EHA 2025 | Uptake of targeted agents by race/ethnicity in patients receiving first-line treatment for CLL

As you know, here in the US, we have the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology or NCCN Guidelines for first-line regimens in patients that need therapy for CLL. And our previous research had suggested that racial and socioeconomic disparities in CLL can be reduced by providing equal access to effective CLL therapies. We had previously reported that patients with African-American or Hispanic ethnicity may not have access to this novel agent. So we wanted to see, by looking into a retrospective observational study, using a nationwide health electronic medical records called FLATIRON in a way that is de-identified what patients were being prescribed in real life. So the primary outcome was what was the preferred first-line therapy. And based on the timeline, contemporaneous with the NCCN guidelines across four time periods by race and ethnicity. And we divided, you know, by the ones that we were interested in, which was white patients, Hispanic patients, black patients, and Asian or other, and by practice type. And so we looked into the NCCN guidelines and we chose three or four time periods. One was the first one between 2016 and 2018 because the preferred first-line therapy at the time was ibrutinib. By 2019, there was a change when ibrutinib and acalabrutinib were available commercially. Also, venetoclax with obinutuzumab was available and ibrutinib. And then the other time period was 2022 onwards when you have access to zanubrutinib. The secondary outcome was the impact of the NCCN guidelines and the likelihood of the CLL patients getting what the NCCN guidelines said. Because, you know, like you can put the guidelines out there, but sometimes there are several things that may affect, you know, sometimes it’s insurance. Sometimes it’s not knowledge because the field has been moving so quickly that some physicians are not even, you know, and they see so many different diseases that they might not understand that now the preferred frontline therapy has changed. And so we looked into that. We identified over 7,500 patients that we were able to include in the study. And we discussed the demographics and what we found out was that compared with white patients, black patients were younger with a median age at receiving the first-line therapy of 68 compared to 71 years and this correlates identical to what we had seen on other prior research that we had done that for some reason that we feel might be related to some biological inherent changes, a black patient seemed to have a more aggressive disease at the time of presentation. So more black patients and Hispanic patients to the rate of 86% and 87% were treated at community practices compared to academic centers when compared with white patients that only, you know, like it was 80%. So all those patients that were tested, more black patients had unmutated IGHV than white patients. So that’s 77% against 56%. And the presence of TP53 mutation was similar across races and ethnicities, which was 11% overall, which is similar to what has been published over the last two decades, that about 10% at the time of diagnosis have a TP53 mutation. It’s interesting to see which is the unmutated IGHV in higher in patients that are black ancestry compared to white ancestry, because this is exactly what I was mentioning to you. When our group at, you know, the Feinstein Institute led by Dr Chiorazzi 25 years ago found that patients with unmutated IGHV tend to have a more aggressive course compared to patients with mutated IGHV. And at the same time, they also have a shorter survival, patients with unmutated disease. So it might be, like I said, intrinsic that because they have a higher rate of unmutated IGHV, these patients tend to require therapy much earlier, and they also may not respond to therapy for as long as a period of time compared to patients with had mutated disease. So these data are very similar to what we had published before, but this is kind of like a much larger cohort and an electronic de-identified database. And less than 20% of the patients were age younger than 65 years. Most, like I said, did not have the disease mutation. And what we found was that Hispanic patients had the lowest proportion that received the preferred frontline therapy across the four time periods, and the gap persisted and potentially widened in more than the more recent periods. And the proportion of Hispanic patients who received the preferred frontline therapy over the entire time was significantly lower than white patients. So the OR was 0.61. And there was no difference in proportion of patients overall receiving preferred frontline patients between black and white patients. So I think the disparity was more concentrated on the Hispanic population. And to me, that finding was interesting because I had also heard from colleagues that do this type of studies in myeloma that in Hispanic population, they also have lack of access to certain novel targeted agents in the Hispanic population. And I wonder if part of it is not only, you know, like where they’re treated, but also lack of insurance because many of, you know, other Hispanic patients may have difficulty having jobs that have a good insurance coverage, you know, like these are things that sometimes we don’t think and then you have to work with the patient and with the reality of what we can offer to them. And these drugs, as you know, are very expensive, at least here. In terms of the impact of the guidelines from 2016 to 2018, 44% of community practices and 55% of academic centers had already adopted targeted therapies. And I can tell you from my own experience, it took a long time from patients, even though ibrutinib was approved, to convince physicians that ibrutinib may be better than FCR. And I think it took the trial, the E1912, to get physicians to see that in reality, this drug could get you a better response with less toxicity and a longer progression-free survival compared to chemoimmunotherapy. But it wasn’t until that study that people still felt that maybe chemotherapy was the way to go because it was a fixed-version treatment strategy and it was something that they had been using for a long period of time. So I remember being, you know, that young attending saying, no, but this drug really works. And, you know, it took a long time for people to actually move away from chemotherapy into a novel targeted agent. But over time, by 2019, the ibrutinib use had increased in both practices to 77% and 67% respectively. So it had made an impact over the years, but it’s still not like 90 to 100%, which is what we would have expected. The adherence was improved over time across the practices, but decreased with the prioritization of the second-generation BTK inhibitors in 2022 to the guidelines. and after the approval of zanubrutinib, the use of targeted therapies was 71% in community practice and 74% in academic centers. Again, not 100%, which is what I would have expected, but there might be limitations based on the insurance approval and other reasons. The patients may have some cardiac toxicity and the physicians don’t feel comfortable with that. So we don’t know the details of why they chose this. It’s just that, you know, like we just wanted to know how physicians are doing these prescriptions in real life. You know, like this is just from an electronic medical record accepted, you know, that covers the whole United States. And so these updates in the NCCN guidelines actually were associated with patients receiving the preferred frontline therapy by practice type. So I think that it does help. Once you have the NCCN guidelines, it’s easier for us as physicians to also get the insurance companies to approve this drug and the coverage for the drug. But there’s still a gap in terms of academic centers versus community centers where community practices also have a little bit of a lower rate of patients initiating the preferred frontline therapy. But it got better over time. Again, you know, we had limitations in terms of confounders that we might not have measured and were not able to measure. And, you know, like 7% of the patients had no race reported, for example, and other social determinants of health may contribute. So we’re going to look and do a deeper dive on those things to understand how we can improve, because I think once you identify a deficit, then you can improve and optimize the strategies to then help deal with that, right? Like, for example, if you identify that maybe it’s an access, like maybe, and I’ve been talking to some of the societies that work with our patients here, like the Lymphoma Research Foundation and the Leukemia Lymphoma Society and the CLL Society, like if we can maybe have more access in social media, in Spanish for patients, then the patients may also tell the doctors, you know, like, I don’t want to do this chemotherapy doctor, why don’t we try this drug instead? And, you know, because sometimes, you know, we are human, and we might not be able to catch up on everything. I’m telling you, from my own perspective, it’s hard to sometimes keep up with all the novel targeted agents that are happening in other fields that I don’t see routinely. So that’s about it. It was a very interesting and humbling experience to learn that, you know, like, unfortunately, Hispanic patients, as much as we’re like a very large minority, I live in Miami, we’re 70% here. Some people are still not treated the right way. 

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