The Role of ASCT in the Frontline Setting for African-American Patients

This week's "Ask Dr. Durie '' comes from a patient anxious to know about the role in 2024 of autologous stem cell transplant in the early or frontline setting? And this turns out to be an important question for a number of reasons. One is, because immunotherapy, such as CAR T-cell therapy, are being discussed as possible options early in the disease and could end up being potential alternatives to autologous stem cell transplant.

But in addition to that, some important results were presented at ASH in December of 2023. These were the subgroup analyses from the DETERMINATION trial, and this is a large trial led by the Dana-Farber team in Boston with Dr. Paul Richardson as the principal investigator. This is a trial that accrued 722 patients with half receiving Velcade, Revlimid, and dex (VRd) as the frontline therapy and the other half receiving that.

But in addition, going ahead right away with that, it's all of the stem cell transplants or half got the stem cell transplant upfront. And the other half did not. In the overall results, there was a benefit in terms of the length of the remission, which was 48 months versus 65 months, in the patients who did receive the autologous stem cell transplant.

There was also overall, no improvement in overall survival. However, there was an 86% overall survival with both groups of patients. Out just a little beyond six years. But in this particular trial, 18% of the patients were African-American. And the subgroup analysis looked at, well, what happened for patients who were African-American within this trial? And very interestingly, and for the first time, the investigators showed that for women, so for African-American women who had an increased BMI who were slightly obese, these women did actually better with just the VRd alone without transplant. And that for African-American men, there was no indication of prolongation of the remission with the transplant. The results were the same with or without transplant in terms of remission; PFS. And so this was quite striking. And it was correlated with a biological thing, which was a type of blood group called DUFFY-null is a type of antigen on the surface of blood cells, which indicates a difference in the reactivity of the white cells, which could be important in response to treatment and inactivity of the myeloma.

And so, the BOTTOM LINE with this follow up of this DETERMINATION trial is that we actually do need to be a little bit more cautious about the role of autologous stem cell transplant in African-American patients. It may be that for women, it may absolutely not be necessary. And even for men, there's no apparent strong benefit. And so, this is the first clue to really try to tailor, in a logical fashion, the use of autologous stem cell transplant in this important frontline setting.