Laura Joszt, MA

's parent company, MJH Life Sciences, since 2011. She has an MA in business and economic reporting from New York University.

Financial toxicity in health care, particularly 

 care, has been a growing issue in the United States and the world that organizations are tackling across many formats, according to a panel at the Advanced Topics for Oncology Pharmacy Professionals Summit.

Patients are preoccupied with the financial burden of rising cancer care costs, Fumiko Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, explained by highlighting the results of a 2018 survey in which slightly more people were worried about the financial burden of their cancer care than of dying from cancer (57% vs 54%).

“So, this is something that is really a concern for our patients,” she said.

The issue of financial toxicity in cancer care has become a more popular research topic, with findings appearing in the “upper echelons of research,” 

Chino knows firsthand about the devastating effects of financial toxicity. After her husband received a cancer diagnosis and throughout his treatment, they 

 the overwhelming burden of bills for his cancer care. Even after he died, she was hounded by debt collectors for the cost of his treatment, “and it’s the reason why I went to medical school and the reason why I’m so passionate about the work.”

The common misconception is that financial toxicity is simply “high costs,” but it’s more than that. It is a patient-facing problem related to the cost of their care, and patients with cancer are more likely to face it. Even patients who have health insurance feel the burden and are left with debt.

Financial toxicity is driven by a few factors:

. In 1970, health expenditures were $74.6 billion, which climbed to $1.4 trillion in 2000 and $3.3 trillion in 2015, Chino pointed out, adding that it’s clearly “unsustainable.”

. While the median monthly price of new cancer treatments has sharply increased since 1995, patients' median monthly income has essentially stayed flat. In addition, many patients are underinsured, and the insurance they do have is not enough to pay for their treatment.

More people are being treated in the United States for cancer

. Sometimes this increased treatment is not for their benefit, Chino said. There is overdiagnosis and overtreatment of diseases that might not ultimately affect a patient’s mortality. Chino said she had an 80-year-old patient tell her that after catching her low-risk breast cancer, she had a double mastectomy, and it saved her life. “And in my mind, I’m like, ‘I’m not sure if that’s actually true,’” Chino admitted.

. New medical technology is very expensive but not always good quality or cost effective. The clinical benefit of some new medications is “stagnant or decreasing,” but the costs continue to rise. “Each new drug on the market is not adding a commensurate benefit for the cost,” Chino said.

Financial toxicity decreases quality of life (QOL), patient satisfaction with care, and even the quality of care, Chino said. While it may seem obvious that patients with a lot of financial problems are much less likely to rate their QOL as good, it’s also true that financial toxicity can shift a patient’s satisfaction with their care.

“Ultimately, costs erodes the quality of care that’s received,” Chino said. There becomes an adherence problem. A survey found that 22% of patients didn’t fill a prescription due to cost, 14% skipped doses to make medications last longer, and 5% skipped, took less, or didn’t fill their chemotherapy prescriptions.

When someone receives a cancer diagnosis, their risk of bankruptcy increases 2.65 times, and a bankruptcy after a cancer diagnosis is associated with a 79% increase in mortality risk. “Our treatments are causing quality-of-life decreases, quality-of-care decreases, huge financial burdens, and we’re actually killing some people,” she said.

Financial toxicity does not affect all patients equally, however. Research has shown that 1 in 20 Black or Latina women with early-stage breast cancer, which is completely treatable and curable, lost their home.

“Our treatments are making some people homeless,” Chino said. “That is untenable in the United States today.”

Financial navigator Daniel E. Sherman, MA, LPC, who is also a consultant with The NaVectis Group, followed Chino to discuss how to address financial toxicity. Treating financial toxicity needs to move to a place where it is part of the treatment plan for a patient instead of the patient just being referred to a financial counselor or social worker.

He has helped to implement a financial navigation program in more than 50 hospitals across the country and has seen that while hospitals usually have financial counselors, they don’t have clinical knowledge, don’t understand the diagnosis or the treatment plan, and their tools consist mostly of trying to get the patient on Medicaid or qualified for a hospital charity program.

The problem is that the majority of patients don’t quality, Sherman said. “What are we doing with the severely underinsured that doesn’t quality for charity or Medicaid?”

Financial advocacy that uses co-pay assistance and patient assistance program aren’t actually fixing the problem of financial toxicity—they’re just putting a band-aid on the problem, he said. These programs often focus on a treatment modality, but that doesn’t address all the other costs patients are faced with.

“We know that when patients come in, there are a lot of things that need to be put in place first before the interventions are done,” he said. For instance, they need a biopsy, surgery, to be hospitalized, etc.

