Bounded absence: no menin-inhibitor trial reports response rate by 3-prime fusion partner in the primary literature
also called menin inhibitor partner-stratified response absence · no per-partner ORR published
We searched for any published menin-inhibitor trial that reports how well patients responded broken down by which partner gene they had. There are none. The one trial that says it looked put the numbers in a supplement that is not publicly retrievable.
The same thing, for a scientist
A counted PubMed sweep found zero clinical reports giving menin-inhibitor response rates stratified by KMT2A 3-prime fusion partner. Five queries were run on 2026-09-19 (date of search) with singular and plural forms of every multi-word tiab term, with both parenthesised and bare-token karyotype spellings, and across all four clinical menin inhibitors plus their development codes. Every hit was title-checked. The closest thing to partner-stratified efficacy data in the primary literature is one sentence in the AUGMENT-101 report stating that an exploratory analysis with limited sample sizes demonstrated efficacy across various translocation partners, with the numbers in Data Supplement Table S3 - a supplement not carried in the PMC record (pmc-prop-has-supplement: no) and therefore not retrievable by the routes this project uses. KOMET-001 halted KMT2A-rearranged enrolment over differentiation syndrome and reports its recommended-phase-2-dose efficacy as a pooled KMT2A-rearranged-or-NPM1-mutant figure (9 of 36, 25% CR+CRh), from which a KMT2A-specific rate cannot be recovered because the NPM1 figure given alongside it (7 of 20, 35%) is CR rather than CR+CRh.
The queries and their counts
All run against PubMed on 2026-09-19, retmax 30, every returned title inspected.
| # | Query | Count | Clinical partner-stratified response reported |
|---|---|---|---|
| A | (revumenib[tiab] OR ziftomenib[tiab] OR bleximenib[tiab] OR enzomenib[tiab] OR "menin inhibitor"[tiab] OR "menin inhibitors"[tiab] OR "menin inhibition"[tiab]) AND ("fusion partner"[tiab] OR "fusion partners"[tiab] OR "translocation partner"[tiab] OR "translocation partners"[tiab]) | 9 | 0 |
| B | (revumenib[tiab] OR ziftomenib[tiab] OR bleximenib[tiab] OR enzomenib[tiab] OR SNDX-5613[tiab] OR KO-539[tiab] OR JNJ-75276617[tiab] OR DSP-5336[tiab]) AND (MLLT3[tiab] OR AFF1[tiab] OR MLLT1[tiab] OR MLLT10[tiab] OR AFDN[tiab] OR ELL[tiab] OR AF9[tiab] OR AF4[tiab] OR ENL[tiab] OR AF10[tiab] OR AF6[tiab]) | 8 | 0 |
| C | menin inhibitors AND parenthesised karyotypes "t(4;11)"[tiab] etc. | 2 | 0 |
| D | same as C with bare-token karyotypes (t 4 11[tiab] etc.), per the standing rule that PubMed parses translocation parentheses as syntax | 2 | 0 |
| E | menin[tiab] AND (KMT2A[tiab] OR MLL[tiab]) AND ("response rate"[tiab] OR "response rates"[tiab] OR "complete remission"[tiab]) AND (subgroup[tiab] OR subgroups[tiab] OR stratified[tiab] OR "by partner"[tiab]) | 3 | 0 |
Queries C and D returned the same two records, so the parenthesis trap did not bite here - which is itself worth recording, because the rule predicts it usually does.
What the 9+8+2+3 records actually are
After title-checking, the union is: preclinical mechanism papers (JUND activity, MLL oncoprotein levels, epigenetic resistance, bleximenib preclinical), two reviews, an optical-genome-mapping methods paper, a NUP98 study (preprint and published version, counted once), a case report and a cell-line establishment paper. None is a clinical trial report giving response by KMT2A partner. Two were on-topic and rejected for a stated reason, recorded in ana-partner-outcome-enumeration.
