Experimental compound for myelodysplastic syndrome shows potential in phase III trial

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.