Methods of stratifying patients for treatment with retinoic acid receptor-alpha agonists
AssigneeSyros Pharmaceuticals, Inc.
InventorsMichael Robert McKeown, Christopher Fiore, Matthew Lucas Eaton, Emily Payton Lee, Christian Fritz
Life of this patent
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Abstract
Described herein are methods that define cellular populations that are sensitive to RARA agonists and identify patient populations that will benefit from treatment with RARA agonists. The methods may comprise administering RARA agonists to patient populations.
Claims27
A method of treating a disease or condition selected from the group consisting of non-acute promyelocytic leukemia acute myelogenous leukemia (non-APL AML) and myelodysplastic syndrome (MDS) in a subject, the method comprising a step of:
- administering effective amounts of tamibarotene and azacitidine in combination to the subject, wherein, prior to administration, a PBMC sample or an enriched PBMC sample from the subject has been determined to have at least one of:
- (i) an elevated RARA mRNA level relative to a threshold level determined by RARA mRNA levels observed in comparable samples from a population of subjects having the same disease or condition as the subject, wherein the RARA mRNA is transcribed from a RARA gene that encodes a functional retinoic acid receptor-α and specifically excludes gene fusions that comprise all or a portion of the RARA gene;
- or
- (ii) an elevated IRF8 mRNA level relative to a threshold level determined by IRF8 mRNA levels observed in comparable samples from a population of subjects having the same disease or condition as the subject.
A method of treating a disease or condition selected from the group consisting of non-acute promyelocytic leukemia acute myelogenous leukemia (non-APL AML) and myelodysplastic syndrome (MDS) in a subject, the method comprising a step of:
- administering an effective amount of tamibarotene to a subject that is
- (i) suffering from non-APL AML or MDS;
- and
- (ii) receiving azacitidine;
- wherein, prior to administration of the tamibarotene, a PBMC sample or an enriched PBMC sample from the subject has been determined to have at least one of:
- (a) an elevated RARA mRNA level relative to a threshold level determined by RARA mRNA levels observed in comparable samples from a population of subjects having the same disease or condition as the subject, wherein the RARA mRNA is transcribed from a RARA gene that encodes a functional retinoic acid receptor-α and specifically excludes gene fusions that comprise all or a portion of the RARA gene;
- or
- (b) an elevated IRF8 mRNA level relative to a threshold level determined by IRF8 mRNA levels observed in comparable samples from a population of subjects having the same disease or condition as the subject.
A method of treating a disease or condition selected from the group consisting of non-acute promyelocytic leukemia acute myelogenous leukemia (non-APL AML) and myelodysplastic syndrome (MDS) in a subject, the method comprising a step of:
- administering an effective amount of azacitidine to a subject that is
- (i) suffering from non-APL AML or MDS;
- and
- (ii) receiving tamibarotene;
- wherein, prior to receiving tamibarotene, a PBMC sample or an enriched PBMC sample from the subject has been determined to have at least one of:
- (a) an elevated RARA mRNA level relative to a threshold level determined by RARA mRNA levels observed in comparable samples from a population of subjects having the same disease or condition as the subject, wherein the RARA mRNA is transcribed from a RARA gene that encodes a functional retinoic acid receptor-α and specifically excludes gene fusions that comprise all or a portion of the RARA gene;
- or
- (b) an elevated IRF8 mRNA level relative to a threshold level determined by IRF8 mRNA levels observed in comparable samples from a population of subjects having the same disease or condition as the subject.
Dependencies are inferred from the claim text.