Navigating Policy and Utilization Management Oncology: Aligning Evidence With Access

Federal and state policies, including the executive order Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients (MFN) and the Inflation Reduction Act (IRA), have transformed oncology care. In a recent Peer Exchange from The American Journal of Managed Care (AJMC), moderated by Ryan Haumschild, PharmD, MS, MBA, CPEL, vice president of ambulatory pharmacy services at Emory Healthcare and Winship Cancer Institute, a panel of experts discussed how policy, payer practices, and clinical evidence intersect to shape oncology access, innovation, and affordability. They explored how aligning coverage frameworks with evolving evidence, real-world data, and patient-centered values can improve outcomes and sustain innovation in a rapidly changing health care landscape.

Impact of Recent Policies on US Health Care System and Oncology Practice

Initiatives such as the MFN executive order and the IRA have reshaped oncology care by influencing pricing transparency and reimbursement structures.^1,2 The US pays the highest prices for prescription drugs, often almost 3 times more than other developed nations.³ President Donald J. Trump introduced the MFN on May 12, 2025, to bring prices in line with those of other countries, promising a drop of between 59% and 90%. However, analysts and legal experts have criticized the policy.^3,4

Prescription drug prices in the US are set through the use of pharmacy benefit managers (PBMs), which act as intermediaries between pharmacies, health plan sponsors, pharmaceutical manufacturers, and wholesalers.⁵ The 3 largest PBMs in the US helped negotiate approximately 79% of all prescription drug claims in 2024 compared with 52% in 2004. Reports indicate that PBMs have inflated the cost of drugs, including overcharging health plans and payers through pricing schemes that are unclear, as well as pointing patients to affiliated pharmacies rather than independent ones. Calls have been made for increased transparency in PBM practices by regulatory agencies and other stakeholders.

In 2022, former President Joseph R. Biden had signed the IRA into law, which allowed the government to bypass PBMs and negotiate prices directly for several of the most costly drugs covered by Medicare Part B and Part D.² Pharmaceutical companies would be required to pay rebates to Medicare if they attempted to raise the price of their drugs at a faster rate than inflation under the IRA. The IRA also sets a cap on out-of-pocket spending for Medicare Part D. According to research findings, pre-IRA list prices for 10 IRA-negotiated drugs in the US were 5.6 times the levels in France and Germany (accounting for existing Medicare rebates).⁶ The gap decreased to 3.2 times the French and German prices following IRA negotiations.⁶ Although the cuts narrowed the difference, US prices remained higher than those in Europe, even after negotiation. In addition, although policies aim to reduce medication costs, they often introduce administrative complexities that affect timely access to treatments.

Value-based frameworks and outcome-driven reimbursement models increasingly guide payer decisions. The challenge for policy makers is to balance cost containment with clinical nuance, ensuring that reforms do not inadvertently restrict access to lifesaving therapies or discourage investment in research and innovation.

Stakeholder Insights

“The past 5 years really have been very impactful from a policy standpoint,” said Olalekan Ajayi, PharmD, MBA, FACCC,chief operating officer at Highlands Oncology Group in Northwest Arkansas and former president of the Association of Cancer Care Centers. “While the intent is to make oncology care more affordable, implementation inconsistencies can hinder providers’ ability to deliver evidence-based care efficiently. It means that we’re going to have to rethink the way that we’re looking [at] and delivering care to patients…from a drug negotiation standpoint all the way to just making sure that we’re beginning to go into value-based care strategies rather than fee-for-service.”

Nick Bouchard, PharmD, director of pharmacy services at Hematology-Oncology Associates of Central New York, discussed the added pressures on the challenges the practice is already facing. “One of the biggest benefits with the IRA for us was the $2000 out-of-pocket max [in 2025] that is going up to $2100 in 2026. But we saw a shift in our practice where we did have a lot of patients who…couldn’t afford their out-of-pocket [costs], and they were then sent to an assistance program provided by a manufacturer, typically. Many more patients could afford the $2000, right? So that meant that now they have access to the medication, and they have access to the medication from our practice.… [So it’s] kind of getting rid of some of those access barriers for those patients.”

