Gemtuzumab Ozogamicin for CD33+ AML and APL

Transcript:

Harry Erba, MD, PhD: Let’s turn our attention to the drug that has come back to us, gemtuzumab ozogamicin. It targets not a mutation but a cell surface marker. Rami?

Rami Komrokji, MD: This is an antibody-drug conjugate that has chemotherapy bound to the antibody that targets CD33. In my fellowship, it was approved. We use it for refractory/relapsed AML [acute myeloid leukemia] all the time, but then it was first pulled out of the market. The drug has important activity in relapsed APL [acute promyelocytic leukemia]. That’s when we used to want to get the drug back. It came back again in recent studies looking at different dosing, lower dosing in randomized trials, namely the ALFA-0701, showing a survival advantage for patients with AML, particularly the good risk. The magnitude is not minimum; the magnitude is meaningful for patients looking at the range of 20% for that 5-year survival. That’s very meaningful.

The lesson we learned is that many of those antibody-drug conjugates have to be done at the lower dose. Some of the other promising drugs, like SGN, were done at higher doses. Where do I position gemtuzumab in practice now? In patients who are good risk, they have become standard. Mark started talking about that. You want to know if those patients have core binding mutation abnormalities and other abnormalities, and you want to add it. In the intermediate, you could argue that there is some benefit, but it’s not as it is in the good-risk patients. In the high-risk patients, poor-risk patients, there is no benefit.

There are still some data about using them as single agent in patients not fit for chemotherapy. With all the promising agents we have and the toxicity profiles, I don’t think it’s often used. There was a nice abstract from your group at [The University of Texas] MD Anderson [Cancer Center] looking at eliminating anthracyclines and now doing FLAG [fludarabine, cytarabine, granulocyte colony-stimulating factor]—GO [gemtuzumab, ozogamicin] rather than FLAG [fludarabine, cytarabine, granulocyte colony-stimulating factor]–IDA [idarubicin] in the core binding showing actually almost similar results. Back to your point, maybe we are going away completely from anthracyclines.

Mark Levis, MD, PhD: We use it in high-risk APL.

Rami Komrokji, MD: Right. We’ve done the intergroup study at our clinic, the Moffitt Cancer Center.

Mark Levis, MD, PhD: It’s a huge test saver there.

Rami Komrokji, MD: Plus GO [gemtuzumab, ozogamicin]. They are looking at CPX-351 plus GO [gemtuzumab, ozogamicin] as well and other studies. That’s where I position it: in the setting of at least the good-risk patients.

Harry Erba, MD, PhD: That all sounds good, but the trouble with this drug is that it got reapproved in 2017 based on the ALFA-0701 study, which used 3 mg/m², lower dose but fractionate, days 1, 4, and 7 with chemotherapy and the MRC [United Kingdom Medical Research Council] trials that used 3 mg/m² on day 1. If you read the paper, some patients got it on day 4.

Mark Levis, MD, PhD: It’s any amount.

Harry Erba, MD, PhD: It’s any amount if the white count was high. My question to the panel is how do you dose it? Do you give 1 dose, do you give the 3 doses? What do you do?

Mark Levis, MD, PhD: We give 1 vial: 4.5 mg vial, and that’s our dose. We like to get it within 4 days of induction because that’s what the MRC did.

Naval Daver, MD: We do it with FLAG [fludarabine, cytarabine, granulocyte colony-stimulating factor]—IDA [idarubicin] and mainly in core binding cases, and we’ve used it similarly to MRC: 1 dose, 4.5 mg, just cap it. Usually day 1, but anywhere in the first 5 days is OK.

Mark Levis, MD, PhD: For APL, we’ll use a larger a dose.

Naval Daver, MD: Yeah, we use 9 mg.

Rami Komrokji, MD: We’ve had variations in using it. The challenging part for me was in the consolidation setting because the ALFA-0701, consolidated with anthracycline, you omitted the high-doses araC [cytarabine] in the good-risk patients. Sometimes I do modification in the consolidation setting, but I still like to keep the higher dose araC [cytarabine] in the good-risk patients. To be purist, one would pick 1 of the studies and follow what was done.

Transcript Edited for Clarity