ASH 2019: Real-World Evidence and Cost of Care

January 21, 2020

Reviews of apixaban in active cancer, Medicare costs after CAR T-cell therapy, and the need for financial assistance for novel therapies.

Apixaban Is Linked to Large Reductions in Major Bleeding, Recurrent VTE in Active Cancer

Patients with cancer who took apixaban to prevent blood clots had a 37% reduction in major bleeding (MB) and a 39% reduction in recurrent venous thromboembolism (VTE) compared with those taking low-molecular weight heparin (LMWH), according to data presented on December 7, 2019, at the 61st American Society of Hematology Annual Meeting & Exposition in Orlando, Florida. Apixaban also had large reductions in VTE (32%) relative to warfarin.1

A subgroup analysis presented alongside the main study found that apixaban’s benefi ts relative to LMWH held up across different types of cancer regardless of the risk level they present for VTE.2 Apixaban is sold as Eliquis by Bristol-Myers Squibb/Pfizer. Patients with active cancer—for this study, defined as cancer diagnosis or treatment in the 6 months before or 30 days after a VTE diagnosis—have a 4 to 7 times greater risk of developing VTE.

To gain more real-world evidence on the eff ectiveness and safety of LMWH compared with vitamin K antagonists, which emerged in the last decade as a treatment of VTE, and non-VKA anticoagulants, a team of researchers led by Alexander T. Cohen, MBBS, MSc, MD, of King’s College, London, evaluated the effi cacy of apixaban, LMWH, and warfarin among patients with active cancer.

The investigators examined 3 groups of patients who started treatment within 30 days of their first VTE: 3393 apixaban users, 6108 LMWH users, and 4585 warfarin users. The mean ages were 65, 64, and 64 years, respectively. To evaluate rates of MB, clinically relevant non-MB (CRNMB), and recurrent VTE, the patients were followed to the earliest of 1 of 6 time points: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months.1

The following results were reported:

• Apixaban had lower risks of MB, CRNMB, and recurrent VTE compared with LMWH, with a hazard ratio (HR) of 0.63 (95% CI, 0.47-0.86; P = .003) for MB, an HR of 0.81 (95% CI, 0.70-0.94; P = .006) for CRNMB, and an HR of 0.61 for recurrent VTE (95% CI, 0.47-0.81; P = .001).

• Apixaban had lower rates of recurrent VTE and modest reductions of MB and CRNMB compared with warfarin, with an HR of 0.68 (95% CI, 0.52-0.90; P = .007) for recurrent VTE, an HR of 0.73 (95% CI, 0.53-1.0; P = 0.51) for MB, and an HR of 0.89 (95% CI, 0.77-1.04; P = 0.145) for CRNM.

“Real-world evidence analyses such as this have the potential to provide additional insights into complex patient populations such as those with VTE and active cancer,” Cohen said in a statement.3 “Results from these analyses are a welcomed addition to the growing body of data around recurrent VTE in patients with active cancer.”

In the second presentation, results from the subgroup analysis examined how apixaban aff ected recurrent VTE, MB, and CRNMB risk across diff erent cancer types relative to warfarin and LMWN. Hematologic cancer, as well as those of the brain, pancreas, stomach, liver, lungs, and kidneys, are associated with a higher risk of VTE. Researchers used the Khorana risk score based on cancer type, blood counts, and body mass index to evaluate risk level and assess the safety of each therapy based on cancer type. Patients were categorized as having a very high risk of VTE, high risk of VTE, or other.

Results from the same real-world data set as the fi rst abstract showed that those taking apixaban had a lower risk of recurrent VTE compared with warfarin and a lower risk of MB, CRNMB, and recurrent VTE compared with LMWH, consistent with the overall results. Researchers called for more studies to evaluate the role of anticoagulants in high-risk subgroups of patients with cancer who have VTE.2

Besides the risk of VTE, real-world evidence can be evaluated for other factors. Asked by Evidence-Based Oncology™ if the patient data could be evaluated to see whether those with comorbidities had diff erent responses, Danny Wiederker, HEOR team lead at Pfi zer, said in an email, “Comorbidities are always an important consideration in real-world evidence, given some may be important confounders that impact both the treatment decision and the outcomes of interest. That’s why the Pfizer/BMS Alliance leverages the best research practices recommended by organizations like the International Society of Pharmacoeconomics and Outcomes Research that look to adjust for both comorbidities and patient factors, like age, gender, etc, that may impact outcomes.”