Role of PBMs in Oncology

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, clinical pharmacy manager in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Health System in Kansas City, discussed the role of PBMs. “They play such a significant role in shaping which oncology therapies are accessible and under what conditions. We know that consolidation has significantly increased,…so what we’re seeing is greater standardization of formulary pathways nationally. And we know that they’re exerting their growing influence through contracted pharmacies, step edits, and mandatory specialty pharmacy channels.… So while that can, on one hand, bring consistency, it also means that coverage decisions may not always keep pace with the nuanced clinical data…. Over the past 5 years, we’ve seen oncology prior authorization requirements [increase by approximately] 30% to 60%. Frontline teams are seeing that added review steps…can sometimes lead to delays in care; we have all tracked that from our specialty pharmacies. We all know [that] in the setting of cancer care, timing really matters.”

She added that using mandated external specialty pharmacies also introduces coordination challenges for those in the frontline setting, particularly around dosing education and delivery timelines. “I can’t emphasize enough [the] administrative burden on our clinical staff when we are actively dealing with some significant changes in the hematology space.”

As policies push for pricing transparency and rebate reform, PBMs may initially respond by tightening the utilization management, according to Mahmoudjafari. “We’ll see more tiers, perhaps narrow formularies to aggressive fail-first approaches to protect the margins, to maintain value as much as possible.”

She added that there are early signs of regulatory scrutiny, which will drive PBMs to justify medical appropriateness and align more closely with clinical guidance and toxicity signals. “I certainly anticipate the increased use of real-world evidence dashboards and risk-stratified exceptions and guidance alignments ideally with NCCN [National Comprehensive Cancer Network].… Now, if we see…the PBM shift toward clinical outcomes contracting, we’ll certainly start seeing better alignment.”

Taral Patel, MD, medical oncologist at Zangmeister Cancer Center in Columbus, Ohio, said he had been engaging with PBMs for more than 27 years but is “not finding any pros. The problem is [that the] PBM is looking at what’s best for them, not [at what’s] best for the patient. [For example], they try to dictate what agent we should use when we have multiple agents, but they don’t know the patient....”

Patel’s practice has a specialty pharmacy serving 170 physicians that was attempting to retain a contract with one of the insurance companies. They were able to prove they had less waste than the PBM standard, allowing them to keep the contract. “The reason is [that] we have pharmacies in-house; they call the patient every time before they dispense any prescription…. So they know exactly what the patient needs. [The] patient doesn’t have the scan, [but the pharmacy] can look at it, [see] progressive disease, [and] change the dose…. So we can save a lot of money by…having control rather than the PBM having control.”

Challenges of Step Edits in Oncology

Bouchard discussed how step edits, requirements for patients to try less costly therapies before accessing preferred treatments, create barriers in oncology. “Step edits are probably one of the biggest issues we’re seeing lately. I feel like there’s definitely been a rise in step edits, especially with some of the IRA changes in 2026. They’re [putting] step edits in place that are maybe not the best therapy available.… It could take an additional, if you’re lucky, 3 or 4 days, but typically, it’s much longer than that; usually, it’s 7 to 14 days.” Going through an appeals process, “providing information to the payer on clinical studies that show the advantages of one drug over another and why you want to use that particular drug, hoping that they will read it and...overturn their decision to [put] the step in place, means the patient’s waiting.”

Patel agreed that the PBMs use step edits as a tactic to delay treatment: “I think it’s an everyday battle.… So you can imagine if you have 100,000 patients, [and] you delay the treatment by 2 weeks, how much money they saved.” He said that they often end up approving treatment. “So why didn’t [you] approve the treatment before? Why [did] you [wait] 10 working days? That’s the biggest headache, and [it results in] anxiety for the patient.”

Ajayi discussed how coverage policies frequently lag scientific advances in oncology. “Think about the accelerated pathway that the FDA employs to bring drugs [more quickly] to the market. What we’ve seen is payer policies have lagged with that, often leading to demand for either more data or things like more information for them to get that approved.” He also sees this with genetic testing, “where payers often discourage broad genetic testing for patients…. Also, when you start to think about things like [circulating tumor DNA] vs tissue biopsy, and a lot of payers often demanding that we do tissue biopsy all the time, that again slows down care for the patient…as well,...and it really denies access to lifesaving medications for patients.”

