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Antibodies, Immunotherapy and Clinical Trials

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Published on February 26, 2020

Key Takeaways

  • There has been a significant increase in treatment options for ALL in the past five years.
  • Blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa) and chimeric antigen receptor (CAR) T cells were recently approved for relapsed and refractory ALL.
  • Participating in a clinical trial may give you access to the latest treatments options.

“There’s been a big expansion of treatment options for ALL—it’s no longer just chemotherapy,” says Dr. Shira Dinner, an acute lymphoblastic leukemia expert from the Feinberg School of Medicine at Northwestern University. Dr. Dinner met with Patient Power Co-Founder Esther Schorr at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition to share the latest updates in ALL treatment options and clinical trials. She also explains the difference between chemotherapy and immunotherapy, and talks about the potential for using venetoclax (Venclexta) to treat ALL. Watch now to learn from an ALL expert.

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Transcript | Antibodies, Immunotherapy and Clinical Trials

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Dr. Dinner:     

They have a lot of new drugs that have been recently approved for relapsed/refractory ALL. So, there’s blinatumomab (Blincyto) and inotuzumab ozogamicin (Besponsa) and even chimeric antigen receptor T cells.

Esther Schorr:            

That’s CAR T, right?

Dr. Dinner:                 

Correct.

Esther Schorr:

So, now we’re talking not about chemotherapy. We’re talking about immunotherapy or antibody therapy? Can you explain that a little bit?

Dr. Dinner::                

Right. So, these are all antibody-based therapies and they’re going through different mechanisms of using your immune system to attack your cancer essentially. And these have been studied in patients where the leukemia has come back and we know that they’re very effective. 

They do, of course, have some risks and side effects associated with them like any treatments, but we’re learning more about those and can manage them. And because they’ve been so effective for relapsed disease; we are very interested in investigating them in newly diagnosed patients to see if we can improve their outcomes, decrease the risk of relapse, and improve their long-term survival. 

Esther Schorr:            

So, why combine them with chemotherapy? Is there a difference in the way that they help treat cancer?

Dr. Dinner:

Right. So, they work differently than chemotherapy. Chemotherapy typically is going to work to kill the leukemia cell. It’s going to cause some sort of DNA damage often to the leukemia cell whereas an immunotherapy is actually going to turn on your immune system typically and try to do something with your immune system to attack the leukemia cell. So, you’re going at your leukemia from two different angles essentially.

Esther Schorr:            

Okay. And what about clinical trials?

Dr. Dinner:

So, in terms of clinical trials, that’s where a lot of these immunotherapies are moving to the front line, newly diagnosed ALL. So, recently we completed accrual of ECOG 1910, which is a trial that offers patients who achieve a minimal residual disease negative response to chemo to be randomized to get blinatumomab versus chemo alone with the hopes that blinatumomab may improve their survival outcomes. The other trial that is going on for adolescents and young adults is A041501, which is run by the Alliance for Clinical Trials in Oncology. 

And that uses a pediatric-inspired intensive chemotherapy regimen, the 10403 regimen that I had mentioned a little earlier and it adds to it, inotuzumab ozogamicin which is an antibody-drug conjugate. So that means it’s an antibody that’s connected to a drug so it can deliver it directly to the cancer cell. 

Esther Schorr:            

Almost like a cruise missile.

Dr. Dinner:

Pretty much. Yes. 

Esther Schorr:            

Now, I heard something I was just going to ask you about this if using venetoclax (Venclexta), which is used for treatment of other leukemias. Where does that fit in? 

Dr. Dinner:

So, venetoclax is FDA-approved for chronic lymphocytic leukemia and acute myeloid leukemia. It is currently being investigated in acute lymphoblastic leukemia. Here at this meeting, they will be presenting the results venetoclax and navitoclax. So venetoclax and navitoclax do is that they inhibit a certain family of proteins called Bcl-2. And when Bcl-2 is mutated; it typically will prevent the death of cells, the leukemia cells.

And so, by inhibiting those proteins, we’re then able to cause the cells to die off like they should and so it does seem as though in relapsed/refractory ALL, the study of venetoclax and navitoclax look to both B-cell and T-cell ALL. They did have good response rates of about 50 percent. 

Esther Schorr:            

Wow. So, new combinations?

Dr. Dinner:                 

Yes, and then there’s also an ongoing ECOG trial of venetoclax and liposomal vincristine (Marqibo) that’s also treating relapsed/refractory ALL with venetoclax. So, overall, we do think it’s a drug that has potential to do something in ALL.

Esther Schorr:            

So, kind of in summary, what would you say to whether its parents with a child who’s been diagnosed with ALL or an adult who gets this diagnosis? What would you say to them in terms of the field of potential treatments and outcomes?

Dr. Dinner:                 

So, I think that we’re still using chemotherapy. We haven‘t gotten rid of it all together yet, but we have so many new immunotherapies and the newer drugs like venetoclax that are targeting certain proteins that we can either use by themselves or in combination with chemotherapy and this is helping to improve outcomes. So, really in the last several years, approximately five years, there’s been a big expansion of treatment options for ALL. It’s no longer just chemotherapy.

Esther Schorr:            

So, it sounds hopeful that something that was a very difficult condition to treat; there are now beginning to be options. Is that a fair assessment?

Dr. Dinner:                 

Yes.

Esther Schorr:            

All right. Well, Dr. Dinner, thank you so much for being here and I hope this is helpful to all of you who may be dealing with ALL. This is Esther Schorr from ASH 2019 and remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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