Relevance of the Immunoglobulin v_H somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens

Although immunoglobulin V_H mutation status (IgV_H MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgV_H somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgV_H MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgV_H than those whose CLL used mutated IgV_H (TTP 47% vs 82% at 6 years, P < .001). In a multivariate model considering all baseline characteristics, IgV_H MS emerged as the only determinant of remission duration (hazard ratio 3.8, P < .001). Our results suggest that postre-mission interventions should be targeted toward patients with unmutated IgV_H status.