Exploring the Disconnect between Clinical Data and Coverage Decisions

B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma, comprise the most common hematologic malignancies.⁷ Bruton tyrosine kinase (BTK) is a key component of the B-cell receptor signaling pathway in various B-cell malignancies. It is specifically targeted by covalent BTK inhibitors (BTKis), whose development has transformed CLL management.⁷ Ibrutinib was the first BTKi approved for the treatment of CLL in 2013.⁷ Acalabrutinib and zanubrutinib are second-generation BTKis, developed to minimize off-target effects, and were approved in 2017 and 2019, respectively.⁷

The efficacy and safety of acalabrutinib were directly compared with those of ibrutinib in adults with relapsed/refractory (R/R) CLL in the phase 3 ELEVATE-RR study (NCT02477696).^8,9 After a median follow-up of 40.9 months, acalabrutinib showed noninferiority in progression-free survival (PFS) to ibrutinib (HR, 1.0; 95% CI, 0.79-1.27), with a lower incidence of adverse events.⁸ Atrial fibrillation or atrial flutter of any grade occurred less frequently after treatment with acalabrutinib than with ibrutinib in 9.4% and 16.0% of patients, respectively.⁸

In the ALPINE trial (NCT03734016), the efficacy and safety of zanubrutinib were compared with those of ibrutinib in adults with R/R CLL.⁹ In the final analysis, after a median follow-up of 42.5 months, PFS and overall response rate (ORR) were higher with zanubrutinib than with ibrutinib (PFS: HR, 0.68; 95% CI, 0.54-0.84; ORR: 85.6% vs 75.4%; response ratio, 1.13; 95% CI, 1.05-1.22).¹⁰ Adverse events were lower with zanubrutinib than with ibrutinib, including cardiac events (25.9% vs 35.5%) and atrial fibrillation/flutter (7.1% vs 17.0%). No cardiac deaths were reported with zanubrutinib compared with 6 cardiac deaths with ibrutinib.¹⁰

Based on the findings of phase 3 randomized trials, acalabrutinib and zanubrutinib received broad FDA approval for patients with untreated and R/R CLL. The use of acalabrutinib and zanubrutinib is included as a preferred first-line (1L) treatment option over ibrutinib in NCCN guidelines.¹¹ 

Stakeholder Insights

Disconnect Between NCCN Guidelines and Coverage Decisions for BTK Inhibitors in CLL and the Impact

Patel explained how payer coverage often diverges from practice guidelines, particularly in the use of BTKis for CLL. Although NCCN recommendations prioritize newer, safer agents such as acalabrutinib and zanubrutinib, many payers still restrict access to older therapies such as ibrutinib due to cost considerations. “It’s all about the toxicity. So you want to have the best, safest BTK inhibitor use, not the cheapest one…if you get atrial fibrillation, if you get a cardiac event, and if you look at that 2% fatal rate, [for] every hundred patients you’re going to give that BTK inhibitor [to], it could be less expensive, but you’re going to have 2 patients die from that treatment.”

According to Ajayi, payer coverage decisions differ significantly from guidelines in practice. “[For] NCCN, the focus and the incentives…is to provide the best [and safest] care...to the patient, right? However, what we’ve seen with...the payers [is that] their policies are geared more toward formulary control and cost control.”

Panelists agreed that forced step edits can increase adverse events, treatment discontinuations, and overall health care costs: “There’s this constant need for payers to force you through this funnel of having to use ibrutinib first,” Ajayi said. “We all know ibrutinib comes with all sorts of cardiovascular toxicities.… So that’s an ongoing battle in the CLL space right now, where providers feel that there are times when their hands are tied in using a treatment that they might regard as suboptimal for their patients.”

