Evidence map›Paper›PMID 32393603›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020

Differentiation Syndrome with Ivosidenib and Enasidenib Treatment in Patients with Relapsed or Refractory IDH-Mutated AML: A U.S. Food and Drug Administration Systematic Analysis.

Kelly J Norsworthy, Flora Mulkey, Emma C Scott, Ashley F Ward, Donna Przepiorka, Rosane Charlab, Sarah E Dorff, Albert Deisseroth, Dickran Kazandjian, Rajeshwari Sridhara and 4 more

Registry-linked trialOpen access · bronzeAbstract readComment
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07283094 (FHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid Leukemia), which is not on this map. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07283094 phase1recruitingnot on this mapstarted 2026, after this paper: background citation

FHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid Leukemia

TypeinterventionalSponsorMontefiore Medical CenterRan2026 to 2030Enrolled33ConditionsAcute Myeloid Leukemia, Myelodysplastic SyndromeArmsDecitabine, Venetoclax, FHD-286
3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
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  7. FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with aClinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
  8. Review
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  10. Article
  11. Review
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  14. Article
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  19. FDA Approval Summary: Ivosidenib for Treatment of Adult Patients with Relapsed/Refractory Myelodysplastic Syndrome with an IDH1 Mutation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  20. Review

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Kelly J NorsworthyCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. kelly.norsworthy@fda.hhs.gov.
Flora MulkeyCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Emma C ScottCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Ashley F WardCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.ORCID 0000-0001-6535-8132
Donna PrzepiorkaCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Rosane CharlabCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Sarah E DorffCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Albert DeisserothCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Dickran KazandjianCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Rajeshwari SridharaCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Julia A BeaverCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Ann T FarrellCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
R Angelo de ClaroCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Richard PazdurOncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, Maryland.
Center for Drug Evaluation and Research · USUnited States Food and Drug Administration · US

Funding

Intramural FDA HHS FD999999
6 · The paper itself

Abstract

purposeDifferentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with EXPERIMENTAL

designDuring FDA review of marketing applications for ivosidenib and enasidenib, data from pivotal trials were queried to identify cases of DS in patients with relapsed or refractory (R/R) AML. One hundred seventy-nine patients with R/R AML received ivosidenib and 214 received enasidenib. Adverse events, labs, and vital signs in the first 90 days of treatment were screened per diagnostic criteria, and narratives were reviewed to adjudicate DS cases.

resultsWe identified 72 of 179 (40%) potential cases for ivosidenib and 86 of 214 (40%) for enasidenib; 34 of 179 (19%) and 41 of 214 (19%) were adjudicated as DS. Leukocytosis was present in 79% and 61% of cases, respectively. Median (range) time to onset was 20 (1-78) and 19 (1-86) days. Grade ≥ 3 adverse reactions occurred in 68% and 66%; 6% and 5% were fatal. Univariate analyses suggested baseline bone marrow blasts ≥ 48% and peripheral blood blasts ≥ 25% and 15% for ivosidenib and enasidenib, respectively, were associated with increased risk of DS. Complete remission (CR) + CR with partial hematologic recovery rates were lower in patients with versus without DS [ivosidenib 18% (95% confidence interval, 7%-35%) vs. 36% (28%-45%); enasidenib 18% (7%-33%) vs. 25% (18%-32%)].

conclusionsDS is a common and potentially fatal adverse reaction of IDH inhibitors, and use of standardized diagnostic criteria may aid in earlier diagnosis and treatment.

Indexed as

Isocitrate DehydrogenaseLeukemia, Myeloid, AcuteAminopyridinesGlycineHumansMutationPyridinesTriazinesUnited StatesUnited States Food and Drug AdministrationAminopyridinesenasidenibGlycineIsocitrate DehydrogenaseivosidenibPyridinesTriazines

Identifiers

PMID32393603
PMCPMC7442588
OpenAlexW3021352118

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.