He said the study being presented is the inverse probability of treatment weighting to adjust for confounding while including the broadest possible patient population.

“Our approach generally is to start with the broad population and then drill down into subgroups as we are also highly interested in better understanding in which patient populations there is even more unmet need and more opportunity to improve outcomes,” Wiederker said. “We have conducted the first subgroup analysis presented as the second oral presentation stratifying based on the risk of recurrent VTE level, but we also have interest in other subgroups and are exploring opportunities for additional analyses.”


1. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH, and warfarin among venous thromboembolism patients with active cancer: a retrospective analysis using four US claims databases. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 326. Accessed December 7, 2019.

2. Cohen AT, Keshishian A, Lee T, et al. Safety and effectiveness of apixaban, LMWH and warfarin among venous thromboembolism (VTE) patients with active cancer: a subgroup analysis of VOTE risk scale. Presented at: 61 American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 327. Accessed December 7, 2019.

3. Findings released from real-world data analysis of Eliquis (apixaban) for the treatment of venous thromboembolism in patients with active cancer [press release]. Princeton, NJ, and New York, NY: Businesswire. Accessed December 7, 2019.

Real-World Results Show Medicare Costs Drop After Completion of CAR T-Cell Therapy

Most Medicare patients treated with chimeric antigen receptor (CAR) T-cell therapies in the first year after FDA approval for diff use large B-cell lymphoma fared well after the procedure, according to an Avalere Health study presented at the 61stŸAmerican Society of Hematology Annual Meeting and Exposition in Orlando, Florida.

More than half of the patients treated with this expensive revolutionary therapy had comorbidities common in seniors, such as heart disease or renal problems, that might have kept them out of clinical trials. But 6 months after treatment, hospital stays dropped 17% from pretreatment levels. And healthcare costs 6 months after CAR T-cell therapy, based on Medicare Part A and B, were 39% lower than they were in the 6 months before treatment, said lead study author Karl M. Kilgore, PhD, who shared results from 207 patients in a press briefi ng on December 7, 2019. The study is the first claims analysis from Medicare patients who received CAR T-cell therapy in the year after October 1, 2017.1 The FDA approved Novartis’ tisagenlecleucel (Kymriah) in August, followed by Gilead’s axicabtagene ciloleucel (Yescarta), in October 2017. Both are approved to treat adults with relapsed or refractory large B-cell lymphoma.2

Medicare patients in the Avalere study were more than a decade older than the median age of patients in clinical trials, yet many had good outcomes. “Our findings off er evidence that older patients with multiple comorbidities can be treated successfully with CAR T,” he said in a statement.3 “While we don’t know the long-term outcomes yet, nearly three-quarters of the patients were still alive 6 months posttreatment.”

Kilgore said this is the fi rst analysis to use real-world evidence—in this case, Medicare claims—to examine how CAR T-cell therapy works in older patients with other health issues. Although the Avalere study found a signifi cant decline in both healthcare utilization and cost, Kilgore was clear that this “is not a cost-effectiveness study,” meaning it was not designed to evaluate the healthcare savings seen after treatment against the cost and benefits of treatment itself. CAR T-cell therapy in this indication costs $373,000 just for the specially engineered therapy manufactured from a patient’s own cells. Administration costs, including the cost of treating adverse events, can easily drive the total price tag closer to $1 million.

Medicare and academic centers that off er CAR T-cell therapy have battled over reimbursement rates for more than a year, and while payment is set to rise in 2020, a commentary in the Journal of Clinical Oncology in November estimated that centers lose $300,000 on every Medicare patient they treat.4

Highlights from the Avalere study showed1:

• The median age of the Medicare patients was 71, compared with 56 to 58 years of age in clinical trials, and 51% of individuals in the Medicare group had 1 or more

chronic conditions.

