Table 1.

Summary of patient outcomes with TP53-mutated myeloid disease from select clinical trials

Study (phase) experimental [E] and comparator arm [C]Patient populationSample size (all, TP53ma)Median ageSex (% female)CR (%)b (overall, TP53m)TP53 median VAF (%)Median OS (months)
Phase 310,11,53
CPX-351[E] 		60-75 years with therapy-related AML/previous MDS or MDS karyotype including those pretreated with HMA 153, 24 68 39 37, 29  Overall: 9.33>
(CI 6.37-11.86)
TP53m: 4.53 
7 + 3 [C] 156, 35 68 38 26, 34  Overall: 5.95
(CI 4.99-7.75)
TP53m: 5.13 
AML 19- Phase 3, randomized12
CPX-351 [E] 		HR-MDS and AML 105, 43 57 43 40  TP53m: 7;
TP53 WT: 28
Overall: 13.3 
FLAG-Ida [C] 82, 32 55 41 51  Overall: 11.4 
Decitabine 10 days14  MDS, AML, and relapsed AML
MDS
AML
Relapsed AML 		116, 21
26, 9
54, 9
36, 3 		74 41 53, 100  TP53m: 12.7
TP53 WT: 15.4 
Phase 2, randomized15
Decitabine 10 days [E] 		AML ineligible for IC 71, 24
43, 17 		77  30, 41 50 Overall: 6 (IQR 1 · 9-11 · 7); TP53m 4.9 (3 · 1-10 · 6) 
Decitabine 5 days [C]  28, 7 78  29, 14 23 Overall: 5.5 (IQR 2 · 1-11 · 7); TP53m 5.5 (IQR 1 · 9-8 · 5) 
ASCERTAINh trial–phase 3, randomized16,17
Seq A:
Oral dec C1 → IV dec C2
Seq B:
IV dec C1 → oral dec C2 		Int or high-risk MDS
CMML
AML 20-30% blastsc 		133, 44 -
BA 32%;
MA 68%
66
67 		70
72 		36
33 		25  TP53m: 25.5
(BA: 13, MA: 29.2)
TP53 WT: 33.7 
VIALE A trial18-20
phase 3, randomized
Azacitidine + venetoclax [E] 		AML ineligible for intensive chemo 431, 52
286, 38 		76 40 66d, 55  Overall: 14.7, 5.17e 
Azacitidine [C]  145, 14 76 40 28, 0  Overall: 9.6, 4.9 
Phase 1b27
Magrolimab + azacitidine 		Untreated AML ineligible for IC 87, 72 73 43 32, 32 61 Overall: 10.8;
TP53m: 9.8 
Phase 1b
Magrolimab + azacitidine28  		Untreated MDS 95, 25 69 35 33, 40 41 Overall: NR;
TP53m: 16.33 
Phase 1b/2
Eprenetapopt + azacitidine (2)33  		HMA naïve— TP53-mutated high-risk oligoblastic AML, MDS/AML, MDS and MDS/MPN, CMML 55 66 53 44f 21 10.8 (95% CI, 8.1 to 13.4) 
Phase 2
Eprenetapopt + azacitidine34  		HMA-naïve TP53-mutated AML, MDS/AML, CMML 52 74 48 57: MDS
36: AML 		23 12.1 (MDS)
10.4 (AML) 
Phase 135
Eprenetapopt + venetoclax + azacitidine [E] 		MDS previously transplanted or treated with HMA
Untreated TP53-mutated AML 		49 (40 BA)
43 		67 47 38 41 7.3 (95%
CI 5 · 6-9 · 8) 
Eprenetapopt + azacitidine [C] 6 69 67 17   
Phase 1b38
Cohort A: tagraxofusp + AZA (MDS)
Cohort B: tagraxofusp + AZA + ven (AML) 1L and RR
Tagraxofusp + AZA + ven (AML) 1L only 		New and R/R AML CD123 positive (declined/ ineligible for IC)
HR-MDS for cohort A 		82
19
37
26, 13 (multi-hit TP53 m-9) 		62
70
71 		37
41
39 		(69, 54)g  Overall: 14; TP53m: 9.5 
MBG45341
Phase 1b
Sabatolimab + HMA (decitabine or azacitidine) 		Untreated HR/VHR MDS or CMML 68, 14 70 (MDS)
68 (CMML) 		45 (MDS)
20
(CMML) 		20, 29  Overall: 26.7 
STIMULUS-MDS 1
Phase 2
Sabatolimab + HMA [E] 		Untreated intermediate/high/very HR-MDS 127, 41
65, 22 		73 37 23  Overall: 19 
HMA alone [C] 62, 19 73 27 21  Overall: 18 
Phase 142,44
SL-172154 (19)
SL-172154 + azacitidine (18) 		R/R AML or MDS
TP53m-MDS (for SL-AZA) 		37, 14
19
18 		70 38 1 CR and 1 marrow
CR in TP53m 		  
Study (phase) experimental [E] and comparator arm [C]Patient populationSample size (all, TP53ma)Median ageSex (% female)CR (%)b (overall, TP53m)TP53 median VAF (%)Median OS (months)
Phase 310,11,53
CPX-351[E] 		60-75 years with therapy-related AML/previous MDS or MDS karyotype including those pretreated with HMA 153, 24 68 39 37, 29  Overall: 9.33>
(CI 6.37-11.86)
TP53m: 4.53 
7 + 3 [C] 156, 35 68 38 26, 34  Overall: 5.95
(CI 4.99-7.75)
TP53m: 5.13 
AML 19- Phase 3, randomized12
CPX-351 [E] 		HR-MDS and AML 105, 43 57 43 40  TP53m: 7;
TP53 WT: 28
Overall: 13.3 
FLAG-Ida [C] 82, 32 55 41 51  Overall: 11.4 
Decitabine 10 days14  MDS, AML, and relapsed AML
MDS
AML
Relapsed AML 		116, 21
26, 9
54, 9
36, 3 		74 41 53, 100  TP53m: 12.7
TP53 WT: 15.4 
Phase 2, randomized15
Decitabine 10 days [E] 		AML ineligible for IC 71, 24
43, 17 		77  30, 41 50 Overall: 6 (IQR 1 · 9-11 · 7); TP53m 4.9 (3 · 1-10 · 6) 
Decitabine 5 days [C]  28, 7 78  29, 14 23 Overall: 5.5 (IQR 2 · 1-11 · 7); TP53m 5.5 (IQR 1 · 9-8 · 5) 
ASCERTAINh trial–phase 3, randomized16,17
Seq A:
Oral dec C1 → IV dec C2
Seq B:
IV dec C1 → oral dec C2 		Int or high-risk MDS
CMML
AML 20-30% blastsc 		133, 44 -
BA 32%;
MA 68%
66
67 		70
72 		36
33 		25  TP53m: 25.5
(BA: 13, MA: 29.2)
TP53 WT: 33.7 
VIALE A trial18-20
phase 3, randomized
Azacitidine + venetoclax [E] 		AML ineligible for intensive chemo 431, 52
286, 38 		76 40 66d, 55  Overall: 14.7, 5.17e 
Azacitidine [C]  145, 14 76 40 28, 0  Overall: 9.6, 4.9 
Phase 1b27
Magrolimab + azacitidine 		Untreated AML ineligible for IC 87, 72 73 43 32, 32 61 Overall: 10.8;
TP53m: 9.8 
Phase 1b
Magrolimab + azacitidine28  		Untreated MDS 95, 25 69 35 33, 40 41 Overall: NR;
TP53m: 16.33 
Phase 1b/2
Eprenetapopt + azacitidine (2)33  		HMA naïve— TP53-mutated high-risk oligoblastic AML, MDS/AML, MDS and MDS/MPN, CMML 55 66 53 44f 21 10.8 (95% CI, 8.1 to 13.4) 
Phase 2
Eprenetapopt + azacitidine34  		HMA-naïve TP53-mutated AML, MDS/AML, CMML 52 74 48 57: MDS
36: AML 		23 12.1 (MDS)
10.4 (AML) 
Phase 135
Eprenetapopt + venetoclax + azacitidine [E] 		MDS previously transplanted or treated with HMA
Untreated TP53-mutated AML 		49 (40 BA)
43 		67 47 38 41 7.3 (95%
CI 5 · 6-9 · 8) 
Eprenetapopt + azacitidine [C] 6 69 67 17   
Phase 1b38
Cohort A: tagraxofusp + AZA (MDS)
Cohort B: tagraxofusp + AZA + ven (AML) 1L and RR
Tagraxofusp + AZA + ven (AML) 1L only 		New and R/R AML CD123 positive (declined/ ineligible for IC)
HR-MDS for cohort A 		82
19
37
26, 13 (multi-hit TP53 m-9) 		62
70
71 		37
41
39 		(69, 54)g  Overall: 14; TP53m: 9.5 
MBG45341
Phase 1b
Sabatolimab + HMA (decitabine or azacitidine) 		Untreated HR/VHR MDS or CMML 68, 14 70 (MDS)
68 (CMML) 		45 (MDS)
20
(CMML) 		20, 29  Overall: 26.7 
STIMULUS-MDS 1
Phase 2
Sabatolimab + HMA [E] 		Untreated intermediate/high/very HR-MDS 127, 41
65, 22 		73 37 23  Overall: 19 
HMA alone [C] 62, 19 73 27 21  Overall: 18 
Phase 142,44
SL-172154 (19)
SL-172154 + azacitidine (18) 		R/R AML or MDS
TP53m-MDS (for SL-AZA) 		37, 14
19
18 		70 38 1 CR and 1 marrow
CR in TP53m 		  
a

In some of the studies, all patients may not have undergone evaluation for TP53 mutation.

From among TP53-mutated patients, many studies do not report on allelic status of the TP53 mutation.

b

CR rates of the evaluable participants from the studies referenced. Reported CR could be best response, or response after a certain number of cycles.

c

Trial was designed to include AML 20% to 30% blasts patients; however, only CMML and MDS data are reported.

d

In this study, the reported values are composite CR, which includes CR and CRi; MRD positivity is a percentage of CR/CRi.

e

The study referenced reported cumulative median OS for TP53-mutated and poor-risk cytogenetics patients from VIALE-A trial and a phase 1b study with venetoclax and azacitidine.

f

47% are NGS negative CR from among the total evaluable 45 cases.

g

Includes CR/CRi or MLFS.

h

A study comparing oral ASTX727 (cedazuridine/decitabine) to IV decitabine.

AZA, azacitidine; BA, biallelic; CR, complete response; CRi, complete response with incomplete count recovery; dec, Decitabine; MA, monoallelic; MLFS, morphological leukemia free state; NA, not applicable; NR, not reached; 1R, first line; RR, relapsed refractory; TP53m, TP53 mutated; VAF, variant allele frequency; ven, venetoclax.

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