Transplant Age
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 .
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 .
“ This is a serious problem . It is really shooting yourself in the foot to cover the whole transplant but not cover lifesustaining medication to prevent graftversus-host disease .”
— SERGIO A . GIRALT , MD
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 authoriza-
58 ASH Clinical News November 2016