Beta-2 microglobulin (B2M) is an independent prognostic factor for clinical outcomes in patients with CLL treated with frontline fludarabine, cyclophosphamide, and rituximab (FCR) regardless of age, creatinine clearance (CrCl)

Abstract

7034 Introduction: High β2M levels are a risk factor in CLL. PCR therapy has been reported to be better tolerated than FCR in older or with decrease renal function pts (Shanafelt, Blood 108:15a). We assessed the association between age, CrCl, PS, β2M and outcomes in pts treated with FCR. Methods: From 7/99 to 1/04, 300 pts received rituximab 375 mg/m2 D1; fludarabine 25 mg/m2/d D2–3; and cyclophosphamide 250 mg/m2/d D2–3. Serum β2M levels were measured by radioimmunoassay. CrCl was calculated (Cockcroft-Gault equation). Results: The median age was 57 yrs (≥70, 14%). Age ≥70 was associated with fewer FCR courses (p<.0001); lower rates of CR (p=.001), overall response (OR; p=.04), survival (OS; p<.0001), and FFS (p=.008); and higher rates of G3–4 thrombopenia (p<.0001) or anemia (p=.002) compared with age<70. The median CrCl was 90 mL/min (CrCl <70, 27%). Pts with CrCl <70 had higher rates of G3–4 thrombopenia (p=.006) or anemia (p=.01) than others. There were no differences between the 2 groups in the other outcomes. PS was 0 in 40%, 1 in 57%, and 2 in 3% of pts. Better PS was associated with higher rates of CR (p=.007) and FFS (p=.02) but did not affect OR or OS. The median β2M level was 3.7 mg/L (β2M ≥ 4, 43%). The rates of CR, survival, and FFS were lower in pts with β2M ≥ 4 compared with others (p<.0001 each). High β2M levels were associated with older age, lower CrCl levels, poorer PS (p<.0001 each), higher rates of G3–4 neutropenia (p=.005), thrombocytopenia (p=.01), and infections (p=.03), and fewer FCR courses (p=.004). The median follow-up was 5 yrs. The rates of CR, 3-yr OS and 3-yr FFS were 72%, 87% and 76%, respectively. Independent factors predicting response were lower β2M (p=.0004) and lower WBC counts (p=.02). Independent factors predicting longer OS were younger age (p=.001), lower β2M (p=.003) and lower WBC (p=.03). Independent factors predicting longer FFS were lower β2M levels (p=.0006), and lower WBC counts (p=.005). Conclusion: Age ≥70 yrs and poor PS, but not CrCl level were associated with poor clinical outcomes. High β2M levels are an independent adverse prognostic factor for CR, OS, and FFS in the context of other prognostic factors. No significant financial relationships to disclose.