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The association of diabetes and anti-diabetic medications with clinical outcomes in multiple myeloma.

ABSTRACT:

Background

Insulin/insulin-like growth factor-1 signalling may underlie the promoting effect of type 2 diabetes on cancer. This study examined the association of diabetes, including steroid-induced diabetes (SID), and the impact of anti-diabetic medication on clinical outcomes of multiple myeloma (MM).

Methods

A retrospective review was conducted of 1240 MM patients. Overall survival (OS) and MM disease status prior to death were analysed.

Results

Diabetic patients had a significantly shorter OS than non-diabetic patients (median: 65.4 vs 98.7 months). In multivariate analysis, SID was a significant predictor of decreased OS, along with age, comorbidity, MM stage, and cytogenetic abnormalities. Analyzing only the diabetic MM patients, Cox regression showed that metformin predicted an increased OS, whereas use of insulin/analogues predicted a decreased OS. Competing risk analysis showed that DM was associated with increased cumulative incidence of death with progressive MM. Among the diabetics, multivariate regression showed that insulin/analogues were associated with increased, but metformin with decreased death with progressive MM. Potential immortal time bias was evaluated by landmark analyses.

Conclusions

DM, SID in particular, is associated with poor clinical outcomes in MM. Insulin/analogues are associated with poor outcomes, whereas metformin is associated with improved outcomes. No conclusion about causal relationships can be made at this time. Managing hyperglycaemia with non-insulin regimens should be investigated in randomised trials.

SUBMITTER: Wu W

PROVIDER: S-EPMC4119980 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide greater options to individualize treatment and help patients achieve a clinically meaningful response.