“We’re actually very privileged here in that we do have comparative evidence in the BTK inhibitor space,” Mahmoudjafari said. “Many patients [with CLL] are older; they have cardiovascular comorbidities. And so, these differences, if you [give] preference [to] ibrutinib first, can impact quality of life and overall impact continuity of care.… These can certainly translate into real hospitalizations, stream interruptions, and, of course, cost escalation.” She added that management with anticoagulation could increase the workload and that it often comes with drug interactions. “We’ll see higher therapy abandonment. We’ll also see that earlier loss of sequencing.… Something to continue to keep in mind is that cheaper is not always actually cheaper in reality.”

Bouchard agreed: “I think coverage decisions should be determined by up-to-date guidelines. That’s the first step. And I do think that payers typically follow guidelines. They’re looking at NCCN guidelines, and they’re looking at FDA labels, but they’re not taking it any…further.… You really need to look at the most up-to-date clinical evidence as well.… You have real-world evidence studies coming out that show the superiority of one drug over another.… They don’t know the patient has a history of [atrial fibrillation] and maybe this isn’t the correct drug for them. Maybe they don’t know if the patient has a history of a bleeding disorder, and this may not be the correct drug for them.… We need to look at what the best clinical evidence is [and] what the best outcome is that we can perceive for these patients. And that’s the drug that should be chosen.”

Use of Real-World Evidence of BTKIs and Patient-Centered Values to Inform Coverage Decisions in CLL

Real-world evidence can provide valuable insights for refining coverage policies in oncology, particularly for the use of BTKis in CLL. In a retrospective single-practice study, investigators examined real-world treatment patterns in patients with CLL/SLL who were treatment naive or had received prior ibrutinib after a practice change to zanubrutinib (N = 281).¹² Cardiotoxicity exposure–adjusted incidence rates were higher with ibrutinib than with zanubrutinib. Eleven patients developed atrial fibrillation on ibrutinib compared with 4 patients on zanubrutinib, leading to discontinuation in 3 and 1 patients, respectively.¹²

A retrospective observational study (N = 2515) using the nationwide Flatiron Health database included patients with a CLL diagnosis who started first-line BTKi monotherapy (ibrutinib, acalabrutinib, or zanubrutinib) between January 2020 and August 2024.¹³ Median real-world time to treatment discontinuation or death (rwTTD) was not reached for zanubrutinib, 43.7 months for acalabrutinib, and 21.9 months for ibrutinib. Patients receiving zanubrutinib had statistically significant lower risks of real-world time to next treatment or death (HR, 0.59; 95% CI, 0.44-0.79), rwTTD (HR, 0.56; 95% CI, 0.44-0.72), and real-world overall survival (HR, 0.46; 95% CI, 0.28-0.76) than patients receiving ibrutinib, and numerically lower risks than those receiving acalabrutinib.¹³

A retrospective observational study using the Symphony Health Solutions Integrated Dataverse, an open-claims database, included adults with CLL undergoing a 1L BTKi treatment regimen (zanubrutinib, acalabrutinib, or ibrutinib) from February 2022 through September 2024 (N = 6846).¹⁴ Data from this real-world study showed that across all patients with CLL, those treated with zanubrutinib had a longer time to discontinuation, lower discontinuation rates, and less health care resource utilization than those treated with acalabrutinib or ibrutinib, including patients 65 years or older.¹⁴

Stakeholder Insights

Mahmoudjafari said that data from real-world studies provide insight into a broader, older, and more comorbid population of patients, providing a more realistic snapshot of what they have and the patients they are trying to treat. Cardiotoxicity signals and comorbidities increase with patient age, and the cost of toxicity can be “anywhere from $7000 to $25,000 or more per hospitalization.… I think they should be incorporating real-world evidence in quarterly or semiannual formulary reviews, really taking into consideration the reports and the time that it takes for us to report this real-world evidence. One of the other places that real-world evidence can be utilized is triggering automatic step edit removal when these toxicity thresholds are exceeded.… We know that oncology is evolving. It evolves rapidly. Our policies have to evolve with it.”

Ajayi explained that black box warnings, although essential for patient safety, often create disproportionate barriers in oncology coverage. “This is one area where, again, there’s a mismatch. And this is probably where you’d expect maybe payers to get more aggressive, but then you see that they’re not.… What we see is the potential of...inappropriate drugs going out to the patient as a result of these decisions.”