Financial navigation looks at the issue differently and tries to educate patients on the extremely complicated health care system in the United States so they can move from being underinsured to more fully insured. Successful financial navigation services require a deep understanding of the health care system, which consists of:

Government safety net programs, like Medicaid and the Medicare Low-Income Subsidy

Health insurance policies, such as Medicare parts A, B, C, and D; the insurance marketplace; and commercial insurance

External assistance programs, such as patient assistance, co-pay assistance, premium assistance, basic needs assistance, and transportation

In addition, financial navigators need to have disease knowledge and treatment process, including progression, treatment modalities, treatment plans, length of treatment, and toxicities.

As a financial navigator, Sherman sees the patient on the day of their consult, because research has shown the patient is already coming into the system highly anxious about cost of care.

“I can count on 1 hand—maybe 4 times—when the patient said, ‘This is not a good time,’” Sherman said. “Most patients want to talk about this.”

He provided a case scenario of a 45-year-old single woman with 2 minor children making $58,000 annually who received an ovarian cancer diagnosis. She would need 6 months of chemotherapy, during which she cannot work. She has 3 months of short-term disability and is enrolled in a silver marketplace plan that costs $653 a month with a $6800 deductible and $17,100 maximum out-of-pocket (OOP) cost.

“What do you think that’s like?” Sherman asked. “Can you imagine the level of stress that this person is experiencing?”

He knows that marketplace insurance is based on a projected income, and her income was about to go to $0, so he called up and was able to get her monthly premium to $149 a month. In addition, her children went onto Medicaid. Her new maximum OOP costs was $2500 and her deductible was $400.

In addition, he found a foundation for ovarian cancer that paid health insurance premiums and he was able to bring it down to $0 a month, plus get her a little charity assistance on OOP.

“It’s fixing the insurance for the individual,” Sherman said. “That’s what financial navigation does.”

Finally, Ryan Haumschild, PharmD, MS, MBA, director of pharmaceutical services, Winship Cancer Institute, Emory University, explained that financial toxicity also plays a huge rule for institutions, not just patients. “There’s a ton we can do for the patients, but how do we focus on decreasing costs in the system?”

There are strategies to reduce expenses that have been around for a while, such as formulary management, medication use evaluations, inventory management and medication carrying costs, and manufacturer programs.

“Pathways, to me, are the future of care delivery,” he said. This is a shared decision-making framework that provides evidence-based care for similar outcomes and a predictable drug spend.

Emory treats patients in a large geographical area, and pathways were crucial to ensure patients were seeing different practices of care after different sites of care. For a patient, they were left with a challenging decision: travel the 50 miles to the academic medical center, where they had to find parking, navigate the building, and wait at a clinic that’s probable running behind schedule or go to a local practice that’s a lot easier for them to get to.

The center tried to “blow up the model” and “give the best outcomes possible regardless of where you’re treated,” Haumschild said.

He also highlighted the use of electronic medical records (EMRs), which can be used to drive care with a few features:

Order sets that drive best practice treatment protocols. 

EMRs allow Emory to build out pathways that align with the prior authorization and precertification team and links out to foundation support for patients, as well as steward patients along the way during their treatment.

The cost-effective therapy can be the primary treatment option. If there is an available biosimilar, then they can provider “great efficacy at a reduced cost,” Haumschild said.

. With documentation of process, when a lot of exceptions are requested, they can go reevaluate the pathway to determine if it’s the right one.

There are ways health systems can decrease cost without compromising clinical efficacy, such as through incorporating a pharmacoeconomic review when discussing formulary additions, understanding payer preferences, optimizing treatments when there are multiple indications, and considering the use of biosimilars.

Moving toward value-based care requires creating consistent practices; providing better or best outcomes to patients; incorporating evidence-based practices; considering the total cost of care, and not just the acquisition cost of the drug; providing innovative contracting; aligning prescribing with a strategic approach instead of one-off preference; and aligning the financial for patients and the organization to reduce spend across the health care system, Haumschild said.

Articles

Speakers at the Advanced Topics for Oncology Pharmacy Professionals Summit discussed financial toxicity in health care, how it particularly impacts patients with cancer, and how to address the issue with patients and the health system.

Addressing Financial Toxicity With Patients and Health Systems

 postremission treatment (PRT) and improve therapy stratification using dynamic measurable residual disease (

) in patients with intermediate-risk acute myeloid leukemia (AML), according to a study 

The researchers used the South China Hematology Alliance database to evaluate 549 patients between the ages of 14 and 60 years with intermediate-risk AML. Of these patients, 154 received chemotherapy, 116 received an autologous stem cell transplant (auto-SCT), and 279 received an allogeneic SCT (allo-SCT).

While most younger patients with AML can achieve complete remission (

) after induction chemotherapy, further PRT consisting of either a SCT or cytarabine-based consolidation chemotherapy is necessary to prevent a relapse, the authors explained. Although allo-SCT is more effective than auto-SCT when it comes to preventing relapse, it has a higher risk of transplant-related mortality.

