Medical World News: Clinical Updates

Tisagenlecleucel's High Price Aligns With Its Benefit in Pediatric B-ALL, Study Results Find

Despite the high cost of tisagenlecleucel (Kymriah), the chimeric antigen receptor (CAR) T-cell therapy to treat pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), the benefits of the treatment support the price, according to research in JAMA Pediatrics.

A group of researchers that included individuals from the Institute for Clinical and Economic Review compared life-years gained, quality-adjusted life-years (QALYs) gained, and incremental costs per life-year and QALY gained of tisagenlecleucel with the chemoimmunotherapeutic agent clofarabine (Clolar).

Although research has shown that tisagenlecleucel has higher rates of re- sponse, event-free survival, and overall survival compared with other therapies used to treat this population, the “follow-up for patients receiving tisagenlecleucel is limited, with a maximum duration of less than 4 years; therefore, uncertainty remains around its long-term benefit,” the authors explained.

They used a decision analytic model to extrapolate trial evidence from 3 studies and collected all costs and outcomes expected from the CAR T-cell therapy. They analyzed the therapy from a payer perspective and estimated outcomes over a patient’s life.

They found that more than 40% of patients who initiated tisagenlecleucel would become long-term survivors or would be alive and responding to treat- ment after 5 years. In comparison, only 10% of patients who receive clofarabine would be long-term survivors.

The total discounted cost of tisagenlecleucel was $667,000, with 10.34 discounted life-years gained and 9.28 QALYs gained. Clofarabine had a total discounted cost of $337,000, with 2.43 discounted life-years gained and 2.10 QALYs gained. The approximate incremental cost-effectiveness ratio of tisagenlecleucel versus clofarabine was $42,000 per life-year gained and $46,000 per QALY gained.

The researchers ran multiple scenarios to account for long-term relapse and survival, and the cost-effectiveness estimates ranged from $37,000 to $77,500 per QALY gained. They concluded that tisagenlecleucel is priced in alignment with its benefits over a patient’s life.

“Financing cures in the United States is challenging owing to the high up-front price, rapid uptake, and uncertainty in long-term outcomes; however, innovative payment models are an opportunity to address some of these challenges and to promote patient access to novel and promising therapies,” the authors wrote.


Whittington MD, McQueen RB, Ollendorf DA, et al. Long-term survival and value of chimeric antigen receptor T-cell therapy for pediatric patients with relapsed or refractory leukemia [published online October 8, 2018]. JAMA Pediatr. doi: 10.1001/jamapediatrics.2018.2530.

Three Genetic Types Drive Higher Prevalence of Multiple Myeloma in African Americans

Multiple myeloma (MM) occurs 2 to 3 times more frequently in Americans of African descent than in Americans of European descent, and a new study1 has identified 3 gene types that account for this disparity.

The paper, published in Blood Cancer Journal, demonstrated that the disparity is largely driven by disparities in the occurrence of the t(11;14), t(14;16), and t(14;20) subtypes of MM.1

“We sought to identify the mechanisms of this health disparity to help us better understand why myeloma occurs in the first place and provide insight into the best forms of therapy,” Vincent Rajkumar, MD, a hematologist at Mayo Clinic and senior author of the study, said in a statement.2

The researchers studied 881 patients with monoclonal gammopathies. Whereas previous research into disparities in prevalence of disease has relied on self-reported race, this study identified the ancestry of patients through DNA sequencing. Self-reported race can result in bias, but the DNA sequencing allowed researchers to determine ancestry more accurately, Rajkumar said.

In the entire cohort, the median African ancestry was 2.3%, the median European ancestry was 64.7%, and the median Northern European ancestry was 26.6%. To better observe differences in the prevalence of MM subtypes, the authors separated the cohort into the most extreme populations with regard to African ancestry.

“Although many individuals in the US are of mixed ancestry, ancestral characterization of patient cohorts is required to fully understand how the role of human genetic variation associated with ancestry impacts health disparities,” the authors wrote.

They found that the probability of having 1 of the 3 subtypes associated with higher risk of MM was significantly greater in the 120 individuals who had at least 80% African ancestry compared with the 235 individuals who had less than 0.1% African ancestry.

Previous research3 has shown that despite being more likely to be given a diagnosis of MM, African Americans are underrepresented in MM disease research. As a result, improved overall survival for MM has largely been observed in Caucasian patients.

“There are efforts to enroll more minorities in clinical studies, and this is important,” Rajkumar said. “However, it is equally, if not more important, to determine the mechanisms of racial disparities in terms of why cancers occur more often in certain racial groups. Our findings provide important information that will help us determine the mechanism by which myeloma is more common in African Americans, as well as help us in our quest to find out what causes myeloma in the first place.”


1. Baugh LB, Pearce K, Larson D, et al. Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. Blood Cancer J. 2018;8(10):96. doi: 10.1038/s41408-018-0132-1.
2. Dangor J. Mayo Clinic researchers identify gene types driving racial disparities in myeloma [press release]. Rochester, MN: Mayo Clinic; Accessed October 15, 2018.
3. Manoklovic A, Christofferson A, Liang WS, et al. Comprehensive molecular profiling of 718 multiple myelomas reveals significant differences in mutation frequencies between African and European descent cases. PLoS Genet. 2017;13(11):e1007087. doi: 10.1371/journal.pgen.1007087.
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