On February 8, 2013, the US Food and Drug Administration approved pomalidomide (Pomalyst) for the treatment of patients with multiple myeloma who have received at least 2 previous myeloma therapies, including lenalidomide and bortezomib, but whose disease progressed while receiving these therapies or within 60 days of stopping the last therapy.
Multiple myeloma is the second most common hematologic malignancy after the Non-Hodgkin Lymphomas. According to the American Cancer Society, 21,700 people were diagnosed with multiple myeloma in 2012 and 10,700 died from the disease.1 This represents approximately 1% of all cancers and accounts for about 10% of all hematologic malignancies. Multiple myeloma is a multisystem disease that disproportionately affects older individuals. Often the mnemonic CRAB (C = Calcium (elevated), R = Renal failure, A = Anemia, B = Bone lesions) is used to describe the most common clinical features of the disease.2
Historically, myeloma has been a difficult and frustrating disease to treat. Between 1975 and 1979, the probability of a newly diagnosed patient surviving for 2 years was only 53%.3 Over the past decade, however, there have been significant advances in the understanding of the natural history and pathogenesis of multiple myeloma and factors that influence patient outcomes. This insight has resulted in the development of several highly effective biologically targeted agents for the disease, including the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitors bortezomib and carfilzomib. Regimens incorporating these agents are now providing better disease control and prolonged survival without significantly affecting quality of life, with some clinical trials reporting 2-year survival rates as high as 88%.4
However, inevitably the disease progresses and patients relapse or develop refractory disease that becomes unresponsive to current therapies. This has created an ongoing unmet need for drug developers. Just last month, another treatment option became available for patients with relapsed/refractory disease. On February 8, 2013, the US Food and Drug Administration (FDA) approved pomalidomide (Pomalyst) for the treatment of patients with multiple myeloma who have received at least 2 previous myeloma therapies, including lenalidomide and bortezomib, but whose disease progressed while receiving these therapies or within 60 days of stopping the last therapy. Similar to the existing two immunomodulators, pomalidomide is an oral agent that is given on the first 21 days of a 28-day cycle. The FDA approval was based on the results of a multicenter, randomized, open-label clinical trial that included 221 patients with relapsed and/or refractory myeloma who had received lenalidomide and bortezomib but their disease continued to progress. Patients were randomized to pomalidomide alone or to pomalidomide plus low-dose dexamethasone. The overall response rate was 7% in the pomalidomide-alone arm compared with 29% in the combination arm of pomalidomide plus low-dose dexamethasone; the median response time was 7.4 months with the combination. Side effects of this drug are somewhat typical of the immunomodulator class and include fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper respiratory tract infections, back pain, and fever.4
Pomalidomide is available only through the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) program. Prescribers must be certified for this specific REMS program by enrolling and complying with the REMS requirements. In addition, patients must sign a patient-physician agreement form and comply with the REMS requirements, such as pregnancy testing and contraception requirements. REMS-certified pharmacies can only dispense this medication to patients who are authorized to receive pomalidomide and comply with the REMS requirements.4
Health Plan Perspective
The treatment of multiple myeloma and the costs associated with these treatments have been an ongoing visible area for plan managers. Most plans actively manage access to the current therapies for multiple myeloma with one or more of the following: an active prior authorization process, case management, limited distribution channels, and limited quantity dispensing. Many plans and their customers have seen increasing cost of care for these patients and often 1 or more of these agents are in their top 10 specialty drugs by cost, despite the relative small number of patients on therapy.
The recent introduction of pomalidomide offers new hope for many patients who have relapsed/refractory disease, but at a significant cost. With an anticipated price of $10,000/ month of therapy, it is almost a certainty that plans will actively manage access to this drug. In my discussions with plan thought leaders, I have learned that most plans will reserve access to this drug to its FDA-approved indication, which is for those patients who have progressed and who have had previous therapy with an immunomodulator and a proteasome inhibitor.
Health plan managers also recognize that despite all of the gains in treating myeloma, the disease still lacks a cure for most patients. And while pomalidomide does represent a significant advance in therapy, its mechanism of action is similar to other existing agents. Therefore, from a plan perspective, one of the major unmet needs in this disease is new drugs that work differently from the currently approved treatments.
There are several new classes of drugs in development for multiple myeloma that will continue to offer hope to these patients. For health plans, the introduction of these newer agents will increase the complexity of managing this costly therapeutic category.
1. Siegal R, Naishadham D, Jema A. Cancer statistics 2012. CA: A Cancer Journal for Clinicians. 2012;62(1):10—29.
2. International Myeloma Working Group (2003). Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 121(5):749—757.
3. SEER Cancer Statistics Review 1975-2009. http://seer.cancer.gov/csr/1975_2009_pops09/index.html. Accessed March 13, 2013.
4. Pomalyst website. Celgene Corporation. http://www.pomalyst.com/. Accessed March 15, 2013.