Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

Abstract

Multiple myeloma patients deemed to not be candidates for high-dose therapy followed by stem cell rescue who nonetheless need chemotherapy have traditionally received an oral regimen combining melphalan and prednisone. With the advent of novel agents, however, such as immunomodulatory drugs and proteasome inhibitors that are active in the relapsed/refractory setting, there has been an impetus to incorporate these new options into front-line therapy. Several phase II studies have recently revealed that addition of either thalidomide, lenalidomide, or bortezomib to melphalan and prednisone increased the overall and complete response rates, albeit at the cost of some increased toxicity. Randomized phase III studies of melphalan and prednisone with thalidomide have already shown that, compared to melphalan and prednisone alone, the three-drug regimen prolonged time to progression and overall survival in this population, thereby defining a new standard of care. Moreover, our increasing knowledge of the molecular role that cytogenetic abnormalities play in the biology of multiple myeloma and our growing chemotherapeutic armamentarium are beginning to allow us to rationally select therapies based on these characteristics of each patient's disease. Such a risk-and molecular-adapted strategy to the therapy of multiple myeloma promises to revolutionize and personalize our care of these patients and bring us closer to a cure for this disease.Using the diagnostic criteria recommended by the International Working Group, patients with multiple myeloma are classified as having either asymptomatic or symptomatic (Table 1) disease. 1 The latter population, generally considered candidates for a chemotherapy-based intervention, are then further divided into those who either are or are not eligible for high-dose chemotherapy followed by stem cell rescue. 2 Criteria that are weighed to help make this second distinction have generally included age, performance status, and co-morbid medical conditions. 2 There is some variability in these parameters and how they are applied, since studies examining stem cell transplantation have used different criteria. In regard to age, for example, which is the most objective of these measures, initial studies tended to enroll patients younger than 65 years of age, 3 while more recent studies suggest that transplant is safe in at least some who are over the age of 70 (for example 4,5 ). On the other hand, data suggesting that patients with poor-risk chromosomal features have a short time to progression after autologous transplantation have led to suggestions that even younger patients with these abnormalities may not be candidates for standard approaches. Nonetheless, as little as two years ago, there was general agreement that the standard of care for patients who were not eligible for transplantation and yet needed chemotherapy was melphalan

Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

“…In our retrospective study, there were no between‐group differences in the parameters studied ( P = 0.880). These results are in contrast to several randomized prospective studies and a retrospective study in the literature . The discord may be due to differences between the present study and the studies in the literature.…”

“…The low power due to the small numbers may contribute to the difference between previous studies and our study, but it may not be the main reason. The prevalence of side effects with the therapies was in accordance with that reported in the literature .…”

“…The quality of the response to the novel drug protocol was statistically significantly better than the response to the conventional therapy. Some reviews reported that treatment with the new drug protocols in non‐transplant candidate patients with MM improved the quality of the treatment response and prolonged their OS. In our retrospective study, there were no between‐group differences in the parameters studied ( P = 0.880).…”

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

“…Patients ineligible for SCT due to their age, performance status, comorbidities, or other factors have in the past received melphalan plus prednisone as the standard of care for induction therapy 38. However, other combinations have emerged, with the evidence base, in particular, supporting the combination of melphalan, prednisone, and thalidomide27,39 and most recently melphalan, prednisone, and bortezomib 40.…”

Tratamento de primeira linha no Mieloma Múltiplo

“…Além disso, o MPT induziu maior SLE e SG do que a abordagem com Mel 100 (p =0,001 e p = 0,004, respectivamente). Baseado nesses resultados, Orlowski 16 acredita o MPT possa ser considerado como o padrão-ouro para tratamento inicial de pacientes idosos e sintomáticos com MM. Lenalidomida (Revlimid), um novo agente imunomodulatório mais potente e menos tóxico do que a talidomida, poderá ser uma futura opção a essa última no MPT.…”