received radiotherapy of bone metastases and is currently enrolled in a clinical trial. The patient did not develop AIHA ever since.ConclusionHematologic immune-related adverse events due to treatment with immune checkpoint inhibitors are rare but can have life-threatening consequences. If dyspnea and other clinical symptoms are present, AIHA should be considered as a potential cause and treated promptly in a multidisciplinary setting. An expanded comprehension of risk factors and pathogenesis of AIHA is needed to identify high-risk patients beforehand, leading to more effective predictive and reactive treatment approaches.

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Section: Discussionmentioning

confidence: 95%

Severe autoimmune hemolytic anemia following immunotherapy with checkpoint inhibitors in two patients with metastatic melanoma: a case report

Fetter,

Fietz,

Bertlich

et al. 2024

Front. Immunol.

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“…The scientific literature available to date shows that too often there are post-dose modifications of the approved regimens for several anticancer drugs, such as anti-PD-1 or anti-PD-L1 antibodies, without negative repercussions on efficacy and costs, while there is often a gain in terms of safety and economic savings. We also know of similar evidence transferable to numerous other anticancer drugs with the possibility of reducing the approved dose, such as for abiraterone acetate in prostate cancer [ 26 , 27 , 28 ]. In clinical practice, there is today a strong scientific and social rationale to support the further development of low-dose ICI-containing regimens, and we fully share the principles that motivate these studies, especially in an era of increasing economic hardship.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Immunotherapy: Is It Just an Illusion?

2023

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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.

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“…For example, the earliest use-cases for IVPE trials were to research whether a lower dose or shorter duration of treatment would be as effective with fewer side-effects [22]. Immunotherapies such as pembrolizumab or nivolumab currently generate approximately US $30 billion in annual sales [23], but could be effective at less than 10% of the dose [24] or discontinued early after a complete response [25]. Conducting such de-escalation or discontinuation trials can unlock billions of dollars in savings from pharmaceutical budgets to fund generic drug repurposing and also improve access to these essential medicines globally.…”

Section: A New Financial Model For Developing Affordable Therapiesmentioning

confidence: 99%

Using Interventional Pharmacoeconomic Clinical Trials and Outcomes-Based Contracts to Repurpose Generic Drugs with Cost-Savings

Kerdemelidis

2024

Preprint

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One of the greatest barriers to the repurposing of generic drugs is the lack of a financial model to recover the costs of clinical trials. Academics have acknowledged this “problem of new uses” for many years.[1] And so despite their great medical and cost-saving potential, repurposed generic drugs are referred to as “financial orphans” [2], “highly non-excludable therapies” [3], or “unmonopolisable therapies” [4], that are extremely unlikely to receive the funding needed for regulatory approval. One proposed solution to the problem of new uses is to restrict off-label use and allow reimbursement of the repurposed generic at a higher price for the new indication.[5] Another option is the increased public funding of clinical trials. However, this has been politically, legally and practically difficult to achieve. A financially-innovative solution to the problem of new uses is to leverage the immediate and future cost savings of health insurers. In particular, the novel discipline of interventional pharmacoeconomics (IVPE) allows for self-funding clinical trials by comparing a low-cost intervention (such as a repurposed generic) to expensive standard of care.[6] The cost savings from patients taking the low-cost intervention in one arm can exceed the cost of the trial itself, even if it fails, which means there is no financial risk. However, an IVPE trial requires the substitution of the low-cost intervention for expensive standard of care, and may not be appropriate for all repurposing opportunities, especially where no expensive comparator intervention is available. For this latter situation, it is possible to use outcomes-based incentives similar to prizes called Pay-For-Success (PFS) contracts, Advance Market Commitments (AMC) [7], or Social Impact Bonds (SIBs).[8] Such “prize-like” incentives have been used to accelerate the development of Covid vaccines [9] and antibiotics [10], but not yet for repurposing generic drugs. The IVPE concept has been called a ‘revolving research fund’ in Europe, where the cost-savings of clinical trials are used to fund additional research.[11] Similar cost-saving trials are also being funded by a consortium of health insurers in the Netherlands on a case-by-case basis.[12] It is hereby proposed that establishment of an IVPE + AMC fund by private or public health insurers can develop repurposed generic drugs, which can address the “financial toxicity” of new patented drugs while improving patient outcomes.[13] There are many known IVPE opportunities, for example, comparing repurposed generic IV ketamine to patented esketamine for treatment resistant depression [14] or off-label bevacizumab (Avastin) to ranibizumab (Lucentis) for macular degeneration.[15] There is an opportunity to discover and medically de-risk additional IVPE repurposing candidates for self-funding trials by conducting retrospective studies and meta-analyses of medical records and clinical data.

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

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

Cited by 19 publications

References 21 publications

Severe autoimmune hemolytic anemia following immunotherapy with checkpoint inhibitors in two patients with metastatic melanoma: a case report

Severe autoimmune hemolytic anemia following immunotherapy with checkpoint inhibitors in two patients with metastatic melanoma: a case report

Low-Dose Immunotherapy: Is It Just an Illusion?

Using Interventional Pharmacoeconomic Clinical Trials and Outcomes-Based Contracts to Repurpose Generic Drugs with Cost-Savings

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