José M. Hernández

Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells

The present study explored the impact of two novel criteria; having >95% abnormal plasma cells by flow cytometry at diagnosis and the evolving subtype of the disease, as predictors of progression in 61 smouldering multiple myeloma (SMM) and 311 monoclonal gammopathy of unknown significance (MGUS) patients. Although both criteria were of prognostic value, the risk of progression was better identified by immunophenotyping [Hazard Ratio (HR) 6·2 and 17·2 for SMM and MGUS, respectively] than evolving subtype, which had independent prognostic value only in MGUS (HR 3·6). Immunophenotyping discriminated the different risk of progression within the evolving and non‐evolving subgroups of SMM (P = 0·01) and MGUS (P < 0·001).

Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression

Novel therapeutic agents have become available for patients with multiple myeloma in the last few years. This study conducted by the Spanish PETHEMA and GEM groups investigated the effect of bortezomib plus melphalan and prednisone in elderly patients with newly diagnosed multiple myeloma. Treatment was highly active and well tolerated, with 85% of patients alive at 3 years. Background New treatment options offering enhanced activity in elderly, newly diagnosed patients with multiple myeloma are required. One strategy is to combine melphalan and prednisone with novel agents. We previously reported an 89% response rate, including 32% complete responses and 11% near complete responses, in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP) in 60 newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we report updated time-to-events data and the impact of poor prognosis factors on outcome. Design and Methods Updated analyses of time to biochemical progression and overall survival with VMP were conducted, and compared with those of historical controls treated with melphalan and prednisone. A univariate analysis was performed to evaluate the influence of known prognostic factors on the time to progression. Results After a median follow-up of 26 months, the median time to progression with VMP was 27.2 months, compared with 20.0 months with melphalan plus prednisone. The median overall survival with VMP was not reached versus 26 months with melphalan and prednisone; the survival rate at 38 months was 85% versus 38%, respectively. Time to progression was not significantly affected by elevated β2-microglobulin or lactate dehydrogenase levels, advanced age, or cytogenetic abnormalities, but was shorter in patients with albumin <3 g/dL, Karnofsky performance status ≤70%, bone marrow plasma cell infiltration ≥40%, and, particularly, high plasma cell proliferative activity (≥2.5% S-phase cells). Conclusions VMP is highly active and well tolerated in elderly patients with newly diagnosed muktiple myeloma, with 85% of patients alive at 3 years. Moreover, VMP may overcome the poor prognostic impact of various factors, particularly cytogenetic abnormalities.