• Results after 177 patients showed the drop in per-patient per-month healthcare utilization costs in Medicare Part A and B fell from $9749 in the period 6 months before CAR T-cell therapy to $7121 in the 6 months after therapy. Kilgore said in an interview with Evidence-Based Oncology™ that Part D data had not been released in time for the American Society of Hematology meeting and would be analyzed separately.

• Six months after treatment, emergency department visits dropped by 45%, and the number of patients visiting the emergency department dropped by one-third.

• The study shed light on the healthcare needs of Medicare patients receiving CAR T-cell therapy—the average hospital stay for the procedure is 17 days. Less than half needed time in the intensive care unit; those that did stayed 13 days.

Kilgore noted that reimbursement methods to hospitals performing CAR T-cell treatment vary, with some subject to the acute inpatient prospective payment system rule, while others are exempt.5 The Avalere study found that the Centers for Medicare & Medicaid Services, on average, is reimbursing under the inpatient prospective payment system about $422,000, compared with $467,000 in the outpatient setting.3

Joseph Alvarnas, MD, an oncologist/hematologist who serves as vice president of government affairs and senior medical director for employer strategy for City of Hope in Duarte, California, and is editor-in-chief of Evidence-Based Oncology™, said that while the Avalere analysis is not a cost-eff ectiveness study or a comparative eff ectiveness model, “These data add to other data sets that continue to validate the idea that there is a real value proposition for these therapeutics, that provides a path toward developing an economically sustainable model for treating this population of patients.”

The authors acknowledge that the Medicare patient sample remains small and that it may not represent a broader patient population. Kilgore has received research funding from Kite Pharma, which developed the CAR T-cell product that Gilead acquired and launched Avalere’s results were part of a set of abstracts that highlighted results involving disparities in care. Other results include:

• A study of 1040 patients with acute myeloid leukemia (AML), presented by Abby Statler, PhD, MPH, of Cleveland Clinic, found that issues with renal function appear to be a barrier to enrollment in clinical trials for African Americans. However, there is no association between clinically insignificant renal lab values and response to treatment or overall survival (OS), so the study recommends adjusting trial eligibility criteria to reduce racial disparities in enrollment.6

• Lena E. Winestone, MD, MSHP, of the University of California, San Francisco, presented data that show children with AML from middle- and high-income areas

experience a 25% lower mortality risk compared with those from low-income areas (OS, crude hazard ratio [HR], 0.74; 95% CI, 0.62-0.89; adjusted HR, 0.79; 95% CI, 0.63-0.99). Clinical trial data were matched with zip-code data as a proxy for income, and the authors of the study concluded that “zip-code—based low socioeconomic status is an independent risk factor for mortality in pediatric AML.”7

• Anita D’Souza, MD, MS, of the Medical College of Wisconsin at Milwaukee, presented a large study of autologous hematopoietic cell transplantation in older adults with multiple myeloma (at least 70 years of age) and found that these older patients can safely undergo the transplant procedure with the same benefi ts that are seen in younger patients. Adjusted results show that compared with patients aged 60 to 69 years, those 70 years of age or older had similar nonrelapse mortality, with an HR of 1.3 (95% CI, 11.7; P = .06); progression-free survival; HR, 1.06 (95% CI 11.2, P = .2); and OS, with an HR of 1.2 (95% CI, 11.4; P = .02).8


1. Kilgore K, Mohammadi I, Schroeder A, et al. Medicare patients receiving chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma: a first real-world look at patient characteristics, healthcare utilization and costs. Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10,

2019; Orlando, FL. Abstract 793. Accessed December 7, 2019.

2. Rosenberg J. FDA approves CAR T-cell treatment Kymriah for adult B cell lymphoma. The American Journal of Managed Care® website. Published May 2, 2018. Accessed December 10, 2019.

3. Studies offer mix of hope and challenges in addressing cancer care disparities [press release]. Orlando, FL: American Society of Hematology; December 7, 2019. Accessed December 7, 2019.

