For Transplants, Is Age Just a Number?

Growing Demand, Little Coverage for Older Patients in Need of a Bone Marrow Transplant

Many of the hematologic conditions that can be treated with blood and bone marrow transplants – leukemia, lymphoma, myeloma – are considered diseases of older individuals, with a median age at diagnosis ranging from 60 to over 70 years. Unfortunately, many of these individuals, specifically those who are Medicare beneficiaries, struggle to obtain insurance coverage for these potentially life-saving, but expensive, procedures.

“In many of the landmark transplant procedures in the late 1970s, the upper age limit was only 30 years old,” Sergio A. Giralt, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York, told ASH Clinical News. “Even when I started transplanting in 1989, we couldn’t transplant people older than 50 [years] because they could not tolerate high-dose chemotherapy and radiation.”

It was only recently in the history of bone marrow transplantation that techniques have advanced to allow a wider variety of patients to safely and successfully undergo the procedure, including older adults. And, even more recently, improvements in donor-matching and conditioning regimens have led to older patients experiencing outcomes similar to those of younger patients.

Commercial payers have coverage policies for transplantation for as many as 70 different indications, but Medicare, the single largest payer for health insurance in the United States, only has National Coverage Determinations (NCD) for allogeneic hematopoietic cell transplants (alloHCTs) for four indications (leukemia, aplastic anemia, severe combined immunodeficiency disease, and Wiskott–Aldrich syndrome) and limited coverage for myelodysplastic syndromes (MDS) under a Coverage with Evidence Development (CED) ruling.

“This means that, at best, Medicare is covering 10 percent of indications for allogeneic transplant,” according to Linda J. Burns, MD, vice president and medical director of health services research at the National Marrow Donor Program/Be The Match, and a member of the Center for International Blood and Marrow Transplant Research (CIBMTR) Executive Committee.

ASH Clinical News recently spoke with several transplant experts and others in health care about some of the challenges related to obtaining insurance coverage for bone marrow transplants in older adults and what can be done to begin to advocate for change.

Expanding Eligibility

There is no doubt that older patients (>60 years) are increasingly undergoing autologous hematopoietic cell transplantation (AHCT) and alloHCT to treat their hematologic diseases. Recent data from CIBMTR estimated that, between 2007 and 2013, 44 percent of AHCT recipients and 22 percent of alloHCT recipients were older than 60 years.1

One of the greatest advances in the field that has helped facilitate broader use of transplantation for older adults is the ability to identify the best donor for each patient, according to Dr. Burns. The use of human leukocyte antigen (HLA)-matched unrelated donors considerably increased the likelihood that patients could undergo transplantation if they do not have a suitable family member donor. According to data from CIBMTR, the number of unrelated donor transplants surpassed the number of transplants from related donors in 2006, and the gap between the two approaches widens every year.1

Secondly, the development of reduced-intensity conditioning regimens, which use lower doses of chemotherapy and radiation, have decreased early transplant-related complications, toxicity, and mortality and opened the door to offering transplantation to older patients or those with certain preexisting comorbidities.

Finally, supportive care for patients throughout the transplant process has improved, Dr. Burns noted. “For example, there are serious infections – cytomegalovirus, for example – that may increase a patient’s risk of death,” Dr. Burns said. “When I first entered the transplant field, we had hardly any medications for patients with cytomegalovirus infections, resulting in more than 80 to 90 percent lethality. Since then, several antiviral drugs have been developed that have dramatically decreased the chance of patients dying.”

These developments, plus the medical community’s improved understanding of the appropriate timing of transplant, has changed the landscape of hematopoietic cell transplants for hematologic conditions.

Slow to Adapt

Despite these advances in transplantation, the Centers for Medicare and Medicaid Services (CMS) has been slow to expand coverage of hematopoietic cell transplant. For example, it was only in 2010 that CMS issued a decision memo stating that there was not sufficient evidence to demonstrate that the use of transplant for MDS was “reasonable and necessary,” and instead approved coverage for the procedure under its CED program.2 This meant that transplant for MDS was covered by Medicare only for beneficiaries participating in an approved clinical trial.