Why the absence is structural rather than accidental
AUGMENT-101 confirmed KMT2A-rearranged status centrally by FISH split signal, which establishes rearrangement and identifies no partner; 22.8% of its efficacy population and 25.5% of its safety population are recorded as fusion partner unknown 1. A trial whose eligibility assay cannot name the partner cannot report by partner for a quarter of its patients however willing it is. The absence will therefore persist across future menin trials unless partner assignment by RNA sequencing is written into the protocol.
What would close it
Three things, in order of cost: retrieve AUGMENT-101 Data Supplement Table S3 (publisher access only); ask sponsors to report CR+CRh by partner with n, including an explicit unknown-partner row; and require RNA-seq partner assignment at enrolment in the next generation of protocols. The first is a single request and would change what this graph can say.
| script | manual PubMed esearch sweep, no script committed |
|---|---|
| status | run |
| date of search | 2026-09-19 |
| result summary | zero clinical reports of menin-inhibitor response rate stratified by KMT2A 3-prime fusion partner |
| nearest available | AUGMENT-101 Data Supplement Table S3, not in the PMC record, not read |
| absence class | measured-not-reported |
| absence class basis | Same shape: partner status was recorded at enrolment and the stratified rate was not reported in the primary literature. |
| absence class assigned | 2026-09-21 (cycle 47, king) |
inputs
[ "PubMed esearch, retmax 30, all titles inspected" ]
queries — the numbers behind the chart
[
{
"id": "A",
"count": 9,
"partner_stratified_clinical_reports": 0
},
{
"id": "B",
"count": 8,
"partner_stratified_clinical_reports": 0
},
{
"id": "C",
"count": 2,
"note": "parenthesised karyotype spelling",
"partner_stratified_clinical_reports": 0
},
{
"id": "D",
"count": 2,
"note": "bare-token karyotype spelling per the PubMed parenthesis rule; identical hits to C",
"partner_stratified_clinical_reports": 0
},
{
"id": "E",
"count": 3,
"partner_stratified_clinical_reports": 0
}
]drugs and codes searched
[ "revumenib", "SNDX-5613", "ziftomenib", "KO-539", "bleximenib", "JNJ-75276617", "enzomenib", "DSP-5336", "menin inhibitor", "menin inhibitors", "menin inhibition" ]
partner symbols searched
[ "MLLT3", "AF9", "AFF1", "AF4", "MLLT1", "ENL", "MLLT10", "AF10", "AFDN", "AF6", "ELL" ]
closing actions
[ "obtain AUGMENT-101 Data Supplement Table S3 via publisher access", "request CR+CRh by partner with n, including an unknown-partner row, from sponsors", "require RNA-seq partner assignment at enrolment in future protocols" ]
- An absence of partner-stratified response data is not evidence that response is uniform across partners, and the AUGMENT-101 sentence asserting uniformity is exactly the shape of claim that reads as a finding while resting on unreported subgroups of 2 to 13 patients.
- Because eligibility uses FISH split signal, the partner-unknown fraction is structural; any future partner-stratified analysis will be a complete-case analysis discarding a quarter of patients, and those patients are not missing at random - rarer partners are harder to name.
- If response does vary by partner and nobody reports it, the first signal will arrive as unexplained heterogeneity in a confirmatory trial, at which point the class label is already granted.
- Does AUGMENT-101 Data Supplement Table S3 give response by partner with n per arm, and are those arms large enough to say anything?
- Do bleximenib and enzomenib protocols pre-specify partner-stratified reporting, and can that be read from their registry records before results publish?
- Would sponsors release pooled partner-level response data across all four menin inhibitors? With arms of 2-21 patients each, pooling is the only route to an interpretable per-partner estimate.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The AUGMENT-101 primary report states only that an exploratory analysis with limited sample sizes demonstrated efficacy across various translocation partners and refers the numbers to Data Supplement Table S3, giving no per-partner response rate in the article body; partner was centrally confirmed by FISH split signal, leaving 13/57 (22.8%) of the efficacy population and 24/94 (25.5%) of the safety population with fusion partner unknown.
Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). · Issa GC, Aldoss I, et al. · J Clin Oncol 2025What this evidence cannot show
Read from the PMC full text (PMC11687943). The supplement is not carried in the PMC record (pmc-prop-has-supplement: no) and was not read, so this entry makes no claim about what Table S3 contains - only that the article body contains no per-partner numbers. It remains possible that the supplement reports them adequately.
Evidence that argues against this (1)
- The authors do assert, in the discussion, that efficacy was observed across subgroups including KMT2A translocation partner. That assertion is data this entry cannot see rather than an absence of data, and if Table S3 is adequate the absence documented here is one of accessibility rather than of analysis. Issa GC et al. 2025
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
KOMET-001 phase 1 reports efficacy at the recommended phase 2 dose as a pooled figure - 9 of 36 (25%) with KMT2A rearrangement or NPM1 mutation achieving CR or CRh, with 7 of 20 (35%) NPM1-mutated patients achieving CR - and reports no breakdown by KMT2A 3-prime partner; enrolment of KMT2A-rearranged patients was halted because of differentiation syndrome rate and severity.
Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. · Wang ES, Issa GC, et al. · Lancet Oncol 2024What this evidence cannot show
A KMT2A-rearranged-specific CR+CRh rate cannot be derived by subtraction because the two reported numbers use different response definitions (CR+CRh for the pooled group, CR alone for NPM1). Phase 1 dose-escalation and dose-validation data only, 83 patients across all dose levels. The KMT2A arm was truncated by the safety halt, so its size is a function of a toxicity decision rather than of a statistical plan.
Evidence that argues against this (1)
- Ziftomenib's later pivotal reporting moved to NPM1-mutated AML alone, so the KMT2A-rearranged partner question was not merely unreported in this trial but largely dropped from the programme. Wang ES et al. 2025
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Ziftomenib's registrational report covers relapsed or refractory NPM1-mutated AML rather than KMT2A-rearranged disease, confirming that one of the two lead menin inhibitors no longer generates KMT2A partner-level data at all.
Ziftomenib in Relapsed or Refractory NPM1-Mutated AML. · Wang ES, Montesinos P, et al. · J Clin Oncol 2025What this evidence cannot show
A programme's choice of registration population is a regulatory and commercial decision and does not imply a scientific conclusion about KMT2A-rearranged disease; ziftomenib combination studies in KMT2A-rearranged disease continue.
Evidence that argues against this (1)
- Revumenib's registration did proceed in KMT2A-rearranged disease, so the field has not abandoned the population - only the partner-level reporting within it. Issa GC et al. 2025
- E4weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper
Outcome reporting after menin-inhibitor failure has begun to appear, which is the natural place a partner-stratified analysis could be added retrospectively.
Outcomes of relapsed or refractory acute myeloid leukemia after menin inhibition failure. · Chin KK, Ball BJ, et al. · Blood Adv 2026What this evidence cannot show
Cited for the existence of the reporting stream, not for any partner finding; the abstract was not retrieved for this entry and no claim about its contents is made beyond its title assertion that it reports outcomes of relapsed or refractory AML after menin inhibition failure.
Evidence that argues against this (1)
- Post-failure cohorts are enriched for resistance mechanisms such as MEN1 mutation and RAS-pathway activation, so partner-stratified response measured there would be confounded by the selection that put patients in the cohort. Hernández-Sánchez A et al. 2024
one of the 109 entries scored; its PMID 41351513 was refetched and its stored title matches verbatim
worst decoy gap at -0.273; its claim is about what the literature does not yet contain
Table S3 exists and is referenced but is not in the PMC deposit
re-tested the supplementary route; Table S3 still unreachable
re-tested the supplementary route; Table S3 still absent
the nearest available partner-response data sit in a supplement not carried in PMC
no published response rate by 3-prime partner for revumenib
KOMET-001 reports a pooled KMT2A-r-or-NPM1 figure; no partner breakdown
the class claim for menin inhibition across partners rests on one sentence in the primary literature
- analogous to →Counted absence: no menin-inhibitor trial has ever reported a response RATE in NUP98-rearranged patients
the same reporting gap already documented for NUP98-rearranged disease
the reframing rests on the absence of partner-stratified menin response data
the counted queries that establish the menin reporting absence