Expanding Access to Chimeric Antigen Receptor T-Cell Therapies: Challenges and Opportunities.

Chimeric antigen receptor (CAR) T-cell therapy is a major advancement in the treatment of lymphoid malignancies, especially diffuse large B-cell lymphoma and acute lymphoblastic leukemia (ALL). Since the U.S. Food and Drug Administration (FDA) approval of two CAR T-cell therapies, axicabtagene ciloleucel and tisagenlecleucel, experience has highlighted various barriers to their broader access and use, including challenges related to manufacturing a patient-specific product, high costs and inadequate reimbursement, incomplete or nonsustained disease responses, and potential for causing life-threatening toxicities. Research on disparities, application, and practice of hematopoietic cell transplantation (HCT) can inform opportunities to address similar barriers to use of CAR T-cell therapies that are currently available as well as other cellular therapies that are expected to become available in the near future. To ensure optimal patient outcomes, these therapies should preferably be administered at centers that have experience and established quality processes and practices. We review opportunities for centers, manufacturers, payers, and policy makers to address barriers to care. We also provide a summary of available and alternative payments models for commercial CAR T-cell and other cellular therapies.

Comparison of Patient Age Groups in Transplantation for Myelodysplastic Syndrome: The Medicare Coverage With Evidence Development Study.

Importance: In 2010, the US Centers for Medicare & Medicaid Services (CMS) indicated that data regarding efficacy of allogeneic hematopoietic stem cell transplantation (HCT) in the CMS beneficiary population with myelodysplastic syndrome (MDS) were currently insufficient, but that coverage would be provided for patients enrolled in a clinical study that met its criteria for Coverage with Evidence Development (CED). Objective: The Center for International Bone Marrow Transplant Research (CIBMTR) submitted a study concept comparing the outcomes of patients aged 55 to 64 years vs aged 65 years or older who met those criteria, effectively providing coverage by CMS for HCT for MDS. Design, Setting, and Participants: Data on patients aged 65 years or older were prospectively collected and their outcomes compared with patients aged 55 to 64 years. Patients were enrolled in the study from December 15, 2010, to May 14, 2014. The results reported herein were analyzed as of September 4, 2017, with a median follow-up of 47 months. The study was conducted by the CIBMTR. It comprises a voluntary working group of more than 420 centers worldwide that contribute detailed data on allogeneic and autologous HCT and cellular therapies. Interventions: Patients with MDS received HCT according to institutional guidelines and preferences. Main Outcomes and Measures: The primary outcome was overall survival (OS); secondary outcomes included nonrelapse mortality (NRM), relapse-free survival, and acute and chronic graft vs host disease. Results: During the study period, 688 patients aged 65 years or older underwent HCT for MDS and were compared with 592 patients aged 55 to 64 years. Other than age, there were no differences in patient and disease characteristics between the groups. On univariate analysis, the 3-year NRM rate was 28% vs 25% for the 65 years or older group vs those aged 55 to 64 years, respectively. The 3-year OS was 37% vs 42% for the 65 years or older group vs the 55 to 64 years age group, respectively. On multivariable analysis after adjusting for excess risk of mortality in the older group, age group had no significant association with OS (HR, 1.09; 95% CI, 0.94-1.27; P = .23) or NRM (HR, 1.19; 95% CI, 0.93-1.52; P = .16). Conclusions and Relevance: Older patients with MDS undergoing HCT have similar OS compared with younger patients. Based on current data, we would recommend coverage of HCT for MDS by the CMS. Trial Registration: ClinicalTrials.gov identifier: NCT01166009.

Chimeric Antigen Receptor T-Cell Therapy.

Patients with relapsed or refractory (R/R) cancers have a poor prognosis and limited treatment options. The recent approval of 2 chimeric antigen receptor (CAR) autologous T-cell products for R/R B-cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma treatment is setting the stage for what is possible in other diseases. However, there are important factors that must be considered, including patient selection, toxicity management, and costs associated with CAR T-cell therapy. To begin to address these issues, NCCN organized a task force consisting of a multidisciplinary panel of experts in oncology, cancer center administration, and health policy, which met for the first time in March 2018. This report describes the current state of CAR T-cell therapy and future strategies that should be considered as the application of this novel immunotherapy expands and evolves.

Payment and Care for Hematopoietic Cell Transplantation Patients: Toward a Specialized Medical Home for Complex Care Patients.

