Prognostic impact of RDI of vincristine in patients with DLBCL receiving R-CHOP: a supplementary analysis of JCOG0601

Takahiro Nakashima , Tomotaka Suzuki , Ryunosuke Machida , Kazuyuki Shimada , Tsutomu Kobayashi , Dai Maruyama , Wataru Munakata , Shinsuke Iida , Ken Ohmachi , Tomohiro Kinoshita , Kiyoshi Ando , Hirokazu Nagai
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Abstract

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine [VCR], and prednisolone) is the standard of care for previously untreated patients with diffuse large B-cell lymphoma (DLBCL). However, some DLBCL survivors experience long-lasting VCR-related peripheral neuropathy (PN). VCR dose is usually reduced based on PN severity, but inconsistent results have been reported regarding the effect of VCR dose reduction on the prognosis of patients with DLBCL. To evaluate the clinical impact of the relative dose intensity (RDI) of VCR (RDIO), we conducted a supplementary analysis of JCOG0601, a randomized phase 2/3 trial in which R-CHOP and CHOP with 8 doses of weekly rituximab were compared for progression-free survival (PFS). Among 422 patients enrolled in JCOG0601, 401 who had received at least 6 courses of protocol treatment were eligible. PFS was not significantly different between patients with low RDIO (<95% [n = 161]) and high RDIO (≥95% [n = 240]; P = .0679), although those with low RDIO tended to have poor PFS (3-year PFS, 83.7% vs 78.2%). Multivariable analysis revealed that the presence of B symptoms and high-intermediate or high International Prognostic Index (IPI) risk, but not RDIO, were associated with poor PFS. To our knowledge, this is the first study revealing VCR dose reduction may not be associated with poor PFS as much as the presence of B symptoms and high-intermediate or high IPI risk, using data from a prospective trial with rituximab plus 21-day cycles of CHOP. If the patients with DLBCL can complete rituximab plus CHOP treatment, VCR dose reduction due to toxicity may not significantly impair treatment efficacy. JCOG0601 was registered at www.jcog.jp/en/trials as #jRCTs031180139.
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