IMS 2026 | Duffy-null genotype and transplant timing in multiple myeloma

In collaboration with my colleague Lauren Mures, who’s been a leader in the Duffy-null world broadly in hematologic oncology and in particular now with us in myeloma, we’ve made the observation that Duffy-null is much more than just a marker of leukopenia in myeloma patients. There seems to be an impact on what we see as therapeutic differences in treatment or efficacy of therapeutic approaches in different patients, especially in the context of keeping transplant in reserve versus using it early and the impact of a triplet combination, in this case, followed by transplant versus deferred. We’ve also begun to work on a working hypothesis that this is related to the inflammasome and related to the ability of patients to tolerate inflammatory stress. Our current work and the update at this meeting really drills down very rigorously on the observation of Duffy-null versus race in the context of this therapeutic difference. And the data we’re presenting is that much broader, that much bigger, that much more complete from the trial as a whole, which was over 720 patients strong, where we identified up to 20% of patients who were identified as African-American. When we drilled down on the study population overall, we distinguished differences between Duffy-null and Duffy non-null, and those patients who did not identify as being African-American who are actually Duffy-null. And we found that this relationship between treatment difference and Duffy-null was very strong, and the hazard ratio was profound. So with that in mind, this hypothesis continues to gain momentum. There are also colleagues from the MMRC, the Multiple Myeloma Research Consortium, who are presenting their analysis from the CoMMpass trial. And we have to realize the difference. The CoMMpass study is retrospective. It’s archived information, essentially. It’s historical, but still contemporaneous. Obviously, determination is prospective, randomized, multi-center, 56 centers across the United States, etc. So there are important differences. But having said that, this Duffy-null story continues to gain momentum. What in short do we see? We see that patients who are Duffy-null appear to do very well with triplet-based therapy, and we believe the same applies to quadruplets as well, although that work is in progress. And that in those patients, transplant doesn’t appear necessarily to confer any major benefit to their progression-free survival based on the fact that those who are Duffy-null and receive early transplant have a hazard ratio for clinical benefit that’s significantly less than we see for those who keep it in reserve. So does it inform a transplant decision? I think we have to be careful there. We need to know more. That’s number one. Number two, it needs to be seen in the context of the patient overall. So if you have a Duffy-null patient who for various reasons has had a wonderful response to their triplet or quadruplet therapy and basically is sitting on an excellent response with excellent tolerance of treatment and they want to collect their stem cells and keep transplant in reserve, our data would say that’s a reasonable approach. Conversely, if you have an African-American patient who’s Duffy-null with high-risk cytogenetics and doesn’t do so well with quadruplet therapy and you feel, oh, I need to consolidate with transplant, I’m not sure I would say if they were Duffy-null, I’d keep that in reserve because of Duffy-null alone. I would look at these other factors and put them together and sit down with the patient and have a very, very careful conversation about what the implications of this mean based upon what we know so far, recognizing that there’s more to follow.

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