Introduction: Essentials for Tailoring Multiple Myeloma Therapy

Hematologists/oncologists and other physicians can expect to encounter an increasing number of patients with multiple myeloma in the coming years. Between 1997 and 2006, the incidence rate of myeloma declined in the United States, but the burden (the number of incident cases) increased.[1] An analysis of population-based cancer registries in nine countries detected modest increases in the incidence of multiple myeloma in most registries between 1973 and 1992, with further increases projected by 2007.[2]

Historically, multiple myeloma has been a difficult and frustrating disease for patients and physicians. Since the reintroduction of thalidomide (Thalomid) and the development of lenalidomide (Revlimid) and bortezomib (Velcade), outcomes have improved considerably, particularly when these newer agents are combined with conventional chemotherapeutic agents or with each other. Using the first-line regimens common in 1983, typical 2-year survival rates were 48% to 66%. In trials of triple combination therapy reported in 2008, the 2-year survival rates ranged from 83% to 90%.[3] In the United States, the 5-year survival rate improved from 26% in 1975 through 1977 to 34% in 1996 through 2003, a statistically significant difference.[4]

Obviously, it is vitally important for today’s physicians to understand the newer agents, but this is a challenge because the drugs have multiple functions (eg, antiangiogenesis, immunomodulation, proteasome inhibition), have different toxicity profiles, and can be used in myriad combinations and sequences. Hematologists/oncologists have indicated a need to know more about choosing first-, second-, and third-line therapies; the side effects of the new agents; the role and timing of stem cell transplantation in the era of the new therapies; guidelines for maintenance therapy; and what new therapeutic combinations will be a major factor in treating myeloma in the coming years.[5-7]

This supplement to ONCOLOGY was planned by myeloma experts at a roundtable held April 24, 2009, in Philadelphia. Among other discussions, we compared efficacy and safety data for the various therapies recommended for newly diagnosed myeloma patients and those with relapsed/refractory disease. For patients eligible for autologous stem cell transplantation (ASCT), older regimens such as vincristine/doxorubicin/dexamethasone, liposomal doxorubicin/vincristine/dexamethasone, and single-agent dexamethasone are no longer preferred because rates of complete response, as well as overall response rates and regimen-related morbidity and mortality, favor newer drug combinations. The four newer regimens whose use is based on level 1 evidence and consensus are bortezomib/dexamethasone, bortezomib/doxorubicin/dexamethasone, bortezomib/thalidomide/dexamethasone, and len­alidomide/low-dose dexamethasone. Dr. Edward Stadtmauer provides guidance for choosing among these regimens, with particular attention to patients who have cytogenetic abnormalities, renal disease, or other negative prognostic indicators.

Dr. Ruben Niesvizky, Dr. Tomer Mark, and Dr. Morton Coleman discuss front-line treatment of myeloma patients who cannot or choose not to undergo ASCT. For this group, the initial treatment regimens most highly recommended are melphalan (Alkeran)/prednisone/thalidomide, bortezomib/melphalan/prednisone, and lenalidomide/low-dose dexamethasone. Melphalan/prednisone may be appropriate for a small number of patients with serious comorbidity and/or poor performance status. Dr. Niesvizky reviews the circumstances that may make one or another of the newly established standards preferable for certain patients. Data from phase II trials suggest high efficacy rates for melphalan/prednisone/lenalidomide, clarithromycin/lenalidomide/dexamethasone, and lenalidomide/bortezomib/dexamethasone, among other emerging regimens.

Dr. Richardson and colleagues close the series by reviewing the treatment of relapsed/refractory disease. For these patients, the newer regimens that are based on level 1 evidence and consensus are single-agent bortezomib, bortezomib/liposomal doxorubicin, and lenalidomide/dexamethasone. To assist clinicians in choosing among these and other regimens, Dr. Richardson addresses the influence of prior therapy, optimal treatment sequencing, drug resistance, side-effect management, and considerations in treating patients with renal disease, extramedullary disease, and extensive bone disease.

It is hoped that the information in these supplements will help community oncologists understand the latest standards for myeloma care and feel more confident about participating in this exciting, fast-changing field.

-Sundar Jagannath, MD

Address all correspondence to:Sundar Jagannath, MD
St. Vincent’s Comprehensive Cancer Center
325 West 15th St
New York, NY 10011
e-mail: sjagannath@aptiumoncology.com