“This is a great mechanism for CMS to help us provide transplant to older individuals with this indication, but the issue is that we are wasting resources to perform studies where the sole intention is to provide access to transplant,” Navneet Majhail, MD, MS, director of the Blood & Marrow Transplant Program at Cleveland Clinic, told ASH Clinical News. “We have to do clinical studies for these complex diseases, which can take five to 10 years to accrue enough participants, and we have to deal with the regulatory burden just to provide data to confirm efficacy – which has been demonstrated in other studies.”

For example, a review of CIBMTR data from 1995 to 2010 looking at 1,080 patients with acute myeloid leukemia (AML) or MDS who underwent reduced-intensity transplantation, found that there was no significant difference in two-year survival rates based on patient age, including those >65 years.3

Stephanie Farnia, MPH, director of payer policy with the National Marrow Donor Program/Be The Match, compared the use of CED for transplant coverage with the concept of the chicken and the egg.

“Because transplants were not explicitly covered, they were not being conducted in people older than 65 [years] and, therefore, there was not a lot of evidence about transplant in this patient population,” Ms. Farnia said. “Therefore, Medicare said that there was no specific evidence in this age group and mandated a CED.”

Then, in January, CMS issued a decision memo announcing that it would modify its existing NCD Manual to expand transplant to three additional medical conditions: sickle cell disease (SCD), myelofibrosis, and multiple myeloma (MM).4 (For a closer look at this decision, see our article, “CMS Expands Coverage for Hematopoietic Cell Transplantation: Proceed with Cautious Optimism” from our May 2016 issue.)

There are eligibility restrictions for patients within each indication (based on their risk level and disease severity), and all three new indications will be covered under the CED paradigm. Although the CED ruling is in progress, the road to full coverage is long, Ms. Farnia said.

“We have four indications under CED,” she noted, adding that “the first clinical trial for MDS, opened in 2010, is being conducted by CIBMTR, and is still accumulating data. In June 2016, CMS approved the BMT CTN 1503 trial for beneficiaries with SCD, and it began patient accrual in September 2016.”

According to Ms. Farnia, while this study was already under development when CMS issued the CED coverage, it was adapted for this purpose. However, it is a small study in which only about 60 patients with SCD will receive transplants. CED-eligible studies for multiple myeloma (MM) and myelofibrosis are still in development.

“Later this year, we are hoping to ask CMS to go through the national coverage analysis and make a final decision, and that is a year-long process,” said Ms. Farnia, adding that it takes anywhere from five to 10 years to get an indication to move through CED to full coverage.

Crunching the Numbers

For conditions and procedures that are not explicitly covered by an NCD or CED, coverage determinations are made by Medicare Administrative Contractors (MACs) who create their own local coverage determination policies to decide if a condition or treatment is covered under Medicare.

“The MACs are not allowed to offer prior authorization, and any coverage granted is usually retroactive,” Dr. Majhail explained. “You do a procedure, submit a claim, and the MACs decide whether or not they are going to pay for that service. In that setting, it becomes problematic for an institution to take on the financial risk of doing an expensive procedure like transplant without the confidence that the procedure will be covered and paid for.”

Even for the conditions that receive Medicare coverage, hospitals and patients are often left dealing with expensive bills.

“If a patient is referred for transplant we do a benefit check upfront to see if the transplant will be covered at our institution,” said Dr. Majhail. “If they have a commercial payer and we are given prior authorization, we are often paid in phases.”

Patients who have commercial insurance typically receive more comprehensive coverage for transplant that includes services received during all phases of the transplant, from preparative regimen days (“minus days”), to the transplant procedures (“day zero”), to post-transplant recovery (days 30-60+).

“Commercial contracts are confidential, and rightfully so, but most use a case rate that covers a set number of days or a full transplant episode,” Ms. Farnia said. “I would estimate that reimbursement on the commercial side is typically somewhere between $200,000 and $400,000 for the transplant episode.”

If a patient gets sick and is admitted to the intensive care unit for a complication related to the transplant or conditioning regimen, institutions can ask for additional reimbursement. Once a patient is discharged, commercial payers continue to cover that patient’s follow-up care.