Patient-centered medical home models are fundamental to the advanced alternative payment models defined in the Medicare Access and Children's Health Insurance Plan Reauthorization Act (MACRA). The patient-centered medical home is a model of healthcare delivery supported by alternative payment mechanisms and designed to promote coordinated medical care that is simultaneously patient-centric and population-oriented. This transformative care model requires shifting reimbursement to include a per-patient payment intended to cover services not previously reimbursed such as disease management over time. Payment is linked to quality measures, including proportion of care delivered according to predefined pathways and demonstrated impact on outcomes. Some medical homes also include opportunities for shared savings by reducing overall costs of care. Recent proposals have suggested expanding the medical home model to specialized populations with complex needs because primary care teams may not have the facilities or the requisite expertise for their unique needs. An example of a successful care model that may provide valuable lessons for those creating specialty medical home models already exists in many hematopoietic cell transplantation (HCT) centers that deliver multidisciplinary, coordinated, and highly specialized care. The integration of care delivery in HCT centers has been driven by the specialty care their patients require and by the payment methodology preferred by the commercial payers, which has included bundling of both inpatient and outpatient care in the peritransplant interval. Commercial payers identify qualified HCT centers based on accreditation status and comparative performance, enabled in part by center-level comparative performance data available within a national outcomes database mandated by the Stem Cell Therapeutic and Research Act of 2005. Standardization across centers has been facilitated via voluntary accreditation implemented by Foundation for the Accreditation of Cell Therapy. Payers have built on these community-established programs and use public outcomes and program accreditation as standards necessary for inclusion in specialty care networks and contracts. Although HCT centers have not been described as medical homes, most HCT providers have already developed the structures that address critical requirements of MACRA for medical homes.

Concise Review: The High Cost of High Tech Medicine: Planning Ahead for Market Access.

Cellular therapies and other regenerative medicines are emerging as potentially transformative additions to modern medicine, but likely at a staggering financial cost. Public health care systems' budgets are already strained by growing and aging populations, and many private insurer's budgets are equally stretched. The current systems that most payers employ to manage their cash flow are not structured to absorb a sudden onslaught of very expensive prescriptions for a large portion of their covered population. Despite this, developers of new regenerative medicines tend to focus on the demands of regulators, not payers, in order to be compliant throughout the clinical trials phases, and to develop a product that ultimately will be approvable. It is not advisable to assume that an approved product will automatically become a reimbursed product, as examples from current practice in hematopoietic stem cell transplantation in the U.S. demonstrate; similarly, in Europe numerous Advanced-therapy Medicinal Products achieved market authorization but failed to secure reimbursement (e.g., Glybera, Provenge, ChondroCelect, MACI). There are however strategies and approaches that developers can employ throughout clinical development, in order to generate clinical and health economic data which will be necessary to demonstrate the value proposition of the new product and help ensure market access for patients; furthermore, performance based managed entry agreements coupled with post-launch evidence generation can help overcome challenges around product uncertainty at launch and reduce market access delays. Stem Cells Translational Medicine 2017;6:1723-1729.

Challenges around Access to and Cost of Life-Saving Medications after Allogeneic Hematopoietic Cell Transplantation for Medicare Patients.

Hematopoietic cell transplantation (HCT) is an expensive, medically complicated, and potentially life-threatening therapy for multiple hematologic and nonhematologic disorders with a prolonged trajectory of recovery. Similar to financial issues in other cancer treatments, adverse financial consequences of HCT are emerging as an important issue and may be associated with poor quality of life and increased distress in HCT survivors. Prescription medicine coverage for HCT for Medicare and some Medicaid beneficiaries, especially in the long-term, remains suboptimal because of inadequate payer formularies or prohibitive copays. With an increasing number of older patients undergoing HCT and improvement in the overall survival after HCT, the problem of financial burden faced by Medicare beneficiaries with fixed incomes is going to worsen. In this article, we describe the typical financial burden borne by HCT recipients based on estimated copayment amounts attached to the categories of key medications as elucidated through 2 case studies. We also suggest some possible solutions for consideration to help these patients and families get through the HCT by minimizing the financial burden from essential medications needed during the post-HCT period.

Healthcare Costs and Utilization for Patients Age 50 to 64 Years with Acute Myeloid Leukemia Treated with Chemotherapy or with Chemotherapy and Allogeneic Hematopoietic Cell Transplantation.

The primary aim of this study was to describe healthcare costs and utilization during the first year after a diagnosis of acute myeloid leukemia (AML) for privately insured non-Medicare patients in the United States aged 50 to 64 years who were treated with either chemotherapy or chemotherapy and allogeneic hematopoietic cell transplantation (alloHCT). MarketScan (Truven Health Analytics) adjudicated total payments for inpatient, outpatient, and prescription drug claims from 2007 to 2011 were used to estimate costs from the health system perspective. Stabilized inverse propensity score weights were constructed using logistic regression to account for differential selection of alloHCT over chemotherapy. Weighted generalized linear models adjusted costs and utilization (hospitalizations, inpatient days, and outpatient visit-days) for differences in age, sex, diagnosis year, region, insurance plan type, Elixhauser Comorbidity Index), and 60-day prediagnosis costs. Because mortality data were not available, models could not be adjusted for survival times. Among 29,915 patients with a primary diagnosis of AML, 985 patients met inclusion criteria (774 [79%] receiving chemotherapy alone and 211 [21%] alloHCT). Adjusted mean 1-year costs were $280,788 for chemotherapy and $544,178 for alloHCT. Patients receiving chemotherapy alone had a mean of 4 hospitalizations, 52.9 inpatient days, and 52.4 outpatient visits in the year after AML diagnosis; patients receiving alloHCT had 5 hospitalizations, 92.5 inpatient days, and 74.5 outpatient visits. Treating AML in the first year after diagnosis incurs substantial healthcare costs and utilization with chemotherapy alone and with alloHCT. Our analysis informs healthcare providers, policymakers, and payers so they can better understand treatment costs and utilization for privately insured patients aged 50 to 64 with AML.

