Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia - PubMed (original) (raw)

Clinical Trial

. 2007 Jan 15;109(2):405-11.

doi: 10.1182/blood-2006-07-033274. Epub 2006 Sep 28.

Susan M Geyer, Timothy G Call, Tait D Shanafelt, Clive S Zent, Diane F Jelinek, Renee Tschumper, Nancy D Bone, Gordon W Dewald, Thomas S Lin, Nyla A Heerema, Lisa Smith, Michael R Grever, John C Byrd

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Clinical Trial

Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia

Neil E Kay et al. Blood. 2007.

Abstract

Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (>70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1

Figure 1

The time to NCI Working Group 96 response between patients enrolled at site 1 versus site 2.

Figure 2

Figure 2

Time to progression in relation to NCI Working Group 96 response criteria. CR indicates complete remission; NPR, nodular partial remission; PR, partial remission.

Figure 3

Figure 3

PFS by CD5+/CD19+ levels. Difference in the 2 curves was significant at P < .001.

Figure 4

Figure 4

PFS by del(11q22.3) versus other FISH cohorts. There was no significant difference in PFS between the 2 CLL cohorts.

Figure 5

Figure 5

PFS by age cutoff of 70 years. There was no significant difference in PFS between the 2 age cohorts.

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