Evaluating Recent Drug Approvals for Hematologic Malignancies Utilizing the New European Society of Medical Oncology Magnitude of Clinical Benefit Scale for Hematology (ESMO-MCBS:H)

Introduction:

Over the last decade, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have steadily leaned towards granting regulatory approval based on earlier phase trials and surrogate endpoints. Despite obtaining regulatory approval, many countries hold additional standards to assess the value of a new drug approval. The ESMO-MCBS is a tool created to evaluate the values and reduce bias or hype of drug approvals using various metrics: efficacy, quality of life, and duration of response. In 2023, the ESMO-MCBS:H was created for hematological malignancies. We aimed to evaluate recent drug approvals using the new ESMO-MCBS:H criteria for hematologic malignancies.

Methods:

We included all drugs approved for a hematologic malignancy between 2019 and 2024. Drugs were assessed using ESMO-MCBS:H forms 2a, 2b, 2c, or 3 depending on the trial type and primary endpoints leading to drug approval. Approvals were independently scored by two reviewers with a third reviewer to adjudicate scoring differences.

Results:

66 drugs were approved by either FDA or EMA during this time. 88% (n=58) were approved by both EMA and FDA, 12% (n=8) by FDA alone. No drugs were approved by the EMA alone without preceding or subsequent FDA approval. 4 drug approvals were for pediatric indications. 36 approvals (n=35/66, 53 %) were based on early phase 1 and/or 2 trial data. Approvals were for leukemias (n=16; 24%), lymphomas (n=25, 38%), myeloma (n=18, 27%), or CLL/SLL (n=6; 9%). 13% of approvals (n=9/66) were for drugs with a biomarker matched indication.

Substantial benefit criteria were met by 17 of 66 approvals (26%). Substantial benefit criteria were met by 0% (N=0/8) of drug indication by approved by FDA alone versus 29% of drugs approved by both the FDA and EMA (n=17/58), however was not statistically significant (p=0.08).

Approvals based on early phase (phase 1 and/or 2) trials met criteria in 17% (n=6/35) of trials and 36% of later phase (phase 3) trials met criteria (n=11/31) without statistical significance (p=0.09).

No significant difference in approvals meeting substantial benefit were seen for biomarker matched therapies (33%; n=3/9) versus unmatched therapies (25%; n=14/57) (p=0.58).

No therapies approved for a pediatric indication met criteria for substantial benefit (n=0/4).

Conclusion:

Few drugs approved by both agencies met the rigorous ESMO-MCBS:H criteria for substantial benefit. Recent approvals meeting substantial benefit criteria were not statistically correlated with approval agency, phase of trial utilized for approval, or biomarker selection of therapies. Drug approvals must balance proven benefit to access to innovative and new therapies.

Moyers:Clinical Care Options: Speakers Bureau; Replimmune and Pfizer: Membership on an entity's Board of Directors or advisory committees. Benjamin:Astellas, Eisai, Seagen: Membership on an entity's Board of Directors or advisory committees; Merck: Speakers Bureau; Merck, Seagen: Other: Travel Accomodations.