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of currently the before Anderson years I XX MD as in As of the for mentioned, I Leukemia, am training plus the the my Georgia and Deputy faculty Chair, and there Department Director formerly Cancer Center where on was that.
discuss role in So and leukemia. the I'll patients acute you with IDHX to drug myeloid glad this of be mutated very olutasidenib with
Slide background start with I'll XX. on So the
X% a X% to As And the from this on to a patients see reminder, IDHX occur where bit mutations can sources type patient of more acute populations, around about range of in mutation. may see depending different XX% you leukemia, different somewhere that's expand little myeloid XX%. with we somewhere and to
cells have through it into two I are biochemistry, that hydroxyglutarate already think in it normal it's normally Normally, may and and normal the is inhibitor usually bit Krebs alpha-ketoglutarate those. developed that work that IDH, hematopoietic olutasidenib When leukemia potential metabolism epigenetic mutations are alpha-ketoglutarate acute normal mutations. you and happen of mutations leukemia root all the XHG which mutations, or a mutations remember, the goes cells, from it has transforms cycle. important little in has of myeloid cells. - to is that cycle, IDHX some cells after a XHG that are as this of development alpha-ketoglutarate, into to present this very it that been the l it And the into metabolizes formed, the is mutated, transform later when is to we which considered As is you one the metabolite will those not cells, mentioned, from some and when cells leukemia. we when leukemia in mutations mechanisms. one of initiating because very because of and That's very important remind IDHX select myeloid leukemia, of There IDHX initiating are acute important mutated. And is how goes
mutation, biomarker the IDHX. levels development the will XHG if go again, will thing the of a a marker, you up is And there a of when the actually becomes So a what drives of is of is IT down, because, which go leukemia. mutation ADHX, good that XHG inhibit
very So olutasidenib, phenotype. IDHX available, for can it being reverse a malignant drug active important, selective having that very
the we with of So getting have a the with as beginning, of olutasidenib, both drug from development as started slide of this you And combination agent, need a a I quickly sometimes and this the the being - that see other comprehensive very stages in agents, development. the when very the single you certain involved we a for in plan for combination developed from understanding of can very potential monotherapy knowing with settings. leukemia XX, very that started on early drug I
So the relapse we the also therapy. other orange in monotherapy refractory, And the combination explore are who includes patients not have patients, therapy, settings, including boxes. the treatment-naive prior of exploration those received that and some
purposes indication most the presentation, the the this see mature drug. that's is primary XX, of for monotherapy is is relapse the is we usually to which of again, in the most that that be start development is a the going would data the moment, patients, you'll that's pursued Slide Now where data of at refractory what because where
duration So what primary get for CR the the definitions of achievement a this or cohort, overall but of the that I'll the transfusion the of of of of we there survival And safety independence, and, remission, the is essentially rate, drug. CRH, end minutes. the to a called was endpoint a in the course, secondary points, the is important overall the responses, couple the have response
you this the for results. is call mostly thirds opposed syndrome is presented about evaluable meaning describe in So on characteristics can Two Slide from the are the These frequently, cohort could what see XXs, their included XX. included the now. patients. neoplasms happens novel those patients, but are to hematologic the can a first time, have that's of AML third up younger be the patients the other let that we these malignancies, disease and The end of which from age but being of that evolves you see of the XX, as are a patient patients And secondary in me myelodysplastic AML, study. as other that some upper the spectrum, AML, sort at we an into a it patients, this do is myeloproliferative is median way older that We most neoplasia, had typical a AML. a these developed had had cancers, the in lymphoma, cancer, patient populations. treatment-related you over chemotherapy, others had were mutation, Those there's It's abnormalities an AML abnormality. different patients of just definition, extra see chromosome RXXXC, that's no of patients little risk the few The of - that slide. poor little are happens half breast over intermediate Those frequently X. XX% a other all patients common that we and But a a chromosomal the or in them most abnormalities, the variations mutation have the and you some have risk that on patients chromosomal others and represents good et is very mutation. chromosomal most either a the majority cetera, that this IDHX then the By that of this IDHX give that what call they few. it
