The current standard treatment for diffuse large B-cell lymphoma (DLBCL) is Rituximab-CHOP (cyclophosphamide (CPM), doxorubicin(DXR), vincristine(VCR), prednisolone). It is well known that VCR causes peripheral neuropathy and is often dose-reduced or omitted from the treatment. Whether the omission of VCR from 1 or more cycles of therapy could jeopardize the survival of patients with DLBCL has not yet been adequately addressed. Our study aimed to investigate any differences in progression free (PFS) and overall (OS) survival in R-CHOP treated patients with DLBCL between those with omission of VCR or not.
In this Swedish multi-institutional, retrospective, cohort study we included all adult patients diagnosed with and primarily treated for DLBCL or subgroups of high-grade malignant B-cell lymphoma with either R-CHOP/CHOEP (CHOP plus Etoposide) or mini-CHOP (dose-reduced), between 2000-2013. All information on patients’ characteristics, treatment outcome, and survival was extracted from the in-hospital computer based systems. Any clinical variables significantly associated with PFS or OS in univariate analysis by the log-rank test were considered for entry into a multivariate Cox proportional hazard regression model. Omission of VCR was included in all models as an independent variable of interest. All statistical analyses were performed with IBM SPSS statistics version 22.
In total 541 patients were included in the study cohort. In 95 (17.6%) patients, VCR was omitted due to toxicity. The omission was more often decided during the last 3 cycles of chemotherapy (86 patients, 90.5%). Univariate analysis revealed 9 potential prognostic factors associated with PFS and 10 with OS. Omission of VCR was not associated with either PFS or OS in both univariate and multivariate analyses (HR for PFS: 1.21, 95% Confidence Interval (CI) 0.76-1.95; HR for OS; 1.12, 95% CI 0.75-1.69). For PFS only advanced stage at diagnosis was found to be significantly associated with worse outcome (p = 0.047). In respect of OS kidney/adrenal involvement (p = 0.014), Doxorubicin –RelativeDoseIntensity 2
Omission of VCR does not affect either PFS or OS in patients with DLBCL treated with R-CHOP/CHOEP. As a result, clinicians can safely decide to omit VCR in case of severe neurotoxicity due to VCR. Considering the association of bulky disease and kidney/adrenal manifestation of lymphoma on survival, further studies should focus on whether the treatment options for these subgroups need to be individualized. Finally, clinicians should be aware of the importance of giving adequate dose of DXR during treatment given the growing body of evidence on the role of dose intensity on survival.
Clinical trial identification
Legal entity responsible for the study
Centre for Clinical research Sörmland, Uppsala university
All authors have declared no conflicts of interest.