Inflation Reduction Act Impact on the Hematology/Oncology Treatment Landscape

ABSTRACT

The Inflation Reduction Act (IRA) represents a transformative shift in US health care policy by enabling Medicare to negotiate drug prices for high-expenditure medications, with significant implications for hematology and oncology treatment. This commentary explores the potential clinical impact of the IRA on selected cancer therapies and cancer-related supportive care agents, including apixaban (Eliquis), rivaroxaban (Xarelto), ibrutinib (Imbruvica), acalabrutinib (Calquence), enzalutamide (Xtandi), palbociclib (Ibrance), and pomalidomide (Pomalyst). These agents, used across various cancer types including chronic lymphocytic leukemia, prostate cancer, breast cancer, and multiple myeloma, are central to current treatment paradigms and have high utilization among the Medicare population. The IRA’s negotiated pricing may improve drug affordability and access, influence prescribing patterns, and shift prescribing practice. However, clinical considerations, including efficacy, toxicity profiles, and overall survival benefits, remain critical in guiding therapeutic decisions. As cost-effectiveness analyses evolve in response to pricing changes, the IRA may ultimately reshape the oncology treatment landscape by aligning economic value with patient-centered care.

Am J Manag Care. 2026;32(3):133-137. https://doi.org/10.37765/ajmc.2026.89891

Takeaway Points

The Inflation Reduction Act (IRA) introduced Medicare drug price negotiations to reduce treatment costs, enhance access, and potentially reshape prescribing patterns in oncology and hematology.

• The IRA targets high-expenditure Medicare Part D drugs, with projected savings of $1.5 billion in 2026.
• Price negotiations may lead to prescribers favoring drugs such as apixaban, rivaroxaban, and ibrutinib due to lower costs.
• Economic shifts could influence Bruton tyrosine kinase inhibitor and antiandrogen prescribing decisions despite clinical preferences.
• Lower pricing on drugs such as enzalutamide and palbociclib may improve affordability but not necessarily alter clinical guidelines.

The Inflation Reduction Act (IRA) drug price negotiations mark a significant milestone, as they empower the federal government to negotiate drug prices on behalf of Medicare. The US government historically could set a maximum fair price on generic drugs, but the price of branded drugs was traditionally determined by the manufacturers. For drugs used to treat diseases common in the older population, the IRA price-setting process is projected to yield savings of $1.5 billion in 2026 after the first round of negotiations.¹ The drugs are selected from those with the top 50 highest gross spending under Medicare Part D within the past 12 months. To qualify, drugs must have been approved for at least 7 years, except for biologic agents, which require approval for at least 11 years, and they must have no generic and biosimilar competition. The IRA price negotiations may also impact the treatment landscapes of certain disease states. In the first 2 negotiation cycles, several anticancer and cancer-related supportive care agents were selected, including apixaban (Eliquis), rivaroxaban (Xarelto), and ibrutinib (Imbruvica) in the first cycle (prices effective 2026) and acalabrutinib (Calquence), enzalutamide (Xtandi), palbociclib (Ibrance), and pomalidomide (Pomalyst) in the second cycle (prices effective 2027). This commentary discusses current treatment guideline recommendations, available pharmacoeconomic studies, and the potential impact of the IRA price negotiations on the hematology and oncology treatment landscape.

Apixaban and Rivaroxaban

Direct oral anticoagulants (DOACs) have emerged in recent years as preferred therapies in the treatment of cancer-associated venous thromboembolism (CA-VTE) and as prophylaxis for medical oncology patients who are at an increased risk for developing CA-VTE.^2-6 These therapies have largely replaced low-molecular-weight heparins in CA-VTE treatment due to their convenience of oral administration and evidence supporting their safety and efficacy over dalteparin (Fragmin). Apixaban, rivaroxaban, dabigatran (Pradaxa), and edoxaban (Savaysa) all have recommendations for treatment in CA-VTE, and apixaban and rivaroxaban have recommendations as prophylaxis.^7,8

Although the literature evaluating real-world prescribing patterns among the DOACs in CA-VTE is relatively sparse, available evidence suggests that apixaban and rivaroxaban are the predominantly utilized DOACs in the US for CA-VTE.^9,10 This likely stems from experiences of using these therapies prior to major trials evaluating their use in CA-VTE and that there are no requirements for them to be preceded by parenteral anticoagulation, as is the case with edoxaban and dabigatran.

