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

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Relevance of the immunoglobulin VH somatic mutation status in patients with

chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and

rituximab (FCR) or related chemoimmunotherapy regimens.

I Lin, Constantine S Tam, J Keating, G Wierda,

O'Brien, Lerner, R Coombes, Ellen Schlette, Alessandra Ferrajoli,

Lynn L Barron, J Kipps, Rassenti, Stefan Faderl, Hagop Kantarjian,

and Lynne V Abruzzo

Blood, December 2, 2008; .

Leukemia Department, The University of Texas MD Cancer Center, Houston,

TX, United States.

Although immunoglobulin VH mutation status (IgVH-MS) is prognostic in CLL

patients treated with alkylating agents or single-agent fludarabine, its

significance in the era of chemoimmunotherapy is not known. We determined the

IgVH somatic mutation status in 177 patients enrolled in a phase II study of

fludarabine, cyclophosphamide and rituximab (FCR), and in 127 patients treated

with subsequent chemoimmunotherapy protocols. IgVH-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 IgVH than those whose CLL used mutated IgVH (TTP

47% vs 82% at 6 years, p<0.001). In a multivariate model considering all

baseline characteristics, IgVH-MS emerged as the only determinant of remission

duration (hazard ratio 3.8, p<0.001). Our results suggest that post-remission

interventions should be targeted towards patients with unmutated IgVH status.

PMID: 19050308