The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia

Giovanni Del Poeta, Maria Ilaria Del Principe, Maria Antonietta Irno Consalvo, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Carla Mazzone, Antonio Bruno, Laura Gianni, Giovanni Capelli, Francesco Lo Coco, Maria Cantonetti, Valter Gattei, Sergio Amadori

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment. METHODS. The authors conducted a Phase II study, in which rituximab was added to fludarabine for patients with symptomatic, untreated CLL, to evaluate clinical outcomes. Sixty patients with B-CLL received 6 monthly courses of fludarabine (25 mg/m2 for 5 days) followed by 4 weekly doses of rituximab (375 mg/m2). RESULTS. On the basis of National Cancer Institute criteria, 47 of 60 patients (78%) achieved a complete remission, 9 of 60 patients (15%) achieved a partial remission, and 4 of 60 patients (7%) had no response or progressive disease. It is noteworthy that the patients experienced a long progression-free survival (PFS) from treatment (68% at 3 yrs). A significantly shorter PFS was observed in ZAP-70-positive patients (25% vs. 100% at 3 yrs; P = 0.00005), in CD38-positive patients (18% vs. 91% at 3 yrs; P = 0.0002), and in patients who had more minimal residual disease (36% vs. 77% at 2.5 yrs; P = 0.001). CONCLUSIONS. With the addition of rituximab to fludarabine, improved clinical outcomes were obtained, and the stratification of patients by using ZAP-70 and CD38 may help clinicians offer more aggressive and/or experimental approaches to the treatment of patients with high-risk B-CLL subtypes.

Original languageEnglish
Pages (from-to)2743-2752
Number of pages10
JournalCancer
Volume104
Issue number12
DOIs
Publication statusPublished - Dec 15 2005

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B-Cell Chronic Lymphocytic Leukemia
Disease-Free Survival
fludarabine
Rituximab
ZAP-70 Protein-Tyrosine Kinase
National Cancer Institute (U.S.)
Residual Neoplasm
Combination Drug Therapy
Monoclonal Antibodies
Clinical Trials

Keywords

  • B-cell chronic lymphocytic leukemia
  • CD38
  • Fludarabine
  • Minimal residual disease
  • Outcome
  • Response
  • Rituximab
  • Treatment
  • ZAP-70

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Del Poeta, G., Del Principe, M. I., Irno Consalvo, M. A., Maurillo, L., Buccisano, F., Venditti, A., ... Amadori, S. (2005). The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia. Cancer, 104(12), 2743-2752. https://doi.org/10.1002/cncr.21535

The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia. / Del Poeta, Giovanni; Del Principe, Maria Ilaria; Irno Consalvo, Maria Antonietta; Maurillo, Luca; Buccisano, Francesco; Venditti, Adriano; Mazzone, Carla; Bruno, Antonio; Gianni, Laura; Capelli, Giovanni; Lo Coco, Francesco; Cantonetti, Maria; Gattei, Valter; Amadori, Sergio.

In: Cancer, Vol. 104, No. 12, 15.12.2005, p. 2743-2752.

Research output: Contribution to journalArticle

Del Poeta, G, Del Principe, MI, Irno Consalvo, MA, Maurillo, L, Buccisano, F, Venditti, A, Mazzone, C, Bruno, A, Gianni, L, Capelli, G, Lo Coco, F, Cantonetti, M, Gattei, V & Amadori, S 2005, 'The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia', Cancer, vol. 104, no. 12, pp. 2743-2752. https://doi.org/10.1002/cncr.21535
Del Poeta G, Del Principe MI, Irno Consalvo MA, Maurillo L, Buccisano F, Venditti A et al. The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia. Cancer. 2005 Dec 15;104(12):2743-2752. https://doi.org/10.1002/cncr.21535
Del Poeta, Giovanni ; Del Principe, Maria Ilaria ; Irno Consalvo, Maria Antonietta ; Maurillo, Luca ; Buccisano, Francesco ; Venditti, Adriano ; Mazzone, Carla ; Bruno, Antonio ; Gianni, Laura ; Capelli, Giovanni ; Lo Coco, Francesco ; Cantonetti, Maria ; Gattei, Valter ; Amadori, Sergio. / The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia. In: Cancer. 2005 ; Vol. 104, No. 12. pp. 2743-2752.
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abstract = "BACKGROUND. Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment. METHODS. The authors conducted a Phase II study, in which rituximab was added to fludarabine for patients with symptomatic, untreated CLL, to evaluate clinical outcomes. Sixty patients with B-CLL received 6 monthly courses of fludarabine (25 mg/m2 for 5 days) followed by 4 weekly doses of rituximab (375 mg/m2). RESULTS. On the basis of National Cancer Institute criteria, 47 of 60 patients (78{\%}) achieved a complete remission, 9 of 60 patients (15{\%}) achieved a partial remission, and 4 of 60 patients (7{\%}) had no response or progressive disease. It is noteworthy that the patients experienced a long progression-free survival (PFS) from treatment (68{\%} at 3 yrs). A significantly shorter PFS was observed in ZAP-70-positive patients (25{\%} vs. 100{\%} at 3 yrs; P = 0.00005), in CD38-positive patients (18{\%} vs. 91{\%} at 3 yrs; P = 0.0002), and in patients who had more minimal residual disease (36{\%} vs. 77{\%} at 2.5 yrs; P = 0.001). CONCLUSIONS. With the addition of rituximab to fludarabine, improved clinical outcomes were obtained, and the stratification of patients by using ZAP-70 and CD38 may help clinicians offer more aggressive and/or experimental approaches to the treatment of patients with high-risk B-CLL subtypes.",
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T1 - The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia

AU - Del Poeta, Giovanni

AU - Del Principe, Maria Ilaria

AU - Irno Consalvo, Maria Antonietta

AU - Maurillo, Luca

AU - Buccisano, Francesco

AU - Venditti, Adriano

AU - Mazzone, Carla

AU - Bruno, Antonio

AU - Gianni, Laura

AU - Capelli, Giovanni

AU - Lo Coco, Francesco

AU - Cantonetti, Maria

AU - Gattei, Valter

AU - Amadori, Sergio

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N2 - BACKGROUND. Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment. METHODS. The authors conducted a Phase II study, in which rituximab was added to fludarabine for patients with symptomatic, untreated CLL, to evaluate clinical outcomes. Sixty patients with B-CLL received 6 monthly courses of fludarabine (25 mg/m2 for 5 days) followed by 4 weekly doses of rituximab (375 mg/m2). RESULTS. On the basis of National Cancer Institute criteria, 47 of 60 patients (78%) achieved a complete remission, 9 of 60 patients (15%) achieved a partial remission, and 4 of 60 patients (7%) had no response or progressive disease. It is noteworthy that the patients experienced a long progression-free survival (PFS) from treatment (68% at 3 yrs). A significantly shorter PFS was observed in ZAP-70-positive patients (25% vs. 100% at 3 yrs; P = 0.00005), in CD38-positive patients (18% vs. 91% at 3 yrs; P = 0.0002), and in patients who had more minimal residual disease (36% vs. 77% at 2.5 yrs; P = 0.001). CONCLUSIONS. With the addition of rituximab to fludarabine, improved clinical outcomes were obtained, and the stratification of patients by using ZAP-70 and CD38 may help clinicians offer more aggressive and/or experimental approaches to the treatment of patients with high-risk B-CLL subtypes.

AB - BACKGROUND. Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment. METHODS. The authors conducted a Phase II study, in which rituximab was added to fludarabine for patients with symptomatic, untreated CLL, to evaluate clinical outcomes. Sixty patients with B-CLL received 6 monthly courses of fludarabine (25 mg/m2 for 5 days) followed by 4 weekly doses of rituximab (375 mg/m2). RESULTS. On the basis of National Cancer Institute criteria, 47 of 60 patients (78%) achieved a complete remission, 9 of 60 patients (15%) achieved a partial remission, and 4 of 60 patients (7%) had no response or progressive disease. It is noteworthy that the patients experienced a long progression-free survival (PFS) from treatment (68% at 3 yrs). A significantly shorter PFS was observed in ZAP-70-positive patients (25% vs. 100% at 3 yrs; P = 0.00005), in CD38-positive patients (18% vs. 91% at 3 yrs; P = 0.0002), and in patients who had more minimal residual disease (36% vs. 77% at 2.5 yrs; P = 0.001). CONCLUSIONS. With the addition of rituximab to fludarabine, improved clinical outcomes were obtained, and the stratification of patients by using ZAP-70 and CD38 may help clinicians offer more aggressive and/or experimental approaches to the treatment of patients with high-risk B-CLL subtypes.

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KW - Response

KW - Rituximab

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KW - ZAP-70

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