Administrative Claims Data for Economic Analyses in Hematopoietic Cell Transplantation: Challenges and Opportunities.

There is an increasing need for the development of approaches to measure quality, costs, and resource utilization patterns among allogeneic hematopoietic cell transplantation (HCT) patients. Administrative claims data provide an opportunity to examine service utilization and costs, particularly from the payer's perspective. However, because administrative claims data are primarily designed for reimbursement purposes, challenges arise when using it for research. We use a case study with data derived from the 2007 to 2011 Truven Health MarketScan Research database to discuss opportunities and challenges for the use of administrative claims data to examine the costs and service utilization of allogeneic HCT and chemotherapy alone for patients with acute myeloid leukemia (AML). Starting with a cohort of 29,915 potentially eligible patients with a diagnosis of AML, we were able to identify 211 patients treated with HCT and 774 treated with chemotherapy alone where we were sufficiently confident of the diagnosis and treatment path to allow analysis. Administrative claims data provide an avenue to meet the need for health care costs, resource utilization, and outcome information. However, when using these data, a balance between clinical knowledge and applied methods is critical to identifying a valid study cohort and accurate measures of costs and resource utilization.

Goals for Pay for Performance in Hematopoietic Cell Transplantation: A Primer.

Bundled payments for hematopoietic cell transplantation (HCT) have long been accepted by both commercial health insurance providers and transplant centers, effectively outpacing the use of this payment model elsewhere in health care. As with the rest of health care, interest in payment and health delivery reform has created demand for transplant providers to address value by incorporating quality metrics and strategic changes in network design The complexity of evaluating performance in HCT complicates the goal of rewarding providers for better performance and penalizing poor results. We provide an introduction to value-based purchasing and address potential considerations in the adoption of incentives to improve quality of care in HCT.

Guidelines for defining and implementing standard episode of care for hematopoietic stem cell transplantation within the context of clinical trials.

The Patient Protection and Affordable Care Act requires that health care insurers cover routine patient costs associated with participating in clinical trials for cancer and other life-threatening diseases. There is a need to better define routine costs within the context of hematopoietic stem cell transplantation (HSCT) clinical trials. This white paper presents guidance on behalf of the American Society for Blood and Marrow Transplantation for defining a standard HSCT episode and delineates components that may be considered as routine patient costs versus research costs. The guidelines will assist investigators, trial sponsors, and transplantation centers in planning for clinical trials that are conducted as a part of the HSCT episode and will inform payers who provide coverage for transplantation.

Variation in medicaid coverage for hematopoietic cell transplantation.

PURPOSE: Variation in Medicaid policies among states may lead to differences in coverage for complex treatments. This article uses hematopoietic cell transplantation (HCT), an established treatment for patients with hematologic cancers, as a case study to highlight state variation in Medicaid coverage of complex oncology treatments. METHODS: Information on HCT coverage benefits for 2012 was collected from state Medicaid Web sites and was compared with recommended HCT benefits developed by multiple stakeholders. Coverage was reviewed for five categories: one, transplantation procedure; two, donor search; three, prescriptions; four, clinical trials; and five, patient food, lodging, and transportation. Coverage was coded on a three-point scale for each category for each state. States were ranked by the number of variables for which they met recommended benefits criteria (maximum rank score, 5). RESULTS: Detailed information on Medicaid coverage was available for 47 states. No state provided the recommended coverage benefits in all five categories. Prescription coverage most often met the recommended criteria, whereas only a small number of states provided clinical trial coverage for HCT. There was substantial variation in Medicaid coverage for HCT by state. CONCLUSION: Findings highlight substantial variation in Medicaid coverage for HCT by state, which may increase disparities in access for already medically underserved populations.

Impact of the Affordable Care Act on stem cell transplantation.

The Patient Protection and Affordable Care Act, signed into law in 2010, will have a wide-reaching impact on the health care system in the United States when it is fully implemented in 2014. Patients will see increased access to care coupled with new insurance coverage protections as well as a minimum set of benefits mandated in each state known as essential health benefits. Providers are likely to see new forms of payment reform, particularly in the Medicare program, and narrower commercial provider networks. In addition, the composition of the health insurance market will broaden with the introduction of health insurance exchanges and expanded Medicaid populations in many states. Furthermore, the Patient Protection and Affordable Care Act calls for quality initiatives such as comparative effectiveness research to increase effective, appropriate and high-value care. This paper will review the main provisions of the Patient Protection and Affordable Care Act with specific attention to their impact on the field of Stem Cell Transplantation.

Standardization of terminology for episodes of hematopoietic stem cell patient transplant care.

The nomenclature describing hematopoietic stem cell transplantation has evolved, adding precision and definition in research and regulation. The lack of coordination and standardization in terminology has left some gaps in the definition of episodes of clinical care. These voids have caused particular problems in contracting for payment and billing for services rendered. The purpose of this report is to propose definitions for cell products, cell infusions, and transplantation episodes.