For its covered indications, Medicare also pays per episode, but only for the inpatient stay, Dr. Majhail explained. “[Compared with Medicare,] commercial payers pay at a rate that is closer to the actual costs that we incur,” he said.

In 2015, the current Inpatient Payment Base for transplant was:

  • $64,432 for alloHCT (diagnosis-related group [DRG] 014)
  • $34,477 for AHCT with major complication or comorbidity or a complication or comorbidity (MCC/CC; DRG 015)
  • $24,402 for AHCT without MCC/CC (DRG 017)

These reimbursement rates are “not even close to covering what it costs for the inpatient stay,” Dr. Majhail said. “They do not reflect the actual costs for providing treatment to these patients.”

According to Dr. Giralt, performing an allo-HCT for Medicare patients is, on an economic level, a money-losing proposition – particularly because Medicare coverage does not include any “minus days” and does not accurately cover the cost of obtaining the donor marrow. “CMS covers the procurement of all transplant organs except for bone marrow,” he noted.

That means that a hospital will spend a good portion of time “in the red” before an individual even checks into the hospital, Ms. Farnia added.

“If a patient is getting marrow from an unrelated donor, the hospital is already incurring somewhere between $30,000 to $50,000 to identify donor cells, get the cells, and get them ready for transplant,” she explained.

Another coverage issue relates to the cost of drugs needed during and after transplantation. “We have had patients on Medicare who, for a multitude of reasons, suddenly can’t afford to take their immunosuppression medications or antibiotics to prevent infection,” Dr. Giralt said. “This is a serious problem. It is really shooting yourself in the foot to cover the whole transplant but not cover life-sustaining medication to prevent graft-versus-host disease (GVHD).”

Many Medicare beneficiaries will incur substantial costs to undergo a bone marrow transplant for one of the approved indications, and they will spend weeks or even months in the hospital after undergoing transplant.5 Patients with standard Medicare Parts A and B coverage with a Medicare Supplement Insurance (or “Medigap”) plan – a policy sold by private companies to help pay some of the health-care costs that standard Medicare plans don’t cover – will incur the least out-of-pocket costs, according to Ms. Farnia. However, those patients with Parts A and B without a Medigap plan must pay deductibles with no out-of-pocket maximum.

Under current Medicare policies, for days one through 60 of any inpatient hospital time within a given calendar year, beneficiaries pay nothing for co-insurance. However, from days 61 to 90, they pay $322 in co-insurance per day and, for each “lifetime reserve day” after day 90 in each benefit period (up to 60 days over their lifetime), they pay $644 in co-insurance per day. For any hospital time beyond the lifetime reserve days, beneficiaries pay all costs.6

Advocating for Change

What is the future for transplant coverage, and how can the transplant community help to enact policy changes? The first step to changing the coverage system is to continue to gather data about the efficacy of transplant, according to Dr. Giralt.

“The transplant community is blessed in that all allo-HCT procedures in North America have to be reported to the registry managed by the CIBMTR,” Dr. Giralt said. “It gives us a data repository, which is essential for any research we want to do.”

For example, there is little likelihood that there would ever be a phase III trial comparing outcomes for patients with myelofibrosis who received transplant with those who received no transplant. However, with data in the CIBMTR registry, a trial could compare transplant outcomes with those of patients in the registry who chose not to undergo transplant, he explained.

From a legislative perspective, Dr. Majhail said that there are a variety of actions that lawmakers and hematologists can take to advocate for improvements in CMS’ coverage of transplant.

“Lawmakers could encourage CMS to come up with a coverage process that is more appropriate for a procedure like transplantation, where there is good evidence telling us that it is effective and safe in the older population,” he said.

In 2015, Dr. Majhail and Ms. Farnia were involved in the publication of a guideline by the American Society for Blood and Marrow Transplantation (ASBMT) that spelled out the appropriate indications for AHCT and alloHCT, including transplantation in older adults.7 Discussing age in the guideline, ASBMT wrote:

“Age by itself should not be a contraindication to transplantation in patients who may benefit from this procedure. Selected older patients with limited comorbidities and good functional status can safely receive HCT with a relatively low and acceptable risk of non-relapse mortality. Instead of chronologic patient age, evaluations such as functional status, HCT-specific comorbidity index score, [European Group for Blood and Marrow Transplantation] risk score, and Pre-Transplantation Assessment of Mortality risk score can assist in determining risks of non-relapse mortality and transplant candidacy for individual patients.”