Based on current practices, the IRA may continue to shift prescribing patterns for CA-VTE toward apixaban and rivaroxaban and continue to limit the use of edoxaban and dabigatran. Apixaban and rivaroxaban were among the drugs with highest Medicare Part D gross spending in 2021.¹¹ Because DOACs are now already widely utilized as a standard of care for CA-VTE in the US, the IRA is expected to lower the total cost of care for the treatment of CA-VTE and improve the pharmacoeconomic profile of DOACs in this therapeutic space. This may be further impacted in due time by the impending patent expirations and generic drug development for both rivaroxaban and apixaban expected in the coming years.

Ibrutinib and Acalabrutinib

Bruton tyrosine kinase (BTK) inhibitors, including ibrutinib and acalabrutinib, are utilized in the treatment of non-Hodgkin lymphomas, which collectively have a median age of diagnosis of 68 years and 5-year relative survival rates near 75%.¹² Second-generation BTK inhibitors, including acalabrutinib and zanubrutinib (Brukinsa), are utilized as monotherapy or in combination therapy and serve as preferred frontline and subsequent-line treatment options for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with or without 17p deletions/TP53 mutations and mantle cell lymphoma (MCL). Ibrutinib, the first-in-class and a first-generation BTK inhibitor, is a recommended frontline and subsequent-line treatment option for CLL/SLL and a recommended subsequent-line option for MCL in the National Comprehensive Cancer Network (NCCN) guidelines.^13,14 BTK inhibitor–based therapy is frequently administered continuously until progression or unacceptable tolerability in CLL/SLL and MCL, with the exception of the recent guideline addition of fixed-duration acalabrutinib in combination with venetoclax (Venclexta) with or without obinutuzumab (Gazyva) in CLL/SLL.¹³

The greatest impact of the IRA on the CLL/SLL and MCL treatment landscapes is expected for patients for whom the best frontline or subsequent-line treatment option is BTK inhibitor monotherapy. In an analysis of Medicare Part D spending on CLL drugs, ibrutinib costs and prescribing rates rose between 2014 and 2020 despite FDA approval of acalabrutinib and zanubrutinib during this time frame.¹⁵ Ibrutinib at the negotiated maximum fair price demonstrated cost-effectiveness relative to acalabrutinib and zanubrutinib in frontline and subsequent-line CLL settings.¹⁶ However, zanubrutinib and acalabrutinib are currently clinically preferred over ibrutinib due to noninferior (acalabrutinib) or significantly longer (zanubrutinib) progression-free survival (PFS) and more favorable cardiovascular safety profiles in comparative effectiveness evaluations with ibrutinib in the population with previously treated CLL.^17,18 Prior cost analyses comparing acalabrutinib and zanubrutinib and their safety profiles in health economic models have demonstrated mixed results: Acalabrutinib yielded cost savings in patients with CLL,¹⁹ whereas zanubrutinib produced cost savings and quality-adjusted life-year (QALY) gains in patients with B-cell lymphomas.²⁰ In therapy decision-making between acalabrutinib and zanubrutinib monotherapy in CLL/SLL and MCL, acalabrutinib utilization may increase given its inclusion on the 2027 IRA list and lower expected cumulative prescription drug costs for Medicare patients. The inclusion of ibrutinib on the 2026 IRA list could reestablish it as a CLL/SLL or MCL treatment option in a patient whose best next treatment is a BTK inhibitor who is unable to access acalabrutinib or zanubrutinib and who does not have a significant cardiac history.

Enzalutamide

Among the Medicare population, prostate cancer is included in 6.5% of medical claims,²¹ and approximately 70% of the cost of prostate cancer management is related to treatment costs.²² Within the metastatic subsection of prostate cancer, enzalutamide is a preferred recommendation in the NCCN guidelines for castration-naive, castration-sensitive, and castration-resistant prostate cancer.²³ Enzalutamide is also included as a recommended agent in the nonmetastatic castration-resistant population.²³ Other guideline recommendations include the novelsecond-generation antiandrogens apalutamide (Erleada) and darolutamide (Nubeqa) as well as abiraterone (Zytiga), an androgen synthesis CYP17 inhibitor.

