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Long-term outcomes key to cost-effectiveness of tisagenlecleucel for pediatric leukemia

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October 3, 2018

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John K. Lin

Although tisagenlecleucel is a clinically important therapy in pediatric relapsed or refractory B-cell acute lymphoblastic leukemia, additional research is needed to determine long-term outcomes, according to a study published in Journal of Clinical Oncology.

“Tisagenlecleucel provides impressive short-term remissions for children with relapsed ALL — its long-term performance is the main question,” John K. Lin, MD, fellow in VA Health Services Research and Development at Center for Health Policy and Center for Primary Care and Outcomes Research at Stanford University, told HemOnc Today. “At its current price, it provides good value if remissions are durable. If patients relapse, its price would need to be lowered substantially to be cost-effective.”

ALL is the most common malignancy diagnosed among children. Although 5-year survival rates are more than 90%, the prognosis for relapsed or refractory disease is poor and those who survive relapse often require hematopoietic stem cell transplantation.

Chimeric antigen receptor (CAR) T-cell therapy could potentially cure disease in this population without the need for HSCT. However, the cost of a one-time infusion of tisagenlecleucel (Kymriah, Novartis) — the first FDA-approved CAR T-cell therapy that is composed of a CD19 antigen-binding domain, a 4-1BB costimulatory domain, and a CD3-zeta signaling domain — is $475,000, according to the study, making it the most expensive cancer therapy to date.

Lin and colleagues assessed whether the cost of tisagenlecleucel represents reasonable value. The researchers used Markov modeling to evaluate the therapy in pediatric relapsed or refractory ALL from a U.S. health-payer perspective during a lifetime horizon.

Life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio, at a 3% discount rate, served as primary outcomes.

When the researchers assumed a 40% 5-year RFS rate, tisagenlecleucel conferred an increased life expectancy of 12.1 years at a cost of $61,000 per QALY gained.

Conversely, when assuming a 20% 5-year RFS rate, life expectancy increased by 3.8 years for $151,000 per QALY gained. This was followed by an increased life expectancy of 5.7 years for $184,000 per QALY gained when assuming a 0% 5-year RFS rate.

Tisagenlecleucel was the most expensive treatment strategy — when considering total costs of treatment, including preinfusion chemotherapy, administration and complications — at $548,000 to $599,000, compared with $282,000 to $374,000 for blinatumomab (Blincyto, Amgen), clofarabine combination therapy, and clofarabine monotherapy.

At a 5-year RFS rate of 20%, reducing the price of a one-time infusion of tisagenlecleucel from $475,000 to $200,000 would confer a $100,000 per QALY willingness-to-pay threshold, and reducing it to $350,000 would confer a $150,000 per QALY willingness-to-pay threshold.

“Another alternative for improving the value of CAR T-cell therapy is extending a money-back guarantee to refunding the price of therapy if a patient relapses within 1 year,” Lin said. “Currently, if the patient does not achieve initial remission within the first month, they are not responsible for payment.” – by Jennifer Southall

For more information:

John K. Lin, MD, can be reached at The Center for Primary Care and Outcomes Research at Stanford University, 117 Encina Commons, Stanford, CA 94305; email: johnklin@stanford.edu.

Disclosures: Lin reports no relevant financial disclosures. One author reports a consultant/advisory role with and research funding and travel expenses from Novartis.