Tag Archive for: Olutasidenib

Olutasidenib for Relapsed or Refractory Acute Myeloid Leukemia with IDH1 Mutation


Once again a new drug that was recently FDA approved for some Acute Myeloid Leukemia (AML) patients. Olutasidenib (brand name: Rezlidhia) was approved in December 2022 for AML patients who have relapsed or are refractory to treatment (R/R) with a mutation in the Isocitrate Dehydrogenase 1 (IDH1) gene. There is a different gene called IDH2, which can also be mutated in patients with AML, but different medications are used for IDH2 mutations. 

An existing drug, called ivosidenib (brand name: Tibsovo) was already approved for patients with AML and a mutation in IDH1. It was initially approved in July 2018 as a single agent for patients with R? AML with a IDH1 mutation. Later it was approved for use in combination with azacytidine for newly diagnosed AML patients with an IDH1 mutation. There was also a specific test (the Abbott RealTime IDH1 Assay) approved along with the initial approval of ivosidenib. This test was also approved to select patients to be treated with olutasicdenib.

Results of the Current Study 

The study used to support the approval was a non-randomized trial (all patients received olutasidenib). The study included patients with AML and ones with Myelodysplastic Syndrome (MDS) who had a mutation in the IDH1 gene. Patients were treated with olutasidenib as a single agent (monotherapy) as well as combined with azacytidine. The approval was based on the results of the 147 patients who received olutasidenib monotherapy (the results are described in detail here). 

In the study, about 35% of patients achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) – the latter means that they appear to be in remission, but their blood counts are not normal. In addition, about one third of patients who were platelet and/or red blood transfusion dependent at the start of the trial eventually did not require transfusions for 8 or more consecutive weeks (transfusion independent). All patients experienced 1 or more adverse events (AEs) and almost all experience a serious (Grade III or IV) AE. These AEs are expected in patients with AML, particularly older patients, as most of the patients were. 

Comparison with Ivosidenib 

Now that there are 2 drugs approved for AML patients with an IDH1 mutation, the question becomes which drug should be used and in which circumstances. There have been no studies (at least ones that are published) that directly compare the drugs. According to the paper from Bload Advances on the responses to olutasidenib and ivosidenib as single agents was about the same, however the length of remission in the patients receiving olutasidenib (a median of 25.9 months) compared to ivosidenib (8.2 months0. The big caveat is that, since the comparison was not randomized, it is difficult to determine if there were differences in risks in each group. My guess is that there will not be a randomized comparison of these two groups.

It will be more interesting to look at these drugs in combination with azacytadine and also as a 3 drug combination of azacytidine and venetoclax. In addition, these drugs could be combined with existing intensive chemotherapy regimens (for instance, so-called 7+3 induction with cytarabine and daunorubicin). Likely the combinations would produce more remissions but might have significantly more side effects. 

In summary, the good news is that there is another drug that can help some patients with AML, the bad news is that the determination of the best therapy is yet more complicated. 

Further reading 



Advances in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (AML)

Advances in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (AML) from Patient Empowerment Network on Vimeo.

AML expert Dr. Omer Jamy discusses his approach when considering treatment for patients with relapsed or refractory AML, including transplant eligibility, molecular markers, and whether clinical trials may be an appropriate option.

Dr. Omer Jamy is a Leukemia and Bone Marrow Transplant Physician and Assistant Professor at the University of Alabama at Birmingham. Learn more about Dr. Omer Jamy.

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What Is the AGILE Study? Research for AML Patients With the IDH1 Mutation

What Is the AGILE Study? Research for AML Patients With the IDH1 Mutation

What Is the Purpose of AML Genetic Testing

What is the Purpose of AML Genetic Testing?

Essential Testing | Optimizing AML Care With Personalized Medicine

Essential Testing Optimizing AML Care with Personalized Medicine


Katherine Banwell:

Dr. Jamy, are there any recent advances that may affect the care of patients with relapsed or refractory AML? 

Dr. Omer Jamy:

Yeah, that’s a good question. So, patients with relapse refractory AML, of course, carry a poor prognosis. That means that chemotherapy was working and has stopped working or chemotherapy didn’t work from the get-go, right?  

So, in my practice I try to divide patients into two different buckets. One is that I need to get them into remission, and they’re fit for a transplant, so I take them to transplant.  

So, then my treatment approach is a little different for those patients. As opposed to someone who’s elderly or too frail, that they may go into remission, but they may not be able to proceed to stem cell transplantation after that.  

So, what happened in the relapsed/refractory setting also depends on what the patient received in the upfront setting. Ideally, I would recommend a clinical trial enrollment for patients with relapse refractory AML if they have access to it. At the time of relapsed/refractory AML, it is very important to again profile the leukemia to see if there are any mutations that were present at diagnosis or if there are any new mutations for which there may be targeted therapy. Some of those mutations for which we have targeted therapy include FLT3-ITD for which there is a drug called gilteritnib (Xospata), which is FDA-approved in the relapsed/refractory setting. 

We spoke about IDH 1 which is ivosidenib, IDH 2 which is enasidenib (Idhifa) is also approved for patients with relapsed/refractory AML. And then more recently the FDA approved another IDH1 compound called olutasidenib (Rezlidhia) which is also for patients with relapse refractory acute myeloid leukemia with an IDH1 mutation. I think these are target therapies which have shown to get people into a second remission and beyond. And these have been approved in the last few years. And I think it is very important to basically test whether the person harbors these mutations so that we can target them accordingly.  

For patients who don’t have any mutations we would generally, outside of a clinical trial, probably use the combination of some of the approved agents that may be venetoclax (Venclexta) with azacitidine (Vidaza) or decitabine (Dacogen). Patients who may have received this venetoclax or a hypomethylating agents frontline and may still be eligible for intensive chemotherapy.  

You could offer them intensive chemotherapy in the relapsed/refractory setting, but I would say that at this point being at a center where there’s opportunities to enroll in a clinical trial would be really helpful as well.