In the metastatic castration-naive or castration-sensitive population, the NCCN guidelines recommend abiraterone, enzalutamide, and apalutamide in doublet therapy with androgen deprivation therapy (ADT).²³ Despite multiple options listed in the guidelines, abiraterone is the only treatment available generically and may be the only option if the branded second-generation antiandrogens are price prohibitive. In a meta-analysis of 7 clinical trials from the US health care perspective, branded enzalutamide and apalutamide were not cost-effective.²⁴ Generic abiraterone had a higher willingness-to-pay threshold but was still cost-effective given its higher QALYs than docetaxel.²⁴ In this meta-analysis, the mean QALY gain from enzalutamide was less than that from abiraterone (3.92 vs 4.73 QALYs).²⁴ From a cost-effectiveness perspective, the IRA pricing of enzalutamide may improve its incremental cost-effectiveness ratio, providing an option for Medicare patients who wish to use an antiandrogen for clinical benefit and a preferred adverse event (AE) profile but for whom it was previously cost prohibitive. The enzalutamide IRA pricing may provide a way for antiandrogens to be more affordable in the metastatic castration-sensitive setting.

In patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel, abiraterone and enzalutamide have both been shown to improve overall survival (OS) compared with placebo.^25,26 Study findings suggest that the sequencing of docetaxel and abiraterone up front may improve treatment outcomes.^27,28 This evidence for sequencing may push enzalutamide to later treatment lines where efficacy has not been established. Current studies have shown that generic abiraterone is more cost-effective than ADT alone or enzalutamide in mCRPC.²⁹ Updated cost-effectiveness analyses with IRA pricing of enzalutamide may help justify its use over abiraterone in the mCRPC setting.

In the nonmetastatic castration-resistant population with a prostate-specific antigen doubling time of less than 10 months, all 3 novel antiandrogens (enzalutamide, darolutamide, and apalutamide) have preferred recommendations in the NCCN guidelines.²³ With lower enzalutamide pricing, the market will likely shift in favor of enzalutamide in this setting.

Palbociclib

Hormone receptor–positive (HR+)/HER2+ breast cancer represents 70% of female breast cancer cases diagnosed each year.³⁰ Cyclin-dependent kinase (CDK) 4/6 inhibitors in combination with endocrine therapy such as aromatase inhibitors (AIs) or fulvestrant (Faslodex) have become a mainstay of first-line treatment for HR+ metastatic breast cancer.³¹ The CDK4/6 inhibitor class consists of palbociclib, abemaciclib (Verzenio), and ribociclib (Kisqali). All 3 FDA-approved CDK4/6 inhibitors have demonstrated improved PFS when added to standard endocrine therapy vs endocrine therapy alone in the first-line and subsequent settings.^32-45 Notably, only ribociclib plus an AI, ribociclib plus fulvestrant, and abemaciclib plus fulvestrant have demonstrated a statistically significant improvement in OS.^38-40,43 However, no comparative effectiveness studies have been conducted. Although the CDK4/6 inhibitors are considered reasonable options for first-line and subsequent treatment of HR+ metastatic breast cancer, ribociclib plus an AI or fulvestrant and abemaciclib with fulvestrant are designated as preferred NCCN guideline options given their OS benefit; palbociclib plus an AI or fulvestrant and abemaciclib with an AI are category 2A preferred.³¹ When choosing among several options within the same class of medications, consider prior treatment tolerance and concurrent disease states to select the best initial treatment option in this setting.

As a class, CDK4/6 inhibitors may also be differentiated by their toxicity profiles. Palbociclib and ribociclib demonstrate higher rates of hematologic toxicity, notably neutropenia, than abemaciclib.^34,46 Conversely, diarrhea is more common with abemaciclib.³² Ribociclib requires Fridericia-corrected QT interval (QTcF) monitoring per FDA labeling given QTc prolongation demonstrated in clinical trials; patients with a baseline QTcF greater than 450 milliseconds are not eligible to initiate treatment with ribociclib, and increased monitoring may be required when QTc prolongation occurs or if inciting medications are initiated during treatment.⁴⁷ This may contribute to increased costs for additional monitoring visits and/or electrocardiogram testing. Data from a recent retrospective study showed that total health care costs associated with palbociclib may be lower than those of abemaciclib and ribociclib.⁴⁸ Palbociclib may serve as a preferred option for patients with preexisting cardiac and/or gastrointestinal concerns where tolerance of ribociclib or abemaciclib may prove problematic.

