The overall incidence of hematologic cancers is lower than that of solid tumor malignancies, such as lung, breast, and colorectal cancers, for payers who are responsible for keeping track of and for managing the entire portfolio of oncology. Hematologic cancers bring unique challenges from a treatment perspective and a supportive care perspective.
These considerations translate to unique consideration requirements, challenges, and opportunities for payers. The 2012 ASH meeting brought with it much anticipated data supporting novel therapies. Several retrospective analyses were also shared that evaluated existing treatments, best-practice medical interventions (eg, hematopoietic-cell transplantation), the value of medications, and other interventions as seen through calculations of cost-effectiveness.
Promising Emerging Medications
One example of a novel medication with exciting phase 2 results is quizartinib. Quizartinib is being studied for the treatment of patients with high-risk, refractory acute myeloid leukemia (AML). The data presented show a 46% complete response rate after 28-day cycles of quizartinib monotherapy in a population that failed salvage chemotherapy or that had relapsed after stem-cell transplant. What makes this even more impressive is that the majority of patients were at very high risk as a result of their genetic profiles, including the FLT3-ITD mutation. In a population that previously did not have an opportunity to bridge to a potential curative allogeneic stem-cell transplant, 34% of the patients were successfully bridged to transplantation.
Further development of quizartinib’s clinical profile will be important to monitor to define its place in therapy. This includes defining the appropriate patient, including a genetic profile, as well as when quizartinib is used within the continuum of therapy. These factors will influence the management and the potential value as defined by payers.
Ross L. Levine, MD, presented data on newly discovered genes that have prognostic significance in treating patients with AML. Having the ability to classify patients into various risk profiles may help guide therapy. For example, a recent post hoc analysis found that high-dose daunorubicin had a greater 3-year overall survival compared with standard-dose daunorubicin in patients with high-risk mutations or translocations. These data may also help shape guideline development and corresponding coverage criteria. Payers will evaluate the sensitivity, specificity, and the cost of these genetic tests and consider the relative prognostic value in a real-world setting.
Shaji K. Kumar, MD, presented data on an investigational oral proteasome inhibitor, MLN9708. This could be the first oral proteasome inhibitor for the treatment of multiple myeloma (MM). During a 12-month time frame, the overall response rate was more than 90%; however, MLN9708 was studied in combination with lenalidomide. Payers are familiar with the use of combination therapy for the treatment of patients with MM.
However, if these data are confirmed in later phase studies, the US Food and Drug Administration (FDA) could approve combination therapy with novel agents for the treatment of MM, which is primarily recommended by the National Comprehensive Cancer Network (NCCN), but without formal FDA approval. Determining the value of all of the various combinations of currently available therapy, as well as the most appropriate line of therapy, is very difficult in patients with MM.
Mitchell S. Cairo, MD, presented interesting data demonstrating a cost reduction for inpatient stays, shorter lengths of stay, and lower corresponding charges when rasburicase was used in lieu of allopurinol for the treatment of acute tumor lysis syndrome. Regarding this relatively rare condition, records from more than 400 hospitals were evaluated to profile 130 patients, of which approximately 25% received rasburicase. The average lengths of stay were 5 days less for the group that received rasburicase. Hospitals with specific-use criteria for rasburicase should evaluate these data to validate their criteria.
The outstanding question is the potential for the cost-effective use of rasburicase in the outpatient setting. Without these data, payers should continue to monitor the need to manage the use of rasburicase in the outpatient setting while keeping in mind the acquisition cost of these products as well as the available clinical data.
Recently Approved Therapies
Several recent advances have been reported in hard-to-treat leukemia. The FDA approved bosutinib in September 2012 and omacetaxine mepesuccinate in October 2012 to treat various phases of chronic myeloid leukemia (CML). Vincristine sulfate liposome injection was approved in August 2012 to treat Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL).
In December 2012, the FDA approved ponatinib 3 months ahead of schedule for the treatment of CML and Philadelphia chromosome–positive ALL.
Jorge E. Cortes, MD, presented data on the use of ponatinib in patients who otherwise had no therapeutic alternatives. Ponatinib is a tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in patients who have failed other TKI therapies, including first- and second-line TKI therapies. In particular, if a patient has a T315I BCR-ABL mutation, the other existing TKIs, including bosutinib, dasatinib, nilotinib, and imatinib, are considerably less effective.
According to Dr Cortes, patients with mutations other than T315I respond very well, with a total of 57% having a major cytogenetic response. Dr Cortes also noted that ponatinib is very well tolerated, but it does, however, carry a Boxed Warning about blood clots and liver toxicity.
Opportunities for Payer Management
These therapies for CML and ALL also provide opportunities for keen payer management. Particularly in patients with chronic-phase CML, oral TKI therapy may be used for years to maintain cytogenetic response. Robert C. Hermann, MD, FACP, presented data regarding the use of cytogenetic assessments from a registry of patients with newly diagnosed CML. The majority of patients (96%) in the analysis had chronic-phase CML, and 73% of patients were started with imatinib as first-line therapy.
Disease burden while patients were receiving imatinib was most frequently assessed by blood counts, with only 16% having had a molecular assessment at 3 months, 47% at 12 months, and 64% at 36 months. Cytogenetic testing was even less common. According to Dr Hermann, only approximately 25% of the patients receiving imatinib had a complete cytogenetic response by 12 months and by 18 months, and approximately 25% achieved a major molecular response, which is lower than reported in clinical trials.
What is not known from these data is if cytogenetic testing was completed more in populations of higher risk based on genetic profiles or on physical condition, or if molecular testing was more readily available in certain clinics that possibly have more specialized hematologists. This may have led to an adverse selection of patients being tested compared with those who were not tested. Either way, the NCCN now recommends the early assessment of molecular response.
With the expanding treatment options for patients with CML, some payers are looking to TKI therapy as an opportunity to manage products. Imatinib is currently the least expensive TKI for CML on a monthly basis, and it is expected to become available as a generic in 2015. Dasatinib and nilotinib have similar FDA-approved indications, and they are considered by many payers to have similar efficacy. This is an area in oncology where payers may start to prefer an agent or agents through step therapy or prior authorization.
Another initiative taken by several specialty pharmacies and some payers is an effort to increase adherence. The importance of adherence is demonstrated by Dr Hermann’s presentation of improved 3-year survival in patients who received imatinib more than 85% of the days compared with those who were less adherent to therapy. These therapies are expensive, and poor adherence contributing to inadequate cytogenetic response may make the spending wasteful. It behooves payers to make efforts to tackle patient nonadherence.
Meeting the Challenge
Overall the ASH annual conference presented a large variety of data for upcoming new therapeutic entrants, as well as for existing treatment options. With these data, new challenges and opportunities emerge for payers who are charged with the responsibility of trying to manage this exciting realm in hematologic cancers.