4. Manz CR, Porter DL, Bekelman JE, et al. Innovation and access at the mercy of payment policy: the future of chimeric antigen receptor therapies [published November 1, 2019]. J Clin Oncol. doi:10.1200/JCO.19.01691.

5. Center for Medicare and Medicaid Services. Acute inpatient PPS.

index. Updated November 15, 2019. Accessed December 7, 2019.

6. Statler A, Hobbs BP, Radivoyevitch T, et al. Are racial disparities in acute myeloid leukemia clinical trial enrollment associated with comorbidities and/or organ dysfunction? Presented at: 61stƒAmerican Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 381. Accessed December 7, 2019.

7. Whitestone LE, Getz KD, Bona KO, et al. Areabased socioeconomic disparities in survival of children with newly diagnosed acute myeloid leukemia: a report from the Children’s Oncology Group. Presented at: 61stƒAmerican Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 703. Accessed December 7, 2019.

8. Munshi PN, Hari P, Vesole DH, et al. Breaking the glass ceiling of age in transplant in multiple myeloma. Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 782. Accessed December 7, 2019.

Most Patients With Medicare Need Additional Financial Assistance to Get Novel Oral Therapies

It's no surprise that oral novel therapeutics (ONTs) used to treat hematologic malignancies are expensive. What is surprising is that most patients receiving Medicare require additional fi nancial assistance to help pay for these therapies each month, according to data presented on December 7, 2019, at the 61st American Society of Hematology Annual Meeting and Exposition in Orlando, Florida.

Karmanos Cancer Institute, in Detroit, Michigan, established a specialty pharmacy to help alleviate the financial burden many patients face when paying for their ONTs. The pharmacy helps streamline the often frustrating and complex process of obtaining prior authorization (PA) and determining patient payment obligation.

Federal regulations prohibit Medicare beneficiaries from using copay cards to decrease their out-of-pocket costs because CMS believes that doing so will drive up overall costs for insurers. Karmanos then goes one step further on behalf of patients, automatically applying for fi nancial assistance when necessary, in the form of copay cards and foundation grant funding, before determining what a patient will ultimately have to pay and when their drugs will be delivered.

Hoping to establish patterns of cost and the need for fi nancial assistance since the specialty pharmacy was established, first author Erlene K. Seymour, MD, and her team used a retrospective data review from March 2018 through May 2019. During this time, the prescription claims totaled over $2 million. Data were gathered on the following: drug prescribed, type of insurance (Medicare, Medicaid, private), insurer cost, final patient cost sharing, costs covered by foundation grant assistance or copay cards (if needed), and the number of days between written prescription and (1) PA and (2) drug delivery to patient (see Table).1

Overall, 35% of the patients needed help with payment, most of which was achieved through foundation grants versus copay cards (26% vs 9%). Medicare accounted for half of all reimbursement; 40% of these patients needed foundation grant assistance, and 19% ended up with high copays of $100 or more. Fifty-two percent of patients had Medicare; 33%, private coverage; and 17%, Medicaid. From most to least costs covered, Medicare topped the list by paying half, followed by foundation grant assistance, the patients themselves, and copay cards. Also, neither insurance type nor grant need factored into time needed for PA or drug delivery at 1 and 7 days, respectively.

“Of the $2 million in total drug costs, 4% was total patient copayments, which presented as high copays for many patients. Thirty-six percent of these patients received fi nancial assistance, mostly through foundation grants,” Seymour said in an email to Evidence-Based Oncology™. “Karmanos Specialty Pharmacy implemented an efficient process of applying for fi nancial assistance, which decreased total patient cost by 79%. However, the fact that so many required assistance or continued

to pay high copays emphasizes the need to cap these costs for our patients.”


1. Seymour EK, Daniel L, Pointer E, Smith ST, Schiffer CA. High dependence on Medicare and foundation grant assistance among patients with hematologic

malignancies receiving novel oral therapeutics. Presented at: 61st American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019;

Orlando, Florida. Abstract 64.