Evidence demonstrating improved OS is a compelling clinical reason for choosing ribociclib or abemaciclib over palbociclib in the metastatic setting—barring patient-specific considerations for choosing an alternative CDK4/6 inhibitor—and is reflected in current guideline preferences. Recent economic evaluations, however, have demonstrated that none of the currently approved CDK4/6 inhibitors demonstrate cost-effectiveness given their modest QALY gains and high treatment pricing.^49,50 Palbociclib’s selection for the 2027 Medicare drug price negotiations will improve access to an effective breast cancer treatment option by lowering costs to Medicare patients but is not likely to alter the current treatment paradigm given the OS benefit demonstrated by alternative CDK4/6 inhibitors.

Pomalidomide

Multiple myeloma is a plasma cell disorder that accounts for approximately 1.8% of all cancers in the US, with a 5-year relative survival rate of 62.4%.⁵¹ It is presently considered an incurable cancer,⁵¹ and as a result, patients typically undergo intermittent treatment throughout their lifetime, which can impose a significant ongoing financial burden.

Immunomodulatory drugs (IMiDs), including lenalidomide (Revlimid) and pomalidomide, play a crucial role in the backbone of treatment for relapsed or refractory (R/R) multiple myeloma. The current treatment landscape is to use lenalidomide or pomalidomide within a triplet or quadruplet regimen. Lenalidomide has a fixed place in therapy as the preferred agent for induction treatment of multiple myeloma.⁵² In the R/R setting, either lenalidomide or pomalidomide is a treatment option. Notably, results of sequencing trials support pomalidomide activity in patients who are lenalidomide refractory.^53,54 Some studies’ findings suggest that pomalidomide has greater binding affinity to cereblon and a greater capacity for protein degradation than lenalidomide,⁵⁵ although no comparative effectiveness superiority trials have been conducted to support clinical significance. Both agents share a similar AE profile; however, in trials of combination regimens containing daratumumab (Darzalex), dexamethasone, and an IMiD, any-grade diarrhea occurrence was greater with pomalidomide.⁵⁶

The future use of pomalidomide following the IRA’s pricing negotiations will likely be shaped by both economic and clinical considerations. As Medicare targets high-expenditure drugs such as pomalidomide for price negotiation, cost reductions may improve access but also influence the agents’ placement on formularies and in treatment algorithms. Although pomalidomide and lenalidomide share similar mechanisms, pomalidomide tends to have a different AE profile, which should be considered when selecting therapy. These factors must be weighed carefully as stakeholders adapt to a shifting reimbursement and therapeutic landscape.

Conclusions

Modern advancements have led to the development of multiple, comparable treatment options for cancer. Although clinical data should remain the primary determinant in drug selection, economic considerations and toxicity profiles also play a significant role in guiding therapy choices for individual patients. The IRA price negotiations may help alleviate the financial burden and play a significant role in dictating treatment. Future studies may be beneficial in assessing prescribing patterns starting with the first 2 cycles of negotiated pricing implementation. 

Author Affiliations: Atrium Health Levine Cancer (MKF, GE, AK, JLZ, DCM), Charlotte, NC.

Source of Funding: None.

Author Disclosures: Dr Fong is on an advisory board for an unbranded disease state website with Boehringer Ingelheim. Dr Karabinos is a shareholder in Bristol Myers Squibb. Dr Moore has been a consultant or paid advisory board member for Eli Lilly and Company, Genentech, Genmab, GSK, Incyte, and Sanofi. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MKF, DCM); acquisition of data (GE, AK, JLZ, DCM); analysis and interpretation of data (GE, AK, JLZ, DCM); drafting of the manuscript (MKF, GE, AK, JLZ, DCM); critical revision of the manuscript for important intellectual content (MKF, GE, AK, JLZ, DCM); administrative, technical, or logistic support (MKF); and supervision (MKF, DCM).

Address Correspondence to: Mei Ka Fong, PharmD, MS, BCOP, Atrium Health Levine Cancer, 1021 Morehead Medical Dr, Charlotte, NC 28204. Email: meika.fong@advocatehealth.org.

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