Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials

Abstract

Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatmentrelated side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomibthalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials MP. 11,12 In patients aged 75 years or over, the efficacy of VMP was less evident: the 3-year OS was shorter in comparison with patients aged under 75 years (55% vs. 74%). The incidence of any grade 3-4 AEs was 91% and bortezomib discontinuation rate due to AEs was 34%. Both VMP and MPT are now considered the new standards of care for newly diagnosed MM patients aged 65 years or over. Recently, the combination of bortezomib and thalidomide with or without alkylating agents has shown to be highly effective. 13,14 The weekly administration of bortezomib reduced the incidence of AEs, especially peripheral neuropathy and gastrointestinal toxicity, without affecting efficacy.13,14 Nevertheless, outcome was mainly improved for patients aged under 75 years, while limited advantage was reported in patients aged 75 years or over.14 These data lead to the question as to whether less toxicity may translate into more efficacy, especially in unfit elderly patients.In this meta-analysis of individual patient data from 4 randomized trials, we assessed the influence of age, organ damage, development of treatment-related AEs and drug discontinuation as predictive factors of outcome in elderly newly diagnosed MM patients receiving MP, MPT, VMP, or bortezomib and thalidomide combination (bortezomib, thalidomide and prednisone [VTP] or bortezomib, melphalan, prednisone and thalidomide [VMPT]). Design and Methods Study design and treatmentsPa...

Limiting early mortality: Do's and don'ts in the management of patients with newly diagnosed multiple myeloma

“…Factors previously identified include demographic, nonmodifiable ones (age, gender, and household income) [16][17][18], presence of renal failure [17,18], development of cardiac, infectious and gastrointestinal toxicity of therapy and need to interrupt therapy due to adverse events [17], serum albumin <3.5 g/dL, and serum beta 2 microglobulin >6.5 mg/dL and the absence of novel agents in the treatment regimen [18]. Therefore, we assembled a series of recommendations ("do's and don'ts") regarding the initial management of patients with MM that we believe may help avoid and overcome early complications, some of which can be fatal.…”

Once-Weekly 1.6 mg/m2 Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy

“…It is critical that efficacy must be balanced against risk of toxicity of therapy, and emphasis is given to maintaining good quality of life in unfit older adults with MM [8]. Treatment discontinuation due to therapy-related adverse events is an important factor that negatively impacts outcome [13]. Indeed, interruption translates into dose-reduction and reduced cumulative dose-intensity, affecting efficacy of therapy.…”

Age and aging in blood disorders: multiple myeloma

“…There was no difference in impact of toxicity and discontinuation rate on OS between the treatment regimens. 22 On the other hand, even more intense therapy including bortezomib-based induction therapy, followed by intermediate dose melphalan and autologous stem cell transplantation and lenalidomide maintenance was found to be feasible in fit elderly patients. But again, the death rate related to adverse effects was found to be significantly higher in the patients aged 70 years or over (5 of 26 vs. 3 of 76 patients).…”