Chronic lymphocytic leukemia

Effect of first-line treatment on second primary malignancies and Richter’s transformation in patients with CLL

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Abstract

This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter’s transformations (RTs) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N=191) or a RT (N=75). Solid tumors (N=115; 43.2% of all second neoplasias) appeared most frequently, followed by RTs (N=75; 28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1; P<0.001), male sex (HR 1.7; P=0.01), co-morbidities (HR 1.6; P=0.01) and number of subsequent treatments1 (HR 12.1; P<0.001) showed an independent adverse prognostic impact on SPM-free survival. Serum thymidine kinase>10 U/l at trial enrollment (HR 3.9; P=0.02), non-response to first-line treatment (HR 3.6; P<0.001) and number of subsequent treatments1 (HR 30.2; P<0.001) were independently associated with increased risk for RT.

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Acknowledgements

We wish to thank the patients and their treating physicians who participated in the trials. This work was presented in part at the 12th International Conference on Malignant Lymphoma (Palazzo dei Congressi, Lugano, Switzerland, 19–22 June 2013), at the 15th International Workshop on CLL (Maritim Hotel, Cologne, Germany, 9–11 September 2013) and at the Annual Meeting of the German, Austrian and Swiss Society of Hematology and Oncology (DGHO, ÖGHO, SGMO, SGH; Austria Center Vienna, Vienna, Austria, 18–22 October 2013). The CLL4, CLL5 and CLL2M trial were planned and conducted as investigator–initiated trials by the German Chronic Lymphocytic Leukemia Study Group (GCLLSG). They were supported by research grants from German Cancer Aid, Medac Schering Onkologie, F. Hoffmann-La Roche and Mundipharma. The CLL8 study was conducted as an investigator–initiated trial by the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) from 2003 to 2004 and afterwards sponsored by F. Hoffmann-La Roche.

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Correspondence to B Eichhorst.

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Competing interests

BE received honoraria from Roche and Mudipharma for educational presentations. BE declared advisory board membership for Roche and Mundipharma. BE received research grants form Roche and Mundipharma and travel grants from Mundipharma. CM received travel grants from Mundipharma. PL received travel grants from Janssen, Roche and Mundipharma. PC received travel grants from Roche, Mundipharma and Janssen. NP received honoraria from Novartis and travel grants from JazzPharma and Celgene. AE received travel grants from Roche. JvT received travel grants from Celgene and Roche, research funding by Roche and Janssen and honoraria by Janssen. GK received travel grants from Celgene. SS received honoraria from Roche for educational presentations. SS declared advisory board membership of Roche. SS received research grants from Roche. SS received travel grants from Roche. C-MW received honoraria from Roche and Mundipharma. C-MW declared advisory board membership of Roche and Mundipharma. C-MW received research grants from Roche and Mundipharma and travel grants from Roche and Mundipharma. LM declared advisory board membership of Roche. MR received honoraria from Roche for educational presentations. MR received travel grants from Roche. KF received travel grants from Roche. MH declared advisory board membership of Roche and Celgene. MH declared participation in speakers’ bureau from Roche, Celgene, Mundipharma and Janssen. MH received research grants from Roche, Celgene and Janssen. JB, AMF and TS declare no conflict of interest.

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Maurer, C., Langerbeins, P., Bahlo, J. et al. Effect of first-line treatment on second primary malignancies and Richter’s transformation in patients with CLL. Leukemia 30, 2019–2025 (2016) doi:10.1038/leu.2016.113

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