Impact of Utilization Management on Physician Autonomy and Shared Decision-Making in Oncology

Patel noted that increasing utilization management oversight affects physician autonomy and the shared decision-making process in oncology, including CLL. “I’ll tell [the patient to] come back in 4 to 6 weeks, because once you know what you send—the prescription—a lot of things need to [happen] behind the scenes before you get approved and patients get the treatment or get shipment to their home.” He said that created additional anxiety for the patient and a lot of office time for clinicians, “the pharmacy, pharmacy technician, [and the nurse practitioner] in my case, and then it comes to the physician. So we have 4 people involved to approve the 1 treatment, which, in my opinion, is a lot of administrative burden.”

The question is: How do clinicians even discuss the disconnect between coverage policy and clinical trial data in shared treatment decision-making? Patel tells the patient, “This is my preferred treatment and why, and if your insurance disagrees with that, then I’ll call you back and say what’s acceptable…. Sometimes I’ll tell them, ‘Go to your human resource [department], tell them to call them, because they’re not approving the best treatment for you,’.… But again, it’s a delay in the treatment.”

Shaping Oncology Policy Through Access and Safety Considerations

Mahmoudjafari highlighted some of the issues with step edits and the impacts and risks that we see regarding safety. “Step edits that utilize BTK inhibitors as equivalent ignore differences in the cardiovascular toxicities. There are differences in headache and bleeding profiles. There [are] treatment persistence rate differences.” She explained that with zanubrutinib, “we have 78% to 84% persistence at 12 months, whereas with ibrutinib, the data demonstrate 55% to 60%.… We know when a patient discontinues for any sort of toxicities, not necessarily for disease progression, we lose that opportunity to leverage a different agent for future sequencing opportunities. We narrow that therapeutic window. And certainly, we see a rise in acceleration of resistance.”

Ajayi shared his thoughts on which payer policy changes would help align the coverage of BTKis or other oncology agents with clinical evidence to ensure patient safety. “I think you have to [have] a multipronged approach to be able to do this. When I was the president of the Association of Cancer Care Centers, one of the things that we really advocated for was around safety and efficacy parity,…that if you had a group of medications that were within the same class, and you’ve got 1 or 2 that are at least noninferior or superior, we should not have to do step therapy for those drugs.… We went to Congress,…and we try to fight from a legislative standpoint at a federal level. But we all know how difficult it is to get anything through Congress these days, so we’ve done a lot of work at the state level to ensure parity for these medications. And I will tell you [that] we’ve seen more success when done more at a state level than when trying to do it federally.”

He added that “real-world evidence provides you with information to have a conversation with insurance companies to say, ‘Hey, here is what our data [are] telling us. How can we involve this in payer formulary decisions? ’… One other piece that we can’t forget that [also] ties into this…is patient-reported outcomes,…being able to catalog patient-reported outcomes and to be able to use that as a way to buttress their compensations either with insurance companies or with their lawmakers.… I can’t overstate the importance of having a reflex-type policy that approves broad testing for genetic markers for patients. I think that really provides them [with] the opportunity to get on their therapy that they need to get on much more quickly. I think those are the gaps that we need to cover.”

Implications of IRA Drug Pricing Negotiations on BTKis in CLL

Bouchard commented: “I think some of the economic impact could inadvertently actually increase.… Recent study [data]…showed [that for] a patient on acalabrutinib, [the] total cost of care over 1 year of therapy was about $15,478 less than that patient on ibrutinib. And that was because they took into account…the adverse events and the management of those adverse events…associated with ibrutinib.”

Ajayi agreed: “The IRA is probably going to be…one of the most consequential policies that will affect us for probably the next 10 years or more.… It gives Medicare the ability to negotiate drug prices for certain Part B drugs that have probably been in the market for at least 7 years and really don’t have any biosimilar alternative out there.” Other key provisions in the IRA include one that advises manufacturers not to raise drug prices more than inflation, year on year, or they will face penalties, and one that caps patients’ spending.