“Currently, decisions for PRT depend mainly on risk stratification based on cytogenetics and molecular markers, but it remains controversial, particularly for patients with intermediate-risk AML,” they wrote.

MRD was assessed after induction therapy, each cycle of PRT, at 2-month intervals the first year, at 3-month intervals the second year, at 4-month intervals the third year, and finally half-year intervals during years 4 and 5 after PRT. The end point of the last follow up was August 31, 2020.

At the last follow up, 146 patients had relapsed, and the median time from first CR to relapse was 10.9 months. For patients receiving chemotherapy, the median time from first CR to relapse was 9.9 months; for patients receiving auto-SCT, 10.9 months; and for patients receiving allo-SCT, 13.0 months.

76 patients receiving chemotherapy relapsed; 58 received further treatment and 13 survived at the last follow-up

32 patients receiving auto-SCT relapsed; 26 received further treatment and 7 survived at last follow-up

38 patients receiving allo-SCT relapsed; 29 received salvage treatment and 6 survived at the last follow-up

The 5-year relapse rate was 49.4% (95% CI, 41.2%-57.0%) for patients on chemotherapy, 27.6% (95% CI, 19.8%-36.0%) for patients receiving auto-SCT, and 13.6% (95% CI, 9.9%-17.9%) for patients receiving allo-SCT. The 5-year cumulative incidence of transplant-related mortality was 1.3% (95% CI, 0.3%-4.2%) for chemotherapy, 3.4% (95% CI, 1.1%-8.0%) for auto-SCT, and 10.4% (95% CI, 7.2%-14.3%) for allo-SCT.

The 5-year overall survival (OS) and leukemia-free survival rates were higher for the SCT groups compared with the chemotherapy group. Both rates were comparable between the 2 SCT groups.

During subgroup analyses, patients were classified into 5 subgroups based on the dynamics of MRD after 1, 2, and 3 courses of chemotherapy:

Subgroup A was persistently MRD negative for all 3 courses. The 3 different PRT groups had comparable cumulative incidence of relapse, leukemia-free survival, and OS.

Subgroup B was persistently MRD positive after all 3 courses. The allo-SCT group had better leukemia-free survival and OS compared with the chemotherapy and auto-SCT groups, as well as a lower cumulative incidence of relapse.

Subgroup C was defined as being recurrent MRD positive after being MRD negative. The allo-SCT group had better leukemia-free survival and OS compared with the chemotherapy and auto-SCT groups, as well as a lower cumulative incidence of relapse.

Subgroup D was MRD negative after 2 courses of chemotherapy. Patients who received allo-SCT had significantly lower cumulative incidence of relapse, better leukemia-free survival, and better OS than patients in the other 2 groups.

Subgroup E was MRD negative after 3 courses of chemotherapy. Patients who received allo-SCT had a lower cumulative incidence of relapse and better leukemia-free survival, but a comparable OS compared with chemotherapy. Compared with auto-SCT, patients who received allo-SCT did not have a lower cumulative incidence of relapse, better leukemia-free survival, or difference in OS.

“Based on these results, we suggest that chemotherapy and auto-SCT might be preferable for patients who are persistently MRD negative, and allo-SCT should be recommended for patients who are persistently MRD positive and patients with recurrent MRD,” the authors concluded. “Auto-SCT prior to allo-SCT might be recommended for patients who are MRD negative after 2 cycles of chemotherapy. Allo-SCT might be preferable for patients who are MRD negative after 3 cycles of chemotherapy.”

Yu S, Fan Z, Ma L, et al. Association between measurable residual disease in patients with intermediate-risk acute myeloid leukemia and first remission, treatment, and outcomes.

Dynamic measurable residual disease (MRD) can be used to optimize postremission treatment for young patients with acute myeloid leukemia (AML).

Dynamic MRD Can Drive Clinical Decisions in AML

 disease (NALFD) is associated with decreased life expectancy, increased risks of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplant. Due to the lack of high-quality randomized controlled trials, it remains unclear at this time if patients with NAFLD might benefit from nutritional supplementation, according to a review 

The researchers performed a meta-analysis of randomized controlled trials to assess the benefits and harms of different nutritional supplements to treat NAFLD. They searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index‐Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021.

“Various medical treatments have been tried for treatment of NAFLD. However, no current evidence suggests that any of them work,” the authors explained. “Nutritional supplementation has the potential to decrease liver damage, but whether this occurs is currently unclear.”

The review included 202 trials with 14,200 participants, and 115 studies with 7732 participants were included in 1 or more comparisons. Only 19 trials were at low risk of bias.

