Improved survival in multiple myeloma and the impact of novel therapies

Abstract

Treatments for myeloma have expanded in the last decade, but it is not clear if the introduction of novel therapies and the increased use of high-dose therapy have translated into better outcome for patients with myeloma. We examined the outcome of 2 groups of patients seen at a single institution, one from time of diagnosis and the other from the time of relapse, to examine the survival trends over time. Among 387 patients relapsing after stemcell transplantation, a clear improvement in overall survival from the time of relapse was seen, with those relapsing after 2000 having a median overall survival of 23.9 versus 11.8 months (P < .001) for those who relapsed prior to this date. This improvement was independent of other prognostic factors. Patients treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse (30.9 vs 14.8 months; P < .001). In a larger group of 2981 patients with newly diagnosed myeloma, those diagnosed in the last decade had a 50% improvement in overall survival (44.8 vs 29.9 months; P < .001). In this study, we demonstrate improved outcome of patients with myeloma in recent years, both in the relapsed setting as well as at diagnosis. IntroductionMultiple myeloma (MM), a neoplasm of plasma cells, affects 1 to 5 per 100 000 individuals each year worldwide with a higher incidence in the West. 1 It is the second most common hematologic malignancy in the United States, and it is estimated that there will be 19 900 new diagnoses and 10 790 deaths due to myeloma in 2007. 2 The median survival of patients with MM was less than a year before introduction of alkylating agents, and the introduction of melphalan in the 1960s resulted in improved survival. 3,4 A timeline of major therapeutic advances in multiple myeloma is outlined in Table 1. In the 1980s, introduction of high-dose chemotherapy and stem-cell rescue (ASCT) was introduced, and randomized trials since have demonstrated a survival advantage for this modality compared with conventional chemotherapy (CCT). [5][6][7] The introduction of thalidomide represented a major milestone in the treatment of myeloma, and the subsequent availability of its analog lenalidomide and the proteasome inhibitor bortezomib have expanded the therapeutic armamentarium for myeloma. [8][9][10][11][12] Incorporation of these novel agents has resulted in a paradigm shift in the treatment of myeloma, with their use earlier in the disease course. 13 While the new drugs have allowed successful salvage of relapsed disease, it is not clear if the survival of patients has improved during the last few years. We examined patients seen at our institution over a 36-year period to determine whether there has been an improvement in survival of myeloma patients seen during this time period. MethodsWe examined 2 cohorts of patients seen at Mayo Clinic with a diagnosis of MM. The first cohort consisted of 387 patients who were examined for potential improvement in survival following first relapse after ASCT. These patients we...

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

“…OS in myeloma has improved significantly in the last decade [34] with the emergence of thalidomide [35], bortezomib [36], and lenalidomide [37,38]. Bortezomib is a proteasome inhbitor [39][40][41]; the mechanism of action of thalidomide and lenalidomide is unclear, but they are considered immunomodulatory agents [42] and may require cereblon (the putative primary teratogenic target for thalidomide) [43] expression for their anti-myeloma activity [44].…”

A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma

“…1 Data from the SEER registry showed a 82 significant trend toward a better 5-year survival for patients diagnosed between [2003][2004][2005][2006][2007]83 whereas no survival improvement was seen in older patients (≥65 years). 2 …”

Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy

“…1 Although the use of novel agents and high-dose therapy has improved overall survival (OS), 2 MM remains incurable; nearly all patients relapse or become refractory to treatment. Thus, more treatment combinations are needed, especially for those patients who have exhausted all available treatment options.…”