Patients with chronic lymphocytic leukemia with high-risk genomic features have inferior outcome on successive Cancer and Leukemia Group B trials with alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101

Abstract

Alemtuzumab consolidation has been investigated to improve remission duration after fludarabine-based induction for chronic lymphocytic leukemia (CLL). The impact on genomic high-risk disease remains unknown. Cancer and Leukemia Group B (CALGB) 19901 and 10101 enrolled previously untreated patients to receive alemtuzumab consolidation after fludarabine-based induction. Immunoglobulin heavy chain gene (IGVH) mutation status and interphase cytogenetics were assessed retrospectively. Treatment response with these alemtuzumab-containing regimens was similar, regardless of genomic risk, except for patients harboring del(17p), where few complete remissions were observed. Progression-free survival (PFS) was similar between IGVH groups, but overall survival (OS) was inferior in IGVH unmutated patients (p = 0.03). Cytogenetic risk group was associated with PFS and OS (p = 0.01 for both), with similarly short PFS in patients with del(17p) and del(11q) and particularly short OS in patients with del(17p). Cytogenetic risk group remained significantly associated with PFS and OS when controlling for other prognostic factors (PFS: p = 0.009; OS: p = 0.02), as did the negative association of IGVH unmutated disease with OS (p = 0.004). Results were similar when restricting to patients who received at least one dose of alemtuzumab consolidation, demonstrating limited ability to overcome the poor outcome associated with high-risk genetic features.

Trial registration: ClinicalTrials.gov NCT00004857 NCT00098670.

Figures

Figure 1A

Kaplan-Meier estimates of progression-free survival (PFS) by immunoglobulin heavy chain variable region (IGVH) mutational status (unmutated = solid line, mutated = dashed line).

Figure 1B

Kaplan-Meier estimates of overall survival (OS) by IGVH mutational status (unmutated = solid line, mutated = dashed line).

Figure 1C

Kaplan-Meier estimates of progression-free survival (PFS) by immunoglobulin heavy chain variable region (IGVH) mutational status (unmutated = solid line, mutated = dashed line) in patients receiving alemtuzumab consolidation.

Figure 1D

Kaplan-Meier estimates of overall survival (OS) by IGVH mutational status (unmutated = solid line, mutated = dashed line) in patients receiving alemtuzumab consolidation.

Figure 2A

Kaplan-Meier estimates of PFS by cytogenetic risk group [del(17p13.1) = solid line, del(11q22.3) = dashed line, Not del(17p13.1)/del(11q22.3) = dotted line].

Figure 2B

Kaplan-Meier estimates of OS by cytogenetic risk group [del(17p13.1) = solid line, del(11q22.3) = dashed line, Not del(17p13.1)/del(11q22.3) = dotted line].

Figure 2C

Kaplan-Meier estimates of PFS by cytogenetic risk group [del(17p13.1) = solid line, del(11q22.3) = dashed line, Not del(17p13.1)/del(11q22.3) = dotted line] in patients receiving alemtuzumab consolidation.

Figure 2D

Kaplan-Meier estimates of OS by cytogenetic risk group [del(17p13.1) = solid line, del(11q22.3) = dashed line, Not del(17p13.1)/del(11q22.3) = dotted line] in patients receiving alemtuzumab consolidation.

Figure 3A

Kaplan-Meier estimates of progression-free survival (PFS) according to availability of genetic risk stratification data: none, FISH only, both IGVH and FISH, IGVH only.

Figure 3B

Kaplan-Meier estimates of overall survival (OS) according to availability of genetic risk stratification data: none, FISH only, both IGVH and FISH, IGVH only.