In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (Revised-Myeloma Comorbidity Index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities.
We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, yet received induction protocols based on physicians’ judgement. DR, serious adverse events (SAEs), response, progression free- (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (<60, ≥70 years [y]) and therapy intensity subgroups at baseline and follow-up.
Fit and <60y patients were mostly treated with full intensity, whereas frail and ≥70y patients usually received DR. Hematological and non-hematological SAEs were more frequently seen in frail vs. ≥70y patients. Dose adaptations were mainly necessary in frail patients. OS and PFS were similar in fit and intermediate-fit but significantly worse in frail patients (p=0.0245/ p<0.0001), whereas in age-based subgroups, OS- and PFS-differences did not reach significance (p=0.1362/ p=0.0569). Non-hematological SAEs were another negative predictor for impaired OS and PFS (p=0.0054/ p=0.0021). In the follow-up performed at a median of 11 months after the first fitness assessment, the R-MCI improved or remained stable in 90% vs. deteriorated in only 10% of patients.
In conclusion, separation by R-MCI/frailty-defined subgroups was superior to age-based subgroups and can be used to improve tailored treatment. Fitter patients benefit from intensive therapies, whereas frail patients bear a need for initial DR.
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