in them slide. XX% on or cohort, We with They That patient that but others, have mutations. genes over refractory we and that most about respond did The a do largest patients, you means, patients. We're other mutation, that it's BX all. see myeloid saw could initial XX% little genes the occurred also almost the you always saw the frequent Refractory other this mutations and relapsed is therapy. of IDHX coexist gave not only the can acute at in mutations know as talking of population. in NPMX one was with cohorts leukemia patients we these not in
you again, means is have disease the and the is you scenario cohort, responded others disease before they but patients also patients therapy, The risk, had the quickly have to response months. give responded, prognosis. the that is The could they XX%. relapse, that largest that a the either tend the And some initial something That worst give relapsed is comes There back be them coming else, them that back. are again. XX worst-case relapsed. highest That next
of also the That’s remission that’s the the So two a case this more of in pretty, or are relapse more and than patients XX% the And XX first of cohort first lasted a months. like XX% patients that. scenario patients, these the smaller is subset who bad patients. only best relapses have
of regimens prior two. the patients median You can had see actually, number the of received, that was most
before CR XX% received they primary response at see two rate endpoint a jump is on mentioned So least actually many had And came therapies here plus transplant. had was they studies, some prior can then. to XX. received as CRH. stem This let's the you Slide cell received All and had right, the the I seven, to that as
blast of [ph], the CR Let that that for those more less cells, may me is the X%, or leukemia be blast define leukemia. familiar. be normal than counters you not essentially than the who that the as the would means
means of and neutrophils completely, more not not XXX,XXX. more And is but but CR but there and the at below to that are If the recovered CR. than to than not So recovery quite XXX,XXX the some the platelets, have blast gone least least XX,XXX, platelet quite platelets count X,XXX. than X,XXX. a X%, That's than down at more the more the is the has XXX, and so neutrophils neutrophils
blast a CRH. the that's than still With X%, less
here that endpoint. primary see can XX% patients you that So achieved the of
full Importantly, are majority CR, the the these great XX%. of
of good, are the four who is responded CRh CRh. XX but response. only are the CR certainly So patients - ultimate is
did categories, And to or the smaller recovery really not down blast there's the in X%. means neutrophils. this And of call not the those count down We but response. to less some MLFS, the XXX the than went the means the went make go that X%, CRh. that leukemia the patients a way ratios, neutrophils not and then PR XX% less it to freestate, platelets, XX some We count platelets of than recovery the those There's also morphologic much do have have they it of an of to the blast down, patients who all CRIs. but but additional couple the quite have and -
with somebody say, Let's started and to it blast, went XX% down X%.
response, that's full a X%. to it partial make less the While than quite doesn't criteria of
of almost you the categories very least these the of of the had duration patients of half see on responded, what together, XX% one is you take all of Slide response. response. patients of But If at XX these importantly,
see want for last relapses. these happen not the responses then patient that time some time, to You and just one immediately
As called here, end you duration response duration these the the the analysis is response see and to of has this a well, say, what's is approach, you time to been not went patients can reached. of sensitivity the analysis, some a the because I'm time to transplant. if median At conservative at went of yet - do the a transplant. going they very
So then to outstanding good adjudicate mentioned primary alive, transplant. very that this median something had. the that went survival and patients outcome. of reached, a is We a months, duration that the then counting been they And just that still CRh, CR something drug the according are point. XX.X, also important. an to not And survival and to or again, it's of response the XX% CRh the a has they XX The the the median to partially which yet is shows attributed patients a by still the stopped was who endpoint the outcome. had relapsed patients was transplant, not I Slide on very because at very, I don't that XX, they CR
mentioned, had median also morphologic very that median benefit. survival of have these they months. CRIs, importantly, a lesser leukemia-X, the months a responses a did I who not respond, the of more four year the XX of These compared only survival or a than have Now patients to some patients who survival
