Dr Alisha Monnette Kimble presents a large-scale, 2-phase real-world study of patients with Waldenström macroglobulinemia in the US community oncology setting, highlighting treatment patterns, survival outcomes, and the impact of socioeconomic factors and comorbidities—underscoring unmet needs beyond first-line therapy and opportunities to expand clinical research access in this population.

Alisha Monnette Kimble, PhD, MPH: Hi, my name is Alisha Kimble. I am a research scientist and I've been with Ontada now for a little more than 5 years. I've had a lot of experience in the oncology realm, focused on a breadth of pan-tumors and also hematological malignancies. Specifically, at ASCO, I've been presenting my research on Waldenström macroglobulinemia (WM).

It stemmed from an overarching study to assess the natural history of rare cancers within the US community oncology setting. This was one of the first ones that we were studying.

Can you provide an overview of your study presented at ASCO 2025?

Dr Kimble: As I mentioned, when studying the natural history of rare diseases, oftentimes it's difficult to identify this population and then, once you've identified them, be able to identify a substantial amount, enough to produce research and truly understand a patient's treatment patterns, diagnostic histories, demographics, and clinical characteristics. There's already a gap in knowledge. One of the things that we wanted to do was assess a patient's full journey within the community oncology setting.

Oftentimes, within research, not only is it challenging, as I previously mentioned, but we don't have a lot of information within the community oncology setting—so it’s more outpatient data versus inpatient, like a hospital- or academic-based setting. That was also a gap we were trying to address.

We went back a period of 10 years—from 2013 to 2022—and follow-up through 2023 to at least allow minimum of 12 months of visits so we can assess the outcomes. We looked at descriptive characteristics, demographic clinical disease characteristics, and then treatment patterns as well.

We did a 2-phased approach. First, we did a review of the entire population that we identified over the 10 years. It was a little more than 2500 patients. For them, we assessed the patient characteristics and overall survival as our main outcome. From there, we took a random sample of 200 patients, went into their charts, and did chart-abstracted analysis where we could review unstructured progress notes, scanned lab reports, and other data elements that are difficult to decipher or pull from structured, fixed-text fields. The first phase was looking at the overall population, and then we went a step deeper and looked at biomarkers and additional outcomes, including time to next treatment, time to treatment, discontinuation, progression-free survival, and overall survival.

We also did a multivariate analysis on that population where we were able to assess the associations between patient characteristics and outcomes, and how those were influencing outcomes over time. I'll just highlight some of the key findings that we identified through that.

This population is indolent in nature, meaning patients can be asymptomatic for years before actually presenting with symptoms and/or before actually receiving that first initial treatment. Through this, we were able to confirm that indolent nature, confirm the overall general demographics of this population—which are typically older White males that are diagnosed with this disease—and we were able to confirm and compare or interpret with published literature, other evidence-based guidelines such as NCCN guidelines, how this population compares to those of either academic hospital-based settings from published literature or also SEER estimates from American Cancer Society, to understand whether this population is similar to other populations. [This was also done] to provide a potential opportunity where we could be filling a gap for more clinical research to be addressed or done within this setting.

Through that, we were able to see from the treatment patterns that their patient's treatments were in line with NCCN guidelines. Rituximab-based regimens and BTK inhibitors were dominating first-line treatments as well, which is what was expected and what we are seeing in the clinical setting.

Survival rates in this population are high. Our survival rate was about 78%, and SEER reported the estimate of 76%, and this is an overall 5-year survival rate. It’s typically high in this population, but one of the unmet needs in this population is the large amount of chronic comorbid conditions that these patients go through.

Although there are high survival rates, their quality of life during this duration of time that they are diagnosed and dealing with this disease is very low. That's one of the things to remind clinicians, researchers, and the audience in general, that this population is dealing with a lot of chronic conditions over the course of this disease.

We also identified a few characteristics that were associated with outcomes, one of those being area deprivation index. This is a variable derived based on zip code. This is based on where a patient resides, whether or not they're living in more deprived areas or lower-deprived areas, and how that impacts their survival. We found that patients that were living in most deprived areas had worse survival outcomes compared to those lower-deprived areas. That's getting into access to care.

Another one of the things we identified was chronic conditions. As I previously mentioned, that's already something that impacts this population heavily, but patients that had more chronic conditions than others—and this was based on the Charleston Comorbidity Index—those patients were likely to have worse outcomes as well.

The third one was risk score. Within Waldenström, there are 2 previously validated risk stratification models, and those are derived based on lab values and they assess the severity of a disease. Ideally, if patients can be assessed using these risk models, it could give physicians prognostic tools or strategies in order to determine the treatment pathway for those patients. What we found there is patients with scores of higher risk compared to those with lower risk scores, we're more likely to have worse outcomes as well.