The follow-up for the studies ranged from just 1 month to 28 months, and during the follow-up, clinical events related to NAFLD were sparse, likely a result of the short follow-up. As a result of the sparse data, the authors did not calculate effect estimates for mortality. The clinical outcomes that were of interest to the authors were mortality, liver cirrhosis, liver decompensation, liver transplantation, HCC, and liver‐related mortality.

“It takes follow‐up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population,” the authors explained.

The evidence around adverse events (AEs) was of very low certainty, but the authors did surmise that people taking polyunsaturated fatty acid (PUFA) may be more likely to experience an AE than patients not receiving an intervention (network meta‐analysis results: odds ratio [OR], 4.44, 95% credible intervals [CrI], 2.40-8.48; low‐certainty evidence; 4 trials, 203 participants; direct evidence: OR, 4.43, 95% CrI, 2.43-8.42).

There was not enough data for liver transplantation, liver decompensation, and HCC to perform outcome analysis.

The average age of patients ranged from 7 to 61 years in the studies, and the studies evaluated a variety of different treatments, including various vitamins and other nutritional supplements.

The authors highlighted the need for registry-based clinical trials that compare interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation to understand the impact of these interventions on indirect outcomes.

“The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non‐alcohol‐related fatty liver disease,” the authors concluded. “Accordingly, high‐quality randomized comparative clinical trials with adequate follow‐up are needed.”

Komolafe O, Buzzetti E, Linden A, et al. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. 

. 2021;7:CD013157. doi:10.1002/14651858.CD013157.pub2

The current available studies on nutritional supplementation in nonalcoholic fatty liver disease (NALFD) highlight the need for more high-quality randomized controlled trials.

Better Studies Needed on Nutritional Supplementation in NAFLD

Romyelocel-L, a treatment of ready-made human immune cells, can prevent infections in patients treated for 

 who have a weakened immune system, according to the results of a phase 2 trial 

The researchers evaluated a single infusion of romyelocel-L in immunocompromised patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. Romyelocel-L consists of immature, human-derived immune cells that work to replenish neutrophils and help fight or prevent infections.

“The current standard of care (cytarabine- and anthracycline-based induction regimens) for younger and fit older patients results in serious infections and an early mortality rate of 7%-11% despite administration of antimicrobials,” the authors explained.

The researchers conducted a multicenter, randomized, open-label, phase 2 study of romyelocel-L plus granulocyte colony-stimulating factor (G-CSF; treatment arm) versus G-CSF monotherapy (control arm) in patients receiving induction chemotherapy. The goal was to reduce chemotherapy-induced neutropenia. Patients in the treatment arm received an infusion of romyelocel-L on day 9, 10, or 11.

A total of 163 patients were enrolled from 21 US centers, and 120 of the patients were evaluable. In the treatment arm, 59 patients were evaluable, and in the control arm, 61 patients were evaluable.

Only 6.8% of patients in the treatment group experienced infections compared with 27.9% in the control group. Patients in the treatment group spent less time in the hospital (average of 25.5 days) compared with the control group (average of 28.7 days).

“This cell therapy has great potential to help AML patients by reducing their infections, length of hospital stays, use of antibiotics, and development of antibiotic resistance—leading to improved outcomes for them overall,” said lead author Pinkal Desai, MD, assistant professor of medicine in the Division of Hematology and Medical Oncology; the Charles, Lillian, and Betty Neuwirth Clinical Scholar in Oncology at Weill Cornell Medicine; and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Although the study met the end points showing lower incidence of infection, antibiotic use, and days of hospitalization in the treatment arm, there was no reduction in the mean duration of febrile episodes.

Patients receiving romyelocel-L had less frequent treatment-emergent significant adverse events (SAEs). Almost all of the SAEs (with the exception of 1) were considered not related to romyelocel-L. None of the patients on romyelocel-L had graft-versus-host disease or new-onset platelet refractoriness, nor did they have to be discontinued from the study because of an SAE or an AE.

“As infection remains the most common cause of morbidity and mortality in patients with AML, strategies to reduce the risk of infection are an unmet need,” the authors concluded. “These results provide the foundation for a phase 3 trial with the primary end point of reduction in infections during intensive induction chemotherapy for adults with AML.”

Desai PM, Brown J, Gill S, et al. Open-label phase II prospective, randomized, controlled study of romyelocel-L myeloid progenitor cells to reduce infection during induction chemotherapy for acute myeloid leukemia. 

. Published online June 22, 2021. doi:10.1200/JCO.20.01739

A new treatment using human immune cells can prevent infections in patients with leukemia who have a weakened immune system due to treatment for their disease.

Laura Joszt, MA

Articles

Addressing Financial Toxicity With Patients and Health Systems

Dynamic MRD Can Drive Clinical Decisions in AML

Better Studies Needed on Nutritional Supplementation in NAFLD

Therapy Can Prevent Infections in Immunocompromised Patients With Leukemia