Prognostic Value of PINI in Elderly Patients with Multiple Myeloma (MM).

The Prognostic Inflammatory and Nutritional Index (PINI) is a simple scoring system which aggregates two blood markers of inflammatory (C reactive protein and orosomucoid) and of nutritional (albumin and prealbumin) states. This marker is predictive of nearest lethality and chronic institutionalization in geriatric routine practice for hospitalized elderly patients. MM is a malignant plasma cell disorder with a median age around 70 years old at diagnosis, a population characterized with several comorbid conditions that indirectly determine the prognosis and the treatment decision. The current most powerful adverse prognostic markers in MM are the adverse karyotypic abnormalities, such as 17p deletion and (4;14) translocation, and the high serum beta-2 microglobulin (b2m) that corresponds to the high International Staging System (ISS) group in combination with albumin. However, approximately 70% of MM patients have no know adverse karyotypic abnormalities, and high b2m and ISS are essentially informative for a minority of patients. We have sought to evaluate the prognostic value of PINI in MM in a large retrospective study.

The PINI score was determined in 226 previously untreated MM patients from sera collected at diagnosis before treatment, of whom 112 pts were 65 or older. The Serum albumin, prealbumin, orosomucoid (human α1-acid glycoprotein) and hsCRP were measured by immunonephelometry. PINI is calculated with the following formula: PINI=[orosomucoid (mg/L) × CRP (mg/L)]/[albumin (g/L) × prealbumin (mg/L)]. To avoid inadequate value of CRP, patients with fever and documented infection at diagnosis were excluded from the study.

Main patients characteristics at sample collection for the overall population were as follows: median age=64, ISS 2 and 3 of 29% and 21%, respectively. 35% of pts had chromosome 13 deletion (del13q). These characteristics were similar in pts older than 65. With a median follow-up of 57 months, median (+/-se) overall survival (OS) were 57 (+/-7) and 40 (+/-5) months in the overall and elderly population, respectively. The median (min-max) value of PINI were 0,29 (0,01-123) and 0,47 (0,01-123), respectively. The most informative PINI cut-off was determined at 4 and corresponded to its best impact on survival; 14% and 12.5% of pts had PINI ≥ 4, in the overall and elderly population, respectively. PINI correlated with markers of tumour burden such as high b2m level, low hemoglobin level and, high creatinin value. PINI ≥ 4 was also related to high ISS score (II + III), in 46% and 32% of pts, respectively. PINI did not correlate to del13q. In univariate analysis, median OS (+/-se) was significantly lower in patients with PINI ≥ 4 (number of death/number of pts in the group (O/N)=24/31) than pts with PINI <4 (O/N=99/195), 26 (±12) vs. 65 (±7) months, [p=0.0003; OR=2.21] respectively. This adverse prognostic impact was even more dramatic in elderly patients, 6 (±7) months (O/N=14/112) vs. 45 (±7) months (O/N=60/96), p<0.0001, respectively. Other markers, age above 65, low haemoglobin value below 10g/dL, b2m above 4mg/L, presence of del13q and ISS score II +III remained significant but with a lower impact. Interestingly, PINI ≥ 4 identified a subgroup of patients characterized with intermediate prognostic in pts with low b2m (< 4 mg/L) [PINI ≥ 4: O/N=8/12, 50 (±29) vs. PINI <4: O/N=53/123, 79 (±6), p=0.02], hemoglobin value ≥ 10g/dL [PINI ≥ 4: O/N=9/12, 13 (±10) vs. PINI <4: O/N=54/135, 79 (±8), p=0.0003] and absence of del13q [PINI ≥ 4: O/N=10/15, 50 (±18) vs. PINI <4: O/N=36/86, 80 (±13), p=0.0018]. In multivariate analysis, factors evaluated for association with high PINI were age (>65years), hemoglobin (<10g/dL), platelet count (<100 ×10⁹/L), b2M (≥4mg/L) and ISS (II+III). Modeling results showed a significant association of PINI with elevated b2M and del13q, with 51% (17/33) vs. 72% (16/22) of patients with high PINI in b2M < 4 mg/L vs. ≥ 4 mg/L (OR=2.4, p=0.003), and with 56% (34/60) vs. 85% (6/7) of patients with high PINI in absence vs. presence of del13q (OR=2.3, p=0.001).

PINI appeared to be a useful and easy-to-perform marker in routine practice to determine the prognosis of patients with MM, especially in the elderly population with no know adverse karyotypic abnormalities and low b2m/ISS. The study of PINI should be performed in future prospective clinical trials to validate these results.

No relevant conflicts of interest to declare.