Optimization of rituximab for the treatment of DLBCL
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Optimization of rituximab for the treatment of DLBCL : increasing the dose for elderly male patients. / Pfreundschuh, Michael; Murawski, Niels; Zeynalova, Samira; Ziepert, Marita; Loeffler, M; Hänel, Matthias; Dierlamm, Judith; Keller, Ulrich; Dreyling, Martin; Truemper, Lorenz; Frickhofen, Norbert; Hünerlitürkoglu, Ali-Nuri; Schmitz, Norbert; Pöschel, Viola; Rixecker, Tanja; Berdel, Christian; Rübe, Christian; Held, Gerhard; Zwick, Carsten.
In: BRIT J HAEMATOL, Vol. 179, No. 3, 11.2017, p. 410-420.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Optimization of rituximab for the treatment of DLBCL
T2 - increasing the dose for elderly male patients
AU - Pfreundschuh, Michael
AU - Murawski, Niels
AU - Zeynalova, Samira
AU - Ziepert, Marita
AU - Loeffler, M
AU - Hänel, Matthias
AU - Dierlamm, Judith
AU - Keller, Ulrich
AU - Dreyling, Martin
AU - Truemper, Lorenz
AU - Frickhofen, Norbert
AU - Hünerlitürkoglu, Ali-Nuri
AU - Schmitz, Norbert
AU - Pöschel, Viola
AU - Rixecker, Tanja
AU - Berdel, Christian
AU - Rübe, Christian
AU - Held, Gerhard
AU - Zwick, Carsten
N1 - © 2017 John Wiley & Sons Ltd.
PY - 2017/11
Y1 - 2017/11
N2 - Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2was not more toxic than 375 mg/m2rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.
AB - Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2was not more toxic than 375 mg/m2rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Cyclophosphamide
KW - Dose-Response Relationship, Drug
KW - Doxorubicin
KW - Drug Administration Schedule
KW - Female
KW - Humans
KW - Lymphoma, Large B-Cell, Diffuse
KW - Male
KW - Medication Adherence
KW - Middle Aged
KW - Neoplasm Staging
KW - Prednisone
KW - Prognosis
KW - Rituximab
KW - Sex Factors
KW - Survival Analysis
KW - Treatment Outcome
KW - Vincristine
KW - Journal Article
KW - Multicenter Study
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1111/bjh.14860
DO - 10.1111/bjh.14860
M3 - SCORING: Journal article
C2 - 28990173
VL - 179
SP - 410
EP - 420
JO - BRIT J HAEMATOL
JF - BRIT J HAEMATOL
SN - 0007-1048
IS - 3
ER -