Tag Archive for: Magrolimab

Emerging AML Treatment Classes Showing Promise

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Emerging AML Treatment Classes Showing Promise from Patient Empowerment Network on Vimeo.

What therapies are in development for acute myeloid leukemia (AML)? Dr. Ann-Kathrin Eisfeld discusses the latest research for AML treatment, including menin inhibitors and CAR T-cell therapy.

Dr. Ann-Kathrin Eisfeld is Director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University and a member of the Leukemia Research Program at the OSUCCC – James. Learn more about Dr. Eisfeld.

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Transcript:

Katherine Banwell:

Are there therapies in development that are showing promise for patients with AML? 

Dr. Eisfeld:

There are so many of those. It’s hard to count. And this makes me very happy. There are exciting and again, targeted drugs.  

Once drug class is called menin inhibitors, which we – which were just published that show high promise.  

And again, very difficult to treat several groups of patients who harbor chromosome changes in MLL genes in here. So, that is a very exciting option.  

And there’s very exciting treatments with respect to what you call antibodies – monoclonal antibodies that attacks the surface proteins that are being checked regularly. And one of those, for example, is called magrolimab. And that has even promise in these high-risk leukemias or adverse risk leukemias.  

And then we are not there yet, but I’m sure we will be in the not too near future. There are also multiple trials that are looking at what we call CAR-T cells. But patients might have heard about for lymphomas or acute lymphoblastic leukemias. AML is a little more tricky with respect to those. 

But we’ve seen pre-clinical studies that look really exciting. And I think it’s just going to be just a little more fine-tuning to make those easier, available, and more targeted for AML patients. And I’m very much looking forward to seeing those come more onto the market.     

Katherine Banwell:

You mentioned the new menin inhibitors. Who are they right for?  

Dr. Eisfeld:

We try to find out more, but definitely for patients that have been shown to be beneficial for patients who have chromosomal and rearrangements of the MLL gene or KMT2A gene. And there’s also good data on patients who have NPM1 mutations.  

Even though we know – and these are mutations who harbor this kind of genetic change – have now a plethora, which is a great, of treatment options. 

Because we know even conventional chemotherapy has been working decently well in them. We know that venetoclax also is supposed to work very well in them. But again, the data on the menin inhibitor with respect to NPM1 mutations is very exciting. 

Challenges in Treating TP53-Mutated AML, Hope on the Horizon

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Challenges in Treating TP53-Mutated AML, Hope on the Horizon from Patient Empowerment Network on Vimeo.

TP53-mutated acute myeloid leukemia (AML) treatment has some challenges. Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares his perspective. Learn about promising treatments on the horizon for this AML subgroup. 

[ACT]IVATION TIP from Dr. Daver: “The TP53 mutation remains the most difficult subset of acute myeloid leukemia, there is hope on the horizon with new treatments such as CD47 antibodies and targeted therapies like APR that are being looked at, and also a strong consideration for allogeneic transplant in TP53, because this seems to be the only modality associated with a good chance of cure after achieving remission with one of the frontline therapies.”

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 Why Is the Menin Pathway Important in AML

Why Is the Menin Pathway Important in AML?

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What Is MRD-Positive Acute Myeloid Leukemia?

Transcript: 

Art:

Dr. Daver, what have we learned about TP53-mutated AML? And what is the takeaway for these patients?

Dr. Naval Daver:

TP53-mutated AML remains the most difficult molecular subset of all acute myeloid leukemia. Patients who have this mutation, unfortunately, do not respond well to any of the established standard care therapies, including intensive chemotherapy, the HMA alone, such as azacitidine (Onureg or Vidaza), decitabine (Dacogen) alone, or even HMA venetoclax (Venclexta) with all of these, we do see responses, especially with HMA venetoclax or intensive chemotherapy, we can see 15 to 55 percent remission rate, but the remission, very short lived, early relapses and the median overall survival across all of these currently available standards of cares are between six to 10 months.

So there has been an intense effort in the last six, seven years to develop TP53-directed therapies or therapies that will work regardless of TP53 mutation, and there are two drugs this time that are very promising and being evaluated as ongoing Phase II and Phase III studies.

