Abstract
The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycