Abstract
Standard first-line treatment of aggressive B cell lymphoma comprises six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus eight doses of rituximab (R). Whether adding two doses of rituximab to six cycles of R-CHOP is of therapeutic benefit has not been systematically investigated. The Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial investigated the ability of [18F]-fluorodesoxyglucose PET scanning to guide treatment in aggressive non-Hodgkin lymphomas. Patients with B cell lymphomas and a negative interim scan received six cycles of R-CHOP with or without two extra doses of rituximab. For reasons related to trial design, only about a third underwent randomization between the two options. Combining randomized and non-randomized patients enabled subgroup analyses for diffuse large B cell lymphoma (DLBCL; n = 544), primary mediastinal B cell lymphoma (PMBCL; n = 37), and follicular lymphoma (FL) grade 3 (n = 35). With a median follow-up of 52 months, increasing the number of rituximab administrations failed to improve outcome. A non-significant trend for improved event-free survival was seen in DLBCL high-risk patients, as defined by the International Prognostic Index, while inferior survival was observed in female patients below the age of 60 years. Long-term outcome in PMBCL was excellent. Differences between FL grade 3a and FL grade 3b were not apparent. The results were confirmed in a Cox proportional hazard regression model and a propensity score matching analysis. In conclusion, adding two doses of rituximab to six cycles of R-CHOP did not improve outcome in patients with aggressive B cell lymphomas and a fast metabolic treatment response.
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Acknowledgements
We thank the patients, investigators, and PET centers from all parts of Germany for their participation.
Funding
This work was funded by Deutsche Krebshilfe (grant nos. 107592 and 110515 to Ulrich Dührsen), Amgen Germany, and Roche Pharma (institutional research funding to the University Hospital Essen).
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Andreas Hüttmann: honoraria from Bristol-Myers Squibb, Takeda, Celgene, and Roche; travel reimbursement from Gilead and Amgen; Stefan P. Müller: institutional research funding from BTG Interventional Medicine; Frank Kroschinsky: honoraria and travel reimbursement from and consultancy for Roche, Celgene, Gilead, Pfizer, and Janssen; Paul La Rosée: honoraria and travel reimbursement from and consultancy for Roche; Martin Grieshammer: honoraria from, consultancy for, and speaker’s bureau of Roche, Amgen, AOP, Novartis, Shire, and Janssen; Georg Maschmeyer: honoraria from Gilead, Pfizer, Merck Serono, Celgene, Bristol-Myers Squibb, and Boehringer Ingelheim; consultancy for Gilead; travel reimbursement from Bristol-Myers Squibb; Ingo Brink: honoraria from Siemens and Rotop; travel reimbursement from Bayer; Tobias Gaska: institutional research funding from Roche; travel reimbursement from Ipsen; Aristoteles Giagounidis: consultancy for Celgene; Matthias Grube: consultancy for Bristol-Myers Squibb and Sanofi; Claudia Ose: institutional research funding, honoraria, and travel reimbursement from Medice Arzneimittel Pütter; Jan Dürig: honoraria from and consultancy for Roche and Amgen; Wolfram Klapper: institutional research funding from Roche, Amgen, Regeneron, Novartis, and Takeda; Ulrich Dührsen: institutional research funding and honoraria from Roche and Amgen.
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Hüttmann, A., Rekowski, J., Müller, S.P. et al. Six versus eight doses of rituximab in patients with aggressive B cell lymphoma receiving six cycles of CHOP: results from the “Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas” (PETAL) trial. Ann Hematol 98, 897–907 (2019). https://doi.org/10.1007/s00277-018-3578-0
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DOI: https://doi.org/10.1007/s00277-018-3578-0