New Biological Insights and Recent Therapeutic Advances in the Management of Acute and Chronic Leukemias and Myelodysplastic SyndromesEmerging data with the biallelic T-cell engaging monoclonal antibody blinatumomab as treatment for ALL
4:02 minutes.
TRANSCRIPTION:
DR KANTARJIAN: So there are several kinds of monoclonal antibodies that have been used in ALL. The first kind are the unconjugated, such as rituximab, and now ofatumumab. And they show efficacy in Burkitt leukemia and the pre-B ALL. Then you have the conjugated monoclonal antibodies, and they come in different varieties. So there’s inotuzumab conjugated to calicheamicin, moxetumomab, which is conjugated to a pseudomonas toxin. And then you have this unique blinatumomab, which is a biallelic monoclonal antibody which catches the killer T-cell, brings it in proximity to the CD19 leukemia cell and that’s the way it kills it. And I can’t recall of another example of immune therapy killing bulky disease and achieving such high complete remission rates. I think this is the proof of concept of the efficacy of the patient’s immune system in killing cells. Of course, CAR T-cells are a similar immune-mediated strategy that has a very high complete response rate. So blinatumomab was originally developed in Germany. And the original studies were with lymphoma. And what they found is that the short infusions were not working, so then they went to a 4-week continuous infusion every 6 weeks, and then they shifted to a development in acute lymphocytic leukemia. And thankfully, the results were quite positive, with marrow complete response rates in the range of 40% to 50%. Durability of those responses was about 7 to 9 months and average survival of about 12 months. And many patients were able to go to an allogeneic stem cell transplant. So this is a highly effective drug. It does have issues with the delivery of the drug, with the possibility of what looks like a cytokine release syndrome, causing fever, tremors, mental changes, occasional seizures. And the question is, how do we fit it into both our salvage and front-line therapies? I think it’s a highly effective salvage therapy. It’s there. It’s FDA approved. And what I’d like to see is more of the combined strategies sequencing chemotherapy followed by blinatumomab in both the salvage and front-line setting. DR LOVE: Are there, Doug, trials looking at using blinatumomab earlier on? DR SMITH: Yes. DR LOVE: And what’s the design? DR SMITH: Right now, there’s a cooperative group study that’s been using it. And they are looking to move it into earlier-stage disease. Obviously, the way we develop drugs, look at it, single-agent efficacy, then try to figure out how to fit it in. And when you find out it’s toxic, you remove some of the toxicities. And so we’re in a pattern where, again, with or without hyper-CVAD, for example, types of trials. DR LOVE: But nothing yet ongoing? Wendy? DR SMITH: There is a cooperative group, yes. DR STOCK: Yes. There’s a large front-line Intergroup/cooperative group study now in the United States for adults over the age of 40, actually over the age of 35 at the moment, who are newly diagnosed with precursor-B ALL to enter. It’s an intensive BFM kind of approach. And patients are going to be randomized to receiving blinatumomab or not and — DR LOVE: During the chemo? DR STOCK: No, as a separate module. DR SCHIFFER: As a block. DR STOCK: As a postremission therapy to try to reduce minimal residual disease or eradicate minimal residual disease. DR LOVE: So kind of a consolidation? DR STOCK: Yes. It’s given at a couple of different times during this treatment. And it’s a randomized study, so not all patients will be receiving blinatumomab. And the idea is that blinatumomab will improve eradication of minimal residual disease and improve disease-free survival. |