The Survival of Transplant Ineligible Multiple Myeloma Patients Treated with Bortezomib-Based Chemotherapy Is Affected By the Patient Fitness

Background

Frail patients who are in a poor perfomance status and have serious comorbidities or abnormal laboratory results comprise about one-third of the transplant ineligible multiple myeloma (MM). These patients, most of the cases, are excluded from the clinical studies. By far, the outcome of the real world data according to the patients' fitness in transplant ineligible MM patients is limited.

Method

Four hundred and fifteen patients with MM who have been treated with bortezomib, melphalan and prednisone (VMP) as a first-line treatment were retrospectively analyzed. 4 factors included into the frailty scores were Age, ECOG PS (Eastern cooperative group performance status), eGFR (estimated glomerular filtration rate), and number of comorbidities (heart disease, lung disease, liver disease, cerebrovascular disease, diabetes mellitus). These factors were di- or trichotomized by the reference of previously published papers and the meaningful cut-offs in our data. The points given to each variables were after the following criteria: Age < 70 (point 0), 70-79 (point 1), ≥ 80 (point 2); ECOG PS 0-2 (point 0), 3-4 (point 2); eGFR ≥ 60 mL/min/1.73 m² (point 0), < 60 mL/min/1.73 m² (point 1); comorbidity 0-1 (point 0) and ≥ 2 (point 1). Patients were further classified by frailty scores: fit (points 0-2), unfit (points 3-5) and frail (point 6).

Result

The median follow-up duration was 26.72 months (range 0.37 - 180.20 months). All of the factors including the Age ≥ 80, ECOG PS 3-4, eGFR < 60 mL/min/1.73 m², and comorbidity ≥ 2 statistically significant for overall survival (OS) by univariate analysis. In multivariate analysis, ECOG PS 3-4 and eGFR < 60 mL/min/1.73 m² remained statistically significant for OS and Age ≥ 80 was marginally significant for OS (Table 1). The response rates by the fit, unfit, and frail were as follows: 77.5% (148/191), 71.4% (55/77), and 0% (0/2) (P= 0.028). The 3-year overall survival rates by the frailty were 66%, 41%, and 0% in the fit, unfit or frail patients respectively and showed statistically significant difference (Figure 1 and Table 2, P= 0.000). The comparison of the frailty score with international staging system (ISS) and revised ISS (R-ISS) revealed statistical significance of all of the prognostic systems affecting OS by the univariate analyses but R-ISS and frailty score remained significantly affecting OS.

Conclusion

Unfit and frail patients showed a significant decrease in OS compared to fit patients. But there was no difference between the unfit and fit patients in terms of response rate in patients with transplant ineligible MM patients who have received bortezomib-containing regimen. Treatment of the unfit and frail patients needs more caution on toxicity management and appropriate dosing schedules to improve the survival outcome.

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