“We have to encourage CMS to consider coverage of transplantation that reflects how the transplantation community practices,” Dr. Majhail said.

It is also critical that hematologists work with associations like the American Society of Hematology and ASBMT to advocate for these changes so that older patients can be cared for in an appropriate manner.

Dr. Burns acknowledged that the community of transplanters is a small one, especially in comparison with larger groups like physicians who treat patients with breast cancer, so it will require help from the larger community of health-care professionals who care for transplant recipients. “I would ask hematologists who are not transplanters, but who take care of patients prior to and after transplant, to support our efforts for change,” Dr. Burns said. —By Leah Lawrence 


References

  1. Pasquini MC, Zhu X. Current uses and outcomes of hematopoietic stem cell transplantation: CIBMTR Summary Slides, 2015. Accessed October 1, 2016 from http://www.cibmtr.org.
  2. Centers for Medicare & Medicaid Services. Decision Memo for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Myelodysplastic Syndrome (CAG-00415N). Accessed September 22, 2016 from https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=238.
  3. McClune BL, Weisdorf DJ, Pedersen TL, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28:1878-87.
  4. Centers for Medicare & Medicaid Services. Decision Memo for Stem Cell Transplantation (Multiple Myeloma, Myelofibrosis, and Sickle Cell Disease) (CAG-00444R). Accessed September 22, 2016 from https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=280.
  5. National Heart, Lung, and Blood Institute. What to Expect During a Blood and Marrow Stem Cell Transplant. Accessed September 20, 2016 from https://www.nhlbi.nih.gov/health/health-topics/topics/bmsct/during.
  6. Medicare.gov. Your Medicare Coverage: Inpatient hospital care. Accessed September 20, 2016 from https://www.medicare.gov/coverage/hospital-care-inpatient.html.
  7. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21:1863-69.

Building a Strong Case

Researchers in the transplant community hope that building the strongest case possible for the safety and effectiveness of transplantation in older patients with hematologic malignancies will eventually sway CMS’ opinion in favor of increasing coverage for this population. Here are a few of the trials that have evaluated transplant in older patients and found that, when it comes to HCT, age is just a number.

Transplant With Reduced-Intensity Conditioning in Older AML Patients

A prospective, multicenter, phase II study assessed outcomes of reduced-intensity conditioning transplant in 114 patients (median age = 65 years) with AML. Disease-free survival was 42 percent and overall survival (OS) at two years was 48 percent, outcomes that researchers said “were superior when compared with historical patients treated without HCT.” Rates of GVHD and non-relapse mortality were “lower than expected.”

Source

Devine SM, Owzar K, Blum W, et al. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015;33:4167-4175.

A Meta-Analysis of HCT in Older AML Patients

In a meta-analysis of 13 studies examining HCT in patients with AML ≥60 years of age, researchers reported a three-year relapse-free survival rate of 35 percent, leading them to argue “against using age per se as the sole criterion against stem cell transplantation.”

Source

Rashidi A, Ebadi M, Colditz GA, DiPersio JF. Outcomes of allogeneic stem cell transplantation in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2016;22:651-7.

Allogeneic HCT in Older Patients With MDS

In a trial supported by the CIBMTR, investigators are evaluating outcomes after alloHCT for patients with MDS. Researchers presented data from the first 688 patients enrolled in the trial at the 2015 ASH Annual Meeting, reporting that there was no difference in 100-day mortality or OS between patients 55 to 64 years of age and those ≥65 years. “Age alone should not be a determinant for alloHCT eligibility,” the researchers concluded.

Source

Atallah E, Horowitz MM, Logan B, et al. Outcome of patients 65 years and older with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation compared to patients 55-64 years of age. Abstract #78833. Presented at the 2015 American Society of Hematology Annual Meeting, December 6, 2015; Orlando, FL.

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