One of them is an immunotherapy drug called magrolimab which seems to have very similar activity and probability with good response rates in TP53-mutated AML. This has been completed in a single arm phase 1B study in front line TP53-mutated AML where we saw close to 50 percent CR, CRI complete permission rates. And median survival was above 11 months in older unfit TP53, which is better than any survival we have seen in the past in this population.

The other study was with the oral care targeted therapy towards TP53, called APR, and this therapy was specifically designed to target the TP53 mutation, and this is being evaluated in the frontline setting in combination with a society in venetoclax. We hope that these regimens are these novel therapies, one or both of them will be able to at least incrementally improve their current outcomes in TP53.

The other area where we have really been doing a lot of research, and I think the data is suggesting, is that allogeneic transplant may work for separate, and we are routinely considering transplant in these patients in the frontline setting, once they are able to achieve remission.

My activation tip is the TP53 mutation remains the most difficult subset of acute myeloid leukemia, there is hope on the horizon with new treatments such as CD47 antibodies and targeted therapies like APR that are being looked at, and also a strong consideration for allogeneic transplant in TP53, because this seems to be the only modality associated with a good chance of cure after achieving remission with one of the frontline therapies. 

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A Look at Ongoing Acute Myeloid Leukemia Phase III Trials

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A Look at Ongoing Acute Myeloid Leukemia Phase III Trials from Patient Empowerment Network on Vimeo.

What are the acute myeloid leukemia (AML) Phase III clinical trials that are ongoing? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares his perspective about encouraging trials. Learn about the MORPHO Study and others. 

[ACT]IVATION TIP from Dr. Daver: “The maintenance with gilteritinib and the MORPHO Study, as well as the relapsed refractory study as well as the use of a e-selectin inhibitor called uproleselan, and hopefully this will lead to approval of the next batch of three or four drugs, which will further improve outcomes for frontline as well as relapsed AML.”

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Transcript: 

Art:

Dr. Daver, can you speak to some of the ongoing Phase III trials in AML, what are you most excited about?

Dr. Naval Daver:

This time there are numerous ongoing phase three in acute myeloid leukemia, some in the frontline, some in the relapse setting. In the frontline setting, the ones that I’m most excited about are trials incorporating a novel immunotherapeutic pathway called the CD47 antibody that works to activation of macrophages, these are looking at a very high-risk molecular group of acute myeloid leukemia, the TP53 in adverse cytogenetics, and there are two randomized phase threes with this agent, one focused on TP53 mutated AML looking at the azacitidine and magrolimab versus the current standard of care FDA-approved azacitidine-venetoclax (Onureg or Vidaza-Venclexta) in TP53 mutated. 

The other is actually looking at all older unfit AML so trying to improve on azacitidine venetoclax doublet with a triplet, so this is looking at azacitidine venetoclax magrolimab versus azacitidine-venetoclax placebo so if both of these trials are positive, then this will lead to incorporation of immunotherapy in the frontline setting in AML, which is exciting and something we’ve been working towards for the last 10, 15 years.

The other Phase III trials in the frontline setting or in the maintenance setting really that I’m excited about is called the MORPHO Study…this is using a FLT3 inhibitor gilteritinib (Xospata) as a maintenance post-transplant, so we know FLT3-mutated patients respond well, when they receive intensive induction FLT3 inhibitor, we still need to take them to transplant because even though the initial response is good, many can relapse. 

So we actually try to give to the cycles of intensive induction for the move to transplant, and then if we start there, we still see at about 40 percent of these patients can relapse in the next three years, so this has led to efforts to add a maintenance FLT3 inhibitor gilteritinib single agent post-transplant as a maintenance for one to two years versus placebo observation, which has historically been a standard of care, and so this is being looked at a large multi-center called the MORPHO Study that we hope to get data from in the near future.

Another study in the similar design that’s being done by the UK cooperative group is looking at maintenance with the oral azacitidine, post-transplant for non-FLT3, so similarly, can we overall improved outcomes not just for FLT3, but the general patient population is going to transplant by using the maintenance oral azacitidine post-transplant versus placebo.

