Researchers Say Breakthrough Blood Cancer Therapies Are Worth the High Cost, Other Experts Disagree

Are the high costs of breakthrough therapies for blood cancers, some with price tags of more than $100,000 per year, worth the improved outcomes for patients?

A team of researchers at Tufts Medical Center (Tufts MC) in Boston examined this question, conducting a systematic review of peer-reviewed cost-effectiveness analyses. They determined that breakthrough therapies for blood cancers may, in many cases, provide reasonable value for money spent.

“Given the increased discussion about the high cost of these treatments, we were somewhat surprised to discover that their cost-effectiveness ratios were lower than expected,” said senior study author Peter S. Neumann, ScD, director of the Center for Evaluation of Value and Risk in Health at Tufts MC. “Our analysis had a small sample size and included both industry- and non-industry-funded studies. In addition, cost-effectiveness ratios may have changed over time as associated costs or benefits have changed. However, the study underscores that debates in health care should consider the value of breakthrough drugs and not just costs.”

The research team, based at the Tufts MC center, sought out published studies from between 1996 and 2012 in the medical and economic literature and examined the cost utility of innovative treatment agents for blood cancers. In these types of analyses, the cost utility of a drug is defined as a ratio of a drug’s total cost per patient quality-adjusted life year (QALY) gained. This unit of measurement incorporates a treatment’s impact on patients’ length of and quality of life. A lower cost/QALY ratio means a more favorable result as it represents a more efficient way to achieve health gains.

Using the Tufts MC Cost-Effectiveness Analysis Registry the team found 29 studies and grouped them by nine treatment agents (interferon, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide) and four blood cancer types—chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), and multiple myeloma (MM).

The team evaluated factors such as the quality of each study’s methodology and its value to decision makers and compared the cost/QALY ratios reported. After comparing the cost-effectiveness ratios of drugs by disease indication and treatment type, the research team observed that most ratios were lower or more favorable than thresholds commonly used in the United States as benchmarks for cost-effectiveness ($50,000/QALY or $100,000/QALY). The median ratios reported by industry-funded studies ($26,000/QALY) were more favorable than the median reported by non-industry-funded studies ($33,000/QALY). The median reported cost-effectiveness ratio was highest for CML ($55,000/QALY) and lowest for NHL ($21,500/QALY). The analysis was published online in Blood, the Journal of the American Society of Hematology (ASH).

Not everyone in the field agrees that the high costs are justified.

A recent editorial published online in the Blood Journal by a group of 100 CML experts, draws attention to the high prices of approved tyrosine kinase inhibitors for the treatment of CML.

“We believe the unsustainable drug prices in CML and cancer may be causing harm to patients. Advocating for lower drug prices is a necessity to save the lives of patients who cannot afford them,” the authors state. “Pricing of cancer and other drugs involves complex societal and political issues which (1) demand immediate attention and (2) will need to consider many factors and involve many constituencies.…We propose to begin the dialogue by organizing regular meetings, involving all parties concerned, to address the reasons behind high cancer drug prices and offer solutions to reduce them. For CML, and for other cancers, we believe drug prices should reflect objective measures of benefit, but also should not exceed values that harm our patients and society.”

Dr. Hagop Kantarjian, chairman of MD Anderson Cancer Center's leukemia department, has been a vocal advocate for lower drug costs, speaking on the issue at meetings and authoring several articles on the topic since April 2013, according to a recent article in the Houston Chronicle.

He is about to launch a social media campaign to collect the stories and signatures of 1 million cancer patients and survivors affected by drug prices. He plans to use these signatures to lobby Congress to allow the government to negotiate prices with pharmaceutical companies.

“I've come to the conclusion that the only way to make a dent in this issue is to get patients involved," said Kantarjian, according to the Chronicle. “The only way to force elected officials to represent patients is for those patients to go online and let it be known just how harmful those high prices are."

Many of the most expensive drugs recently approved by the FDA are for patients with blood cancers. According to the Chronicle article, these include bosutinib (Bosulif), approved in 2013 for CML which costs $142,000 annually, ibrutinib (Imbruvica), approved in 2013 for MCL and in 2014 for CLL, which costs $168,00 annually, and idelalisib approved in 2014 for CLL, which costs $114,00 annually.

Despite these high costs, these and similar drugs have revolutionized care for those with blood cancers, allowing many patients to manage once-fatal diseases as chronic conditions by taking a pill each day. ASCO recently recognized the approval of four new therapeutic options, obinutuzumab, ibrutinib, ofatumumab, and idelalisib, as the Cancer Advance of the Year, due to their value for patients with CLL. All of these were approved in 2013 or 2014 and may not be represented in the Tufts MC data.

The first of these four agents, approved in November 2013 in combination with chlorambucil as a first-line treatment regimen for patients with CLL, was the anti-CD20 agent obinutuzumab. The approval was based on data from a phase III CLL11 trial. In the study, the obinutuzumab/chlorambucil combination significantly reduced the risk of progression by 84%, when compared with chlorambucil alone.

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib was approved in February 2014 for patients with CLL who have received at least one previous therapy. The decision was based on data from 48 patients enrolled in the single-arm phase Ib/II PCYC-1102-CA study. At a median 15.6-month follow-up for this group, single-agent ibrutinib produced an overall response rate (ORR) of 58.3% (all partial responses) with a duration of response of up to 24.2 months.

The anti-CD20 agent ofatumumab, received a new indication in April 2014, for ofatumumab plus chlorambucil for previously untreated patients with CLL who are considered inappropriate for treatment with the chemotherapy fludarabine. The new approval was based on results from the phase III COMPLEMENT 1 trial, in which ofatumumab and chlorambucil demonstrated a 9.3-month improvement in PFS compared with chlorambucil alone. The ORR with the combination was 82% versus 69% with chlorambucil alone.

In July 2014, the PI3K-delta inhibitor idelalisib was approved in combination with rituximab for patients with high-risk relapsed or refractory CLL. The approval was based on the phase III Study 116 trial, in which the addition of idelalisib to rituximab improved overall survival by 72% and PFS by 82% versus placebo and rituximab.