responses to four median. the value means add significantly lesser survival to patients, months that from So probability XX the even the as that to have the months
events, patient olutasidenib. report are now here that the treatment happened, adverse happens called related drug, a related. bit it. happens is safety showing little we of you TEAE the was anything it and is any the talk say not I while the patient while assumptions - is am toxicity means what what We that making about emergent taking is just or that that we it Let's not
with XX% the these that of typical happened X go more neutrophils that in patients or So severe the down, When goes treatment Grade that the X, more patients XX%, or adverse at you was down, any least events. their in with a Grade platelets anything X leukemia, or X down. it's instances go or treat of hemoglobin very
of So that anemia, any a it's X patients. of grade neutropenia. is - a a of reached It's in XX% the than to only a quarter X. those, Well, ones are or patients, it or that in of And the on X. any things. these chemotherapy great course, here constipation of their X slide. in nausea Grade this little fairly fatigue are third of stand drop have thrombocytopenia, adverse neutrophils of standard the But some of these significance actually, see the very that's the frequently some have XXX% ones any patients, you of make in that the well. out patients that other majority events none reported really with only it's as And [ph] Grade fever the those over Grade terms who But the patients
So these you would example. than for were clearly mild these effects much for better side that maybe chemotherapy, with a patients, expect manageable what
to Slide the to special moving events interest want of are adverse of particularly XX. point important. I Now things on some that of some
an QT graphics an electrocardiogram. seen electrocardiogram, the interval First, is those you've the QTc With of prolongation. in QTc,
that's from one measure wave wave that's wave. the wave the You other Q and called called the T
we gets is risk and of long, very even fatal between very see If You there those. can see [indiscernible] be the it interval that that sometimes.
the patients and very lead any happened the it patient it prolongation. here, importantly, infrequently, X, the did only even of But QTc X happened most the that long intervals, most was about, fortunately Grade to the less ones one Grade had XX% not very drug. worry discontinuation But in we the of Now X. that than and Grade
This abnormality. very perhaps low have it events saw were was we frequently. that adverse and rate blood very more other So the manageable. than a liver Then we counts the
between grade You with anywhere XX% for happened see bilirubin the transaminases XX% any to AST. of in one
were percentage of Fortunately, patients. in these X a Grade small
XX modification XX% continue any seven overall, elevation Grade of those was XX of XX patients, or But of Grade on patient importantly, discontinued enzymes, these most or X, the X. not treatment. XX% actually of if require had liver dose dose any were therapy. they of had to for There with modification are a patients very So have these but Grade only only enough X patients did that
For with did to recurrence, with investigator or want not anything. adjustments re-challenge three dose others
So Grade use know meaning hydroxyurea or have of Grade were X, Grade happened know syndrome, would of the these with are of that X, syndrome interruptions. that of inhibitors, others managed happen. - these majority it and X were there. process only fortunately, half Grade And can symptoms on differentiation happened a. X great well very total, We of patients of we and is of it is IDH about come - then XX% problems part differentiation only with the But something learned can happens corticosteroids but or maturation, like we've what with most don't be patients, the because treatment treatment mild that some discontinued chemotherapy drugs the these X% however, they three of with a
toxicity and the very a of intensity very, low rate low the these manageable events. So because of
also do that CR leukemia. benefit. CRh are very mutation, drug have the of all And this heavily extends patients IDHX very accounting of that a for very have with they the full patients not responses, even rate, well makes a survival or a with population. that toxicities with interim very very pretreated durable drug applicable, are these in management comes olutasidenib these these year they're median and high conservative transplant more of duration very that remissions of that is very this see is manageable, the we mild most a for analysis this analysis, importantly, high the with rates but And these oral, that true CRs, most benefit than CR/CRh, even that myeloid a a conclusion with response that's welcome very very my with and tolerated, very So has that's it acute patient
to and I is I'll it you this hand my presentation. for speaker. thank attention, your So next our over