In your opinion, what factors contribute to the high percentage (78%) of patients initiating first-line therapy (LOT 1) with BTK inhibitors and Rituximab-based regimens, and how do these treatment choices compare to newer or emerging therapies?

Dr Kimble: These are all community oncology clinics that are part of the US Oncology Network, and they all utilize the IKnowMed electronic health record (EHR) system. Within this EHR system, it has what you call clinical pathways.

As a physician is entering a patient's data, capturing their labs, capturing their diagnoses, it will automatically suggest, based on NCCN guidelines and evidence-based guidelines, what those patients should be naturally taking. That's one of the things attributing to this high percentage as well in addition to these being regimens that are dominating first-line and recommended as the first-line choice for treatment. Both of those—the integration within the EHR system that's already hinting or guiding physicians to this, as well as the knowledge and the know-how for NCCN guidelines that also influence patient decisions and physician decisions on what the best treatment is at that time—are what's pushing this.

We did see newer or emerging therapies as we reviewed patients' later lines of therapies. For patients that progressed onto the next treatment, that's when we started seeing these treatment patterns, or at least the treatment regimens, becoming a little bit more diverse, and some of those newer therapies becoming emergent. It seems that physicians and patients are getting more creative in thinking about how they can tailor their treatment strategies to the patient's needs.

Given the impact of comorbidities and socioeconomic factors on treatment discontinuation and progression to the next therapy, how do you think care strategies can be tailored to improve outcomes for vulnerable patient populations?

Dr Kimble: This is a thing too that I think is important. Not even necessarily specifically for this disease, but other diseases as well in that access and health equity aspect. One I'll talk about—for the socioeconomic factors and specifically area deprivation index—it gives us some key insight into access to care and opening up the door for more questions in terms of the level of access to care.

Is it because of the duration from where they reside to where that clinic is? Is there a knowledge gap for those that live in more rural areas or more deprived areas where education attainment and food deserts are more prevalent in those areas? It opens the door for more conversations in terms of how we are defining or how we are evaluating what lack of access to service means for these patients.

In addition to that, looking at comorbidities, they're all tying into each other when we're thinking about distance from places, food deserts, and access to care. These patients are not only unable to receive access to care as often as others in lower-deprived areas, but it's also impacting their health overall. It's not only impacting their disease in this specific outcome, but the amount of chronic conditions that they're living with because they're not being treated for those other things as well.

In terms of strategies for improving, I think it takes a lot more communication between the providers and those patients at the onset, when those patients are coming into these clinics, and being able to recognize that these patients do live in these more deprived areas, or this patient is coming in with more chronic conditions. Let's have conversations with them upfront while we have them in the office so that we can better understand what their current conditions are and how we can best support them.

Maybe they need a couple more touch points than others who are living in lower-deprived areas. These could potentially be key indicators that give physicians or the nurses, as they're doing intake, an idea of, "Let's flag this patient and give them a little bit more attention in this setting when we first meet them."

What are the next steps for research in WM, particularly regarding the incorporation of genetic mutations like MYD88 L265P and CXCR4 into personalized treatment plans?

Dr Kimble: Great question. This was one of the things we looked at and are even suggesting for future research: opportunities for assessing outcomes based on mutation status and subtype.

In our case, because, for these 2 specifically, we were looking at the randomized subset of only 200 patients, going forward in thinking about next ideas for research would be to expand upon that and look at the overall population so we could have enough numbers and power to attest associations and understand how these different mutations are impacting patients’ care—both treatment patterns and outcomes as well.

Is there anything else you’d like our audience to take away from this study?

Dr Kimble: Overall, one of the main takeaways from this research is that there's an unmet need and a gap in knowledge in terms of patients receiving treatments after that first-line of therapy.

One of the things that we saw is, there are about 25% [of patients] that are either progressing to the next treatment or becoming relapse-refractory. That's when we started seeing introductions of newer therapies or recently approved therapies. There are changes being seen, however, patients’ outcomes over time are still dwindling. So, there's more research needed in that post-progression, relapse-refractory phase.

With this being a population within the community oncology setting, we're seeing a substantial amount of patients that are diagnosed with Waldenström. It also opens the opportunity for clinical trial research that's often done in hospital or academic based settings. But now, seeing that the numbers are there within community oncology, perhaps there could be additional clinical research coming into this space to help these patients as well or allow them to participate in trials.

So, more to come with this research and excited to be sharing with you all today. Thank you.