Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study

Francesc Bosch, Guy Cantin, Agostino Cortelezzi, Wolfgang Knauf, Mourad Tiab, Mehmet Turgut, Andrey Zaritskey, Jean Louis Merot, Eugen Tausch, Kerstin Trunzer, Susan Robson, Ekaterina Gresko, Sebastian Böttcher, Robin Foà, Stephan Stilgenbauer, Véronique Leblond

Research output: Contribution to journalArticle

Abstract

GREEN (NCT01905943) is a nonrandomized, open-label, single-arm, phase 3b study investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in chronic lymphocytic leukemia (CLL). We report the preplanned subgroup analysis of 140 previously untreated, fit CLL patients who received obinutuzumab plus fludarabine and cyclophosphamide (G-FC). The primary endpoint was safety and tolerability. Efficacy was the secondary endpoint. Obinutuzumab 1000 mg was administered intravenously on Day (D)1 (dose split D1‒2), D8 and D15 of Cycle (C)1, and D1 of C2–6 (28-day cycles). Standard intravenous/oral doses of fludarabine and cyclophosphamide were administered on D1–3 of C1–6. Overall, 87.1% of patients experienced grade ≥ 3 adverse events (AEs), including neutropenia (67.1%) and thrombocytopenia (17.1%). Serious AEs were experienced by 42.1% of patients. Rates of grade ≥ 3 infusion-related reactions and infections were 19.3% and 15.7%, respectively. Overall response rate was observed in 90.0%, with 46.4% of patients achieving complete response (CR; including CR with incomplete marrow recovery). Minimal residual disease negativity rates were 64.3% in peripheral blood and 35.7% in bone marrow (intent-to-treat analysis). After a median observation time of 25.6 months, 2 year progression-free survival was 91%. Frontline G-FC represents a promising treatment option for fit patients with CLL.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusAccepted/In press - Jan 1 2019

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B-Cell Chronic Lymphocytic Leukemia
Cyclophosphamide
Bone Marrow
Safety
Residual Neoplasm
Combination Drug Therapy
Neutropenia
Thrombocytopenia
Disease-Free Survival
Observation
fludarabine
obinutuzumab
Infection

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia : a subgroup analysis of the GREEN study. / Bosch, Francesc; Cantin, Guy; Cortelezzi, Agostino; Knauf, Wolfgang; Tiab, Mourad; Turgut, Mehmet; Zaritskey, Andrey; Merot, Jean Louis; Tausch, Eugen; Trunzer, Kerstin; Robson, Susan; Gresko, Ekaterina; Böttcher, Sebastian; Foà, Robin; Stilgenbauer, Stephan; Leblond, Véronique.

In: Leukemia, 01.01.2019.

Research output: Contribution to journalArticle

Bosch, F, Cantin, G, Cortelezzi, A, Knauf, W, Tiab, M, Turgut, M, Zaritskey, A, Merot, JL, Tausch, E, Trunzer, K, Robson, S, Gresko, E, Böttcher, S, Foà, R, Stilgenbauer, S & Leblond, V 2019, 'Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia: a subgroup analysis of the GREEN study', Leukemia. https://doi.org/10.1038/s41375-019-0554-1
Bosch, Francesc ; Cantin, Guy ; Cortelezzi, Agostino ; Knauf, Wolfgang ; Tiab, Mourad ; Turgut, Mehmet ; Zaritskey, Andrey ; Merot, Jean Louis ; Tausch, Eugen ; Trunzer, Kerstin ; Robson, Susan ; Gresko, Ekaterina ; Böttcher, Sebastian ; Foà, Robin ; Stilgenbauer, Stephan ; Leblond, Véronique. / Obinutuzumab plus fludarabine and cyclophosphamide in previously untreated, fit patients with chronic lymphocytic leukemia : a subgroup analysis of the GREEN study. In: Leukemia. 2019.
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abstract = "GREEN (NCT01905943) is a nonrandomized, open-label, single-arm, phase 3b study investigating the safety and efficacy of obinutuzumab alone or in combination with chemotherapy in chronic lymphocytic leukemia (CLL). We report the preplanned subgroup analysis of 140 previously untreated, fit CLL patients who received obinutuzumab plus fludarabine and cyclophosphamide (G-FC). The primary endpoint was safety and tolerability. Efficacy was the secondary endpoint. Obinutuzumab 1000 mg was administered intravenously on Day (D)1 (dose split D1‒2), D8 and D15 of Cycle (C)1, and D1 of C2–6 (28-day cycles). Standard intravenous/oral doses of fludarabine and cyclophosphamide were administered on D1–3 of C1–6. Overall, 87.1{\%} of patients experienced grade ≥ 3 adverse events (AEs), including neutropenia (67.1{\%}) and thrombocytopenia (17.1{\%}). Serious AEs were experienced by 42.1{\%} of patients. Rates of grade ≥ 3 infusion-related reactions and infections were 19.3{\%} and 15.7{\%}, respectively. Overall response rate was observed in 90.0{\%}, with 46.4{\%} of patients achieving complete response (CR; including CR with incomplete marrow recovery). Minimal residual disease negativity rates were 64.3{\%} in peripheral blood and 35.7{\%} in bone marrow (intent-to-treat analysis). After a median observation time of 25.6 months, 2 year progression-free survival was 91{\%}. Frontline G-FC represents a promising treatment option for fit patients with CLL.",
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AU - Cortelezzi, Agostino

AU - Knauf, Wolfgang

AU - Tiab, Mourad

AU - Turgut, Mehmet

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AU - Merot, Jean Louis

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AU - Trunzer, Kerstin

AU - Robson, Susan

AU - Gresko, Ekaterina

AU - Böttcher, Sebastian

AU - Foà, Robin

AU - Stilgenbauer, Stephan

AU - Leblond, Véronique

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