Impact of rituximab and radiotherapy on outcome of patients with aggressive B-cell lymphoma and skeletal involvement.
OBJECTIVE
To study clinical presentation, outcome, and the role of radiotherapy in patients with aggressive B-cell lymphoma and skeletal involvement treated with and without rituximab.


METHODS
Outcome of patients with skeletal involvement was analyzed in a retrospective study of nine consecutive prospective trials of the German High-Grade Non-Hodgkin lymphoma Study Group.


RESULTS
Of 3,840 patients, 292 (7.6%) had skeletal involvement. In the MabThera International Trial (MInT) for young good-prognosis patients and the Rituximab With CHOP Over 60 Years (RICOVER-60) study for elderly patients, the randomized addition of rituximab improved event-free survival (EFS; hazard ratio for MInT [HRMInT] = 0.4, P > 001; hazard ratio for RICOVER-60 [HRRICOVER-60] = 0.6, P > .001) and overall survival (OS; HRMInT = 0.4, P < .001; HRRICOVER-60 = 0.7, P = .002) in patients without skeletal involvement, but failed to improve the outcome of patients with skeletal involvement (EFS: HRMInT = 1.4, P = .444; HRRICOVER-60 = 0.8, P = .449; OS: HRMInT = 0.6, P = .449; HRRICOVER-60 = 1.0, P = .935). Skeletal involvement was associated with a worse outcome after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (HREFS = 1.5, P = .048; HROS = 1.1; P = .828), but not after CHOP without rituximab (HREFS = 0.8, P = .181; HROS = 0.7, P = .083). In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a decreased risk (HREFS = 0.3, P = .001; HROS = 0.5; P = .111).


CONCLUSIONS
Rituximab failed to improve the outcome of patients with diffuse large B-cell lymphoma with skeletal involvement, although our data suggest a beneficial effect of radiotherapy to sites of skeletal involvement. Whether radiotherapy to sites of skeletal involvement can be spared in cases with a negative positron emission tomography after immunochemotherapy should be addressed in appropriately designed prospective trials.
Gerhard Held, Niels Murawski, Jochen Fleckenstein, Christian Rübe, and Michael Pfreundschuh, Saarland University Medical School; Bertram Glass and Norbert Schmitz, Asklepios-Klinik St. Georg, Hamburg; Samira Zeynalova and Marita Ziepert, Leipzig University, Leipzig; Barbara Kempf, Klinikum Landshut, Landshut; Andreas Viardot, Universitätsklinikum Ulm, Ulm; Martin Dreyling, Ludwig-Maximilian University, Munich; Michael Hallek, Cologne University, Cologne; and Mathias Witzens-Harig, Heidelberg University, Heidelberg, Germany.
Gerhard
G
Held
Samira
S
Zeynalova
Niels
N
Murawski
Marita
M
Ziepert
Barbara
B
Kempf
Andreas
A
Viardot
Martin
M
Dreyling
Michael
M
Hallek
Mathias
M
Witzens-Harig
Jochen
J
Fleckenstein
Christian
C
Rübe
Carsten
C
Zwick
Bertram
B
Glass
Norbert
N
Schmitz
Michael
M
Pfreundschuh
D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab