Utilizing New Techniques to Manage Multiple Myeloma

Cincinnati—For decades, managed care executives rarely questioned the costs of oncology treatments. They were always included in the formulary.

However, as specialty drugs become more popular and the price of therapies continues to rise, payers are now applying payment reforms and measuring the quality and value of these new options.

At the AMCP meeting, a pair of speakers discussed the shifting environment in a satellite symposium titled Maximizing Value for Patient Outcomes in Multiple Myeloma: Solving the Cost-Benefit Equation.

Ajay K. Nooka, MD, assistant professor in the division of bone marrow transplant at Emory University’s Winship Cancer Institute in Atlanta, Georgia, said there were 20,520 newly diagnosed cases of multiple myeloma in the United States in 2011, accounting for 1% of all new cancer cases. An estimated 10,610 people died of the disease last year, accounting for 2% of all cancer deaths.

African Americans and males are more likely than Caucasians and females to have multiple myeloma, and the median age at diagnosis is 65 years.

Dr. Nooka said survival depends on the patient’s age, disease stage, and treatment regimen. He used the International Staging System and defined stage I as a serum
ß₂-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL, stage III as serum ß₂-microglobulin ≥5.5 mg/L, and stage II as not fitting the criteria for I or III.

According to a 2005 study that Dr. Nooka cited, median survival in stage I is 62 months (69 months for patients <65 years of age and 47 months for patients ≥65 years of age). Median survival in stage II is 44 months (50 months for patients <65 years of age and 37 months for patients ≥65 years of age), and median survival in stage III is 29 months (33 months for patients <65 years of age and 24 months for patients ≥65 years of age).

In stage I, median survival is 111 months for those undergoing high-dose therapy and autologous stem cell transplantation (ASCT) and 55 months for those receiving conventional chemotherapy. In stage II, median survival is 66 months and 40 months, respectively, for those treatment regimens. In stage III, median survival is 45 months and 25 months, respectively.

Recent therapeutic advances have helped prolong survival, according to a 2008 trial that Dr. Nooka discussed. Patients diagnosed with multiple myeloma after 1996 had a significantly longer overall survival than those diagnosed during or before 1996, with the results consistent up to 120 months after diagnosis (P<.001).

Before starting therapy, Dr. Nooka said clinicians should determine if a patient is eligible for a bone marrow transplant. In younger people, the goals of a transplant are high response rates, a rapid response, an improvement in performance status, and no limit in peripheral blood stem cell (PBSC) mobilization.

If patients cannot undergo a transplant, they should begin with therapies, several of which Dr. Nooka mentioned. In a randomized trial, patients were randomized to take 200 mg of oral thalidomide per day plus 40 mg of dexamethasone per day on days 1 through 4, 9 through 12, and 17 through 20 or dexamethasone alone in the same dosage. The combination treatment group had an overall response rate of 63% compared with 41% for the dexamethasone group (P=.0017), although grade 3 or higher adverse events were significantly more likely in the combination group (P<.001).

Another randomized study found thalidomide plus dexamethasone was significantly more effective in overall response rates than a regimen of vincristine, doxorubicin, and dexamethasone before PBSC mobilization (P=.01) and before high-dose therapy (P=.04). Three months after a transplant, significantly more patients taking thalidomide plus dexamethasone had a complete response compared with those in the vincristine, doxorubicin, and dexamethasone group (P<.001).

Dr. Nooka concluded that a combination of new agents improved response rates in the induction setting and patients with multiple myeloma achieved the best results from high-dose therapy and ASCT if they had at least a very good partial response before undergoing the transplant. In addition, trials that included bortezomib in the induction regimens increased response rates, progression-free survival, and overall survival.

After inducing remission, patients typically received maintenance therapies to decrease the tumor burden after the induction and consolidation therapies. The goals included increasing the depth of response, minimizing toxicity, prolonging the duration of response, and prolonging overall survival. Options for maintenance therapies included lenalidomide, bortezomib, and thalidomide.

Dr. Nooka cited a study that found patients taking lenalidomide as maintenance therapy had a significant improvement in overall survival (P=.03) compared with a placebo group, and the lenalidomide reduced the combined risk of progressive disease, death, or secondary primary malignancies by 47%. Further, 10% of patients taking lenalidomide discontinued therapy due to adverse events compared with 3% of patients taking placebo. The risk of secondary primary cancer was higher in the lenalidomide group (P=.008), but the risk of progressive disease (P<.001) and death (P=.002) was higher in the placebo group.

The study demonstrated that following ASCT, patients taking long-term administration of lenalidomide fared well, although Dr. Nooka said progression-free survival may not be an ideal end point because it does not assess the response to salvage therapy and fails to address whether prolonged therapy is more effective than treatment at progression. Since there were concerns regarding the cost of the drug, Dr. Nooka said a cost-effectiveness analysis might be appropriate before beginning lenalidomide maintenance therapy.

After discussing numerous trials, Dr. Nooka concluded that patients with multiple myeloma can have improved outcomes if clinicians prescribe novel regimens aimed at improving complete response rates, undergo risk stratification of patients, assess their vulnerability to treatments, adopt risk-adapted treatment planning, improve supportive care, provide appropriate prophylaxis, monitor adverse events, and focus on bone health to decrease skeletal-related events.

Costs of Multiple Myeloma Drugs and Guideline Application

When assessing new multiple myeloma treatments, plans should evaluate patient outcomes, cost shifting, and compliance, according to Jeffrey Dunn, PharmD, MBA, formulary and contract manager at SelectHealth in Murray, Utah.

Other considerations include the efficacy and tolerability of treatments, drug acquisition costs, administrative burdens, complexity of therapies, direct and indirect costs, and patient education and supportive care. Benefit design factors such as whether the drugs are covered under the medical or pharmacy benefit, whether patients should contribute a copay or coinsurance, and whether to include the drugs on a specialty tier should also be considered, according to Dr. Dunn.

From a provider perspective, Dr. Dunn said it is important to understand fee schedules and reimbursement, the location of therapy, the route of administration and any incentives for oral drugs versus injections, the support for mandated clinical pathways, and issues concerning management of oncology networks.

In oncology, more drugs are being moved from the medical to pharmacy benefit, according to Dr. Dunn, who expects more drugs currently covered under the medical benefit to be reviewed by pharmacy and therapeutics committees. He added that plan sponsors have hesitated in implementing the changes for oncology drugs, however, there has recently been a growing interest because of rising costs, emerging delivery channels, specialty tiers, and biosimilars, which are expected to hit the market in the next few years.

Under the pharmacy benefit, cancer treatments were the third largest specialty category in 2010 with a per member per year (PMPY) spend of $21.81, trailing only inflammatory conditions ($37.16) and multiple sclerosis ($29.80), according to data from the Express Scripts Drug Trend Report. Dr. Dunn said that with several biologic oncology drugs in the pipeline, cancer could soon have the highest PMPY spend among specialties.

When planning benefit designs for oncology drugs, Dr. Dunn said most plans use cost-management methods applied to other chronic diseases such as asthma and hypertension, but there is no standard approach.

Dr. Dunn cited a survey from the Zitter Group, a managed markets consulting firm, where payers said cancer was the highest management priority, ahead of diabetes, asthma, hyperlipidemia, rheumatoid arthritis, and all other disease categories. The survey also found that payers believed they could cut 22.7% of the costs associated with cancer treatment without negatively impacting health outcomes. Oncologists and practice managers replied they could reduce costs by 18.0% and 15.9%, respectively, without affecting outcomes.

In the Zitter Group survey, 46% of payers said they somewhat or strongly agreed with the following statement: “My organization effectively manages the oncology category.” The proportion of those agreeing with the statement was the same as in the summer of 2011, but up from 38% in the winter of 2011 and 25% in the summer of 2010.

The most common tool to manage cancer therapies was prior authorization, followed by tying a drug’s approval to diagnostic tests/biomarkers, having a compendia listing guideline requirements, setting quantity limits, having a specific lab or diagnostic value, and implementing clinical treatment pathways.

Unlike traditional methods such as reducing reimbursement to oncologists and increasing the use of prior authorization, Dr. Dunn said clinical pathways are becoming more popular. He defined clinical pathways as specifying the interventions to perform in a certain sequence. Potential benefits of pathways, according to Dr. Dunn, include decreasing costs, reducing variation, improving outcomes, and evaluating new therapies and clinical approaches.

However, the wider adoption of pathways faces challenges such as complexities of treatment regimens, off-label use of drugs, and a lack of consensus among the guidelines. Dr. Dunn said pharmacists can help by stratifying the guidelines by costs and survivability rates, developing a standard plan with reimbursement aligned with the protocol, encouraging the use of preferred protocols via a tiered oncology program, and reducing the large variations that occur in the late stages of care.

Managed care can play a major role in treating multiple myeloma and setting up a benefit design, according to Dr. Dunn. He said the number of drugs to treat the disease will likely increase in the coming years, following the July 2012 approval of carfilzomib and with numerous products in phase 3 development, including pomalidomide, elotuzumab, panobinostat, perifosine, and plitidepsin.

Dr. Dunn recommended that managed care pharmacists collaborate with other healthcare professionals to encourage patients to adhere to long-term oral therapies for multiple myeloma, evaluate outcomes, implement patient education tools, adopt electronic medical records, and share the treatment plan and goals with oncology doctors, primary care physicians, and specialty pharmacists.