And in the relapse setting, there is a very novel unique oral therapy drug called uproleselan, which is an e-selectin inhibitor, and this agent is now being combined with traditional salvaged chemotherapy such as FLAG-Ida mec versus the placebo mec plus FLAG-Ida or mec in the relapse setting.

And that’s what he’s actually been completed to enrollment, and we’re hoping to hear data from that in the near future. So these are the major randomized studies focusing on TP53, FLT3, and relapsed refractory AML  that we’re looking for in the near future and hopefully could lead to two or three more new approvals in the AML space.

My activation tip for this question is that there are ongoing numerous frontline Phase III as well as relapsed refractory Phase III, targeted immunotherapy approaches, specifically among these we’re excited about the CD47 antibodies. The maintenance with gilteritinib and the MORPHO Study, as well as the relapsed refractory study as well as the use of a e-selectin inhibitor called uproleselan, and hopefully this will lead to approval of the next batch of three or four drugs, which will further improve outcomes for frontline as well as relapsed AML. 

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A Look at Treatment Strategies for High-Risk AML Patients

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A Look at Treatment Strategies for High-Risk AML Patients from Patient Empowerment Network on Vimeo.

What acute myeloid leukemia (AML) treatments are available for high-risk patients? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses various mutations, potential for cure, and clinical trials. Learn about the outlook for high-risk AML treatments.

[ACT]IVATION TIP from Dr. Daver: “The best way to get up to these agents is to go on clinical trials and incorporate these therapies, both in the frontline setting as well as in the relapsed refractory setting.” 

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 Assessing Untreated AML Patients Who Are Ineligible for Intensive Chemotherapy

Assessing Untreated AML Patients Who Are Ineligible for Intensive Chemotherapy

What Does Triplet Therapy in AML Mean for the Future (2)

What Does Triplet Therapy in AML Mean for the Future?

Transcript: 

Art:

Dr. Daver, what treatment strategies are available for high-risk AML patients?

Dr. Naval Daver:

High-risk AML patients includes a group of a number of different mutations, and cytogenetic abnormalities, this includes TP53 mutation, as well as adverse cytogenetics, which includes chromosome 17, deletion 5, deletion 7, as well as complex carrier type. This entire group historically had a poor outcome and has had limited responses to traditional intensive chemo, even if we achieve responses there, usually short-lived.

We do have some patients where we are able to achieve remission with intensive chemo or with azacitidine-venetoclax (Vidaza-Venclexta) and transition and transmission them transplant with about 25 to 30 percent potentially achieving a long-term remission and possible cure. 

But aside from that, there is very little potential to cure these patients with just traditional intensive chemo, venetoclax in this area, there has been developments with the emergence new class of immunotherapy drugs, called CD47 antibodies, the one that’s most advanced in this field is a drug called magrolimab, and we are evaluating the drugs such as magrolimab in combination with azacitidine as well as in combination with azacitidine-venetoclax and are seeing high remission rates, both in TP53 mutated and TP53 wild type.

So this pathway that works by activating a macrophages or the immune system to attack the tumor cells, seems to be in some way mutation agnostic with response rates being maintained even in the traditional high-risk subsets, especially such as TP53 and complex cytogenetics for some of the other high-risk groups such as MLL, we’re using targeted therapies like menin inhibitors, and these seem to work well in those patients who have these adverse cytogenetic molecular abnormalities, so there is progress, and we think that the CD47 antibody field and hopefully the main inhibitor feed will be able to improve outcomes in these traditionally molecular cytogenetic subsets.

My activation point related to this question is for high-risk mutations and cytogenetic commonalities such as TP53 complex carrier chromosome 17 MLL,  best hope at this time is in clinical trials evaluating novel therapies such as CD47 antibodies and menin inhibitors. These are not yet FDA-approved, but based on emerging data from the ongoing Phase I, II studies, we think that there is a good chance they will be approved in the future.

However, this time, the best way to get up to these agents is to go on clinical trials and incorporate these therapies, both in the frontline setting as well as in the relapsed refractory setting. 

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