Bouchard wondered how manufacturers would respond. Will the costs for those first 5 to 7 years on the market be higher than they are now, which would be another unintended consequence of the IRA? He believes that the IRA and the focus on cost containment will give the PBMs considerable power. “I think if the IRA is targeting particular drugs for cost containment, that kind of gives the PBMs a little bit of the power to set preferences, set step edits, etc. So again, I think that there’s definitely going to be a disconnect between clinical evidence and cost.”

Mahmoudjafari commented that expected price reductions for ibrutinib in 2026 under the IRA’s price negotiation program might shape coverage decisions. In addition, acalabrutinib will enter price negotiation in 2027, but no price negotiation is planned for zanubrutinib. “There are a lot of implications here that we can think about, and we can already see it, as we know that with negotiated prices…we expect that their payer colleagues may preferentially steer patients toward ibrutinib because it’s that contracted budget saver.… Lower drug costs should be considered alongside real-world tolerability and the supportive care needs that accompany these certain toxicity profiles.… Ideally, we want to have coverage frameworks that incorporate NCCN alignment, looking at the individual patient comorbidity profiles, emerging data, and being very efficient with emerging data and looking at making coverage decisions based on that.”

Bouchard discussed patient affordability and access to some of these newer and more expensive cancer therapies. “They’re still pricey drugs, and I feel like they’re still going to be in that $2000-plus range out of pocket.… I do see an impact on accessibility because now you might, again, have preferences for older-generation drugs…because of cost. So I do see some dwindling access to some of the newer cancer therapies.… I don’t think anybody wants to be on the list from a manufacturer’s perspective for the IRA-negotiated drugs.”

Future of Oncology Research in a Shifting Policy Landscape

Patel believed research and development may slow down while the focus is on keeping products out of the IRA when they can generate the most benefit elsewhere. He foresees that the number of indications for a drug might be reduced when expected returns are lower. “I don’t think we could see any drug with 80 indications anymore. They can stop the development after 8, 10 indications.… Why invest more money when the return will be lower? So stop it here, and let’s move on to the next drug.”

Bouchard agreed: “There’s been a 30% decrease in drugs that are already approved for expanded indications, especially in that small molecule space, or [where] that roadway is much shorter than the large molecule.”

Mahmoudjafari added, “I think we may very easily see a potential shift toward biologics or novel modalities and high-spend assets because we know the biologics have a later negotiation eligibility, so that’s a longer exclusivity window before negotiation.… There [are] some natural implications for investigator-led research here. And certainly for us in clinical practice, looking at budget and operational considerations.”

Patient access is important, Ajayi said. Further investment in complex therapies could mean that patients need to travel farther to access them. “We’ve seen things like that with [chimeric antigen receptor] T cell therapies [and], to some extent, bispecific therapies…particularly for rural patients, where all of a sudden, your local cancer center is not equipped to deliver these lifesaving medications to you, and you have to travel far. I think that’s going to be an unintended consequence…of the IRA.”

Importance of Engagement and Education

“My experience has been [to] think globally, act locally,” Ajayi said. “Take the time to learn about all these policies and how they’re going to affect you. Get active about engaging stakeholders to ensure that you’re getting this optimal environment to take care of your patients.”

Bouchard agreed: “I think we all need to be educated in our field [and on] how this is going to affect our practices. How do these policies affect our practices and therefore trickle down to our patients? I think it’s important that we use our voices.”

Mahmoudjafari mentioned that she has had the opportunity to speak to many payer colleagues. “It’s a partnership, and it relies on us to educate them, inform them of the consequences, and make sure that it’s really a team-based approach. We each have to come to the table and be really honest and forthcoming with the challenges that we have,…really making sure that we align evidence with policy and help advocate.… We have to continue to advocate to our legislators, and we have to continue to advocate with our payer colleagues, because they have their challenges and they have all these lives that they need to make sure are covered, but not at the expense of this really critical patient population.”

“There is an ecosystem, and payers are part of the care delivery,” Haumschild said. “So how do we bring the evidence and make sure they’re engaged [and] making the most informed decision that allows for those best outcomes and total cost of care and not just product cost alone?” •

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