AUTHORS
Mathias Rummel, Tobias Arnold, MD2, Christina Balser3, Bernd Hertenstein4, Christian Buske, MD5, Christian Lerchenmüller6, Michael Koenigsmann7, Elisabeth Lange8, Manfred Reeb9, Ulrich Kaiser10, Jan Dürig11, Tobias Gaska, MD12, Wolfgang Blau13, Richard Greil, Prof.14, Jürgen Barth15
AFFILIATIONS
1 University Clinic Giessen, Giessen, Germany
2 University Clinic Giessen, Giessen, Germany
3 Private prectice, Marburg, Germany
4 Klinikum Bremen Mitte, Bremen, Germany
5 University Clinic Ulm, Ulm, Germany
6 Private prectice, Münster, Germany
7 Private prectice, hannover, Germany
8 Evangelisches Krankenhaus Hamm, Hamm, Germany
9 Private prectice, Kaiserslautern, Germany
10 St. Bernwald Hospital, Hildesheim, Germany
11 University Clinic, Essen, Germany
12 Brüderkrankehaus St Josef, Paderborn, Germany
13 Helios Dr. Horst Schmidt Kliniken Wiesbaden GmbH, Wiesbaden, Germany
14 Paracelsus Medical University, Salzburg, Austria
15 University Clinic Giessen, Giessen, Germany
ABSTRACT
Background: R-maintenance for 2 years is part of a standard treatment approach for previously untreated follicular lymphoma. In this study we compared the efficacy and safety of 4 versus 2 years of R-maintenance following first-line treatment with B-R.
Methods: Patients included in the study were required to have stage II (bulky disease >7 cm), III, or IV disease. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rates, overall survival (OS), and toxicity. Patients were treated with up to 6 cycles of B-R plus 2 additional cycles of Rituximab. All responding patients received 2 years R-maintenance (375 mg/m2 every 2 months). Patients who tolerated treatment for the entire 2 years and who were still in remission hereafter were subsequently randomized to 2 more years of R-maintenance or observation.
Results: The study enrolled 612 patients with follicular lymphoma. Of those, 555 were evaluable for response and 497 (90%) responded to B-R induction, with 181 patients (33%) achieving a complete remission. Overall, 261 patients discontinued treatment during induction or within the first 2 years of R-maintenance. The most frequent reasons for discontinuation included progression in 85 of 261 pts (33%), patient’s or doctor’s choice in 55 pts (21%), toxicity or infections in 29 pts (11%), Rituximab intolerance in 14 pts (5%), or death in 11 pts (4%) with a median age of 70 years and of those 5 pts dying from infections. There were 351 patients randomized to 2-years or 4-years of R-maintenance (n = 172 and n = 178, respectively). The median age was 61 years and patient characteristics were comparable between groups. The median observation time was 130 months following randomization. Median PFS and OS were not reached in either arm. PFS at 10 years appeared numerically superior for 4-years versus 2-years of R-maintenance with a 10-year PFS rate of 74% vs. 69%, respectively; however this difference was not statistically significant (hazard ratio 0.82, 95% CI 0.55 – 1.22, p = 0.324). In addition, no significant difference in overall survival (OS) was observed between the 4-years and 2-years groups of R maintenance, with a median 10-year OS-rate of 84% and 87%, respectively (hazard ratio 01.12, 95% CI 0.64 – 1.98, p = 0.682). One patient died from a PML (randomized to 4 years of Rituximab). Updated results on late toxicities will be presented at the ASH meeting.
Conclusions: Prolonged R-maintenance of 4-years did not provide a benefit over the standard of 2-years R-maintenance after first-line induction treatment with B-R. Treatment with B-R followed by 2 years of R-maintenance resulted in long-term disease control, with 69% of patients remaining progression-free at 10 years.
DISCLOSURES
Mathias Rummel: No relevant conflicts of interest to declare.