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Talha Badar: Transplant or not to transplant for TP53m AML

Photo taken from Talha Badar/Twitter

Mar 27, 2024, 13:57

Talha Badar: Transplant or not to transplant for TP53m AML

Talha Badar, Hematologist/Oncologist at Mayo Clinic in Jacksonville, Florida, shared a post on X/Twitter:

“Weekend review

Transplant or not to transplant for TP53m AML:
Potential factors that can potentially impact outcome: co-occurring mutations, complex CG, mutation type missense vs truncating, depth of remission, conditioning intensity, post transplant strategy.

Induction intensity:
Induction intensity has not really shown to impact depth of response, in our RWD, Ven plus HMA had a better odds ratio to achieve CR compared to intensive chemotherapy. In MVA HCT only factor to improve outcome. Magrolimab and APR-246 in spite of early promising results, failed to show benefit. Optimal induction regimen still to be explored!/the article/

Impact of TP53 allelic state and outcome in AML:
We and other have reported no significant impact of allelic state and outcome in TP53m AML/the article/

Conditioning intensity and outcome in TP53m AML:
CIBMTR study, 289 pts with TP53m MDS (median OS, 7.5 months vs 9.2 months, respectively; P = .19).
EBMT study; no significant difference between RIC vs MAC in 179 pts with TP53m AML. doi:10.1002/cncr.34268
FluBu2 with Ven conditioning; P1b study on 22 pts, 12 were TP53m, @ 14 mo fu 50% alive.

Post HCT maintenance:
PIII study of AZA, did not show benefit to improve outcome.
Eprenetapopt (APR-246) with AZA, Planned analysis on 33 pts for 12 cycles, 39% completed, median cycles given were 7; 1-year OS of 79% after a median follow-up of 17 mo

Allogeneic Immunotherapy:
Preemptive DLI to enhance GVL effect with low dose HMA in HR MDS/AML has been evaluated with 2yrs OS ~ 65.5%. Study not specifically evaluated TP53m pts.

Talha Badar: Transplant or not to transplant for TP53m AML

We conducted RWD study under COMMAND consortium to look at predictors of outcome with HCT in 370 pts.
EFS 12.4 mo (95% CI: 6.24-18.55), OS was 24.5 mo (95% CI: 21.80-27.25). Conditioning intensity or maintenance didn’t suggest to impact outcome. D100 CR and occurrence of cGVHD impacted outcome.

Talha Badar: Transplant or not to transplant for TP53m AML

Systemic review and meta analysis suggest alloHCT improve OS in TP53m AML; 3 yrs PFS 32.5%, 2 yr OS 29.7 mo

Conclusion:
While HCT should not be denied for eligible pts with TP53 mutation, better pre-transplant and post-transplant strategies are warranted to improve outcome!”

Source: Talha Badar/X