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Three US Food and Drug Administration-approved therapies for chronic GVHD.

ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a major immunologic complication of allogeneic hematopoietic cell transplantation. cGVHD involves multiple organs, reduces quality of life, and often requires prolonged therapy with glucocorticoids, causing severe side effects. After 4 decades of testing multiple therapeutic approaches, ibrutinib, belumosudil, and ruxolitinib were US Food and Drug Administration approved for cGVHD in the last 4 years. Here we put a spotlight on their mechanisms of action, studies that led to approval, and their future role in cGVHD.

SUBMITTER: Zeiser R

PROVIDER: S-EPMC8931512 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Three US Food and Drug Administration-approved therapies for chronic GVHD.

Zeiser Robert R Lee Stephanie J SJ

Blood 20220301 11

Chronic graft-versus-host disease (cGVHD) is a major immunologic complication of allogeneic hematopoietic cell transplantation. cGVHD involves multiple organs, reduces quality of life, and often requires prolonged therapy with glucocorticoids, causing severe side effects. After 4 decades of testing multiple therapeutic approaches, ibrutinib, belumosudil, and ruxolitinib were US Food and Drug Administration approved for cGVHD in the last 4 years. Here we put a spotlight on their mechanisms of act ...[more]

PMID: 35081254

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Project description:ImportanceFor patients with cancer treated with palliative intent, quality of life (QOL) is a critical aspect of treatment decision-making, alongside survival. However, regulatory approval can be based solely on survival measures or antitumor activities, without QOL evidence.ObjectiveTo investigate whether recently approved oncology therapies demonstrate clinically meaningful improvements in QOL.Evidence reviewThis systematic review study identified oncology drug indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) from January 2006 to December 2017 and supporting clinical trials (QOL publications identified to October 2019). Indications were evaluated for the presence of published QOL evidence; QOL benefits according to the American Society of Clinical Oncology Value Framework version 2.0 (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) QOL bonus criteria; and clinically meaningful improvements in QOL beyond minimal clinically important differences. Hematology trials were not evaluated by ESMO-MCBS. Associations between QOL evidence and approval year were examined using logistic regression models.FindingsIn total, 214 FDA-approved (77 [36%] hematological) and 170 EMA-approved (52 [31%] hematological) indications were included. QOL evidence was published for 40% and 58% of FDA- and EMA-approved indications, respectively. QOL bonus criterion for ASCO-VF and ESMO-MCBS was met in 13% and 17% of FDA-approved and 21% and 24% of EMA-approved indications, respectively. Clinically meaningful improvements in QOL beyond minimal clinically important differences were noted in 6% and 11% of FDA- and EMA-approved indications, respectively. Availability of published QOL evidence at the time of approval increased over time for EMA (odds ratio [OR], 1.13; P = .03), however not for FDA (OR, 1.10; P = .12). Over time, no increase in awarded QOL bonuses or clinically meaningful improvements in QOL were found.Conclusions and relevanceThe findings of this systematic review suggest that approved systemic oncology therapies often do not have published evidence to suggest QOL improvement, despite its recognized importance. Of indications with evidence of statistical improvement, few have demonstrated clinically meaningful improvements.

Project description:BackgroundThe cost of new anticancer drugs is rising. We aimed to assess the clinical benefit and price of anti-cancer drugs approved by the US Food and Drug Administration (FDA) for advanced gastrointestinal cancers.MethodsDrugs approved between 2006 and 2017 for advanced GI malignancies were identified from FDA.gov, and their updated supporting trial data were searched. Incremental clinical benefit was quantified by using ESMO Magnitude of Clinical Benefit Scale version 1.1 (grade 0-5) and ASCO Value Framework version 2 (score range -20 to 180). Higher scores indicate larger net benefit, and substantial benefit was defined as score 4 or 5 by the European Society for Medical Oncology (ESMO). The Micromedex REDBOOK was used to estimate the monthly average wholesale price (AWP) and total drug price (TDP) over the median treatment duration per patient. Clinical benefit, AWP and TDP of each drug class were assessed.ResultsIn total, 16 GI cancer drugs received FDA approval for 24 indications, including five monoclonal antibodies (mAbs), five oral targeted therapies (TT), two immunotherapeutics (IO), three cytotoxic chemotherapies (CT), and one recombinant fusion protein (aflibercept). Most supporting trials (82%) reported overall survival benefit of less than 3 months and no significant improvement in quality of life. Only five agents (including one TT and one IO) with 21% the of approved indications met the ESMO's threshold of substantial clinical benefit. Median incremental benefit scores of TT and IO were comparable to other drug classes. However their median TDP was much higher at $153 402 and $98 208, respectively, compared to $30 330 USD per patient for CT. The estimated TDP did not correlate with clinical benefit scores.ConclusionMost FDA-approved gastrointestinal cancer drugs do not meet the ESMO threshold of substantial clinical benefit. TT and IO are estimated to carry significant drug costs, and further cost analysis of these drugs is urgently needed.

Dataset Information

Three US Food and Drug Administration-approved therapies for chronic GVHD.

Publications

Three US Food and Drug Administration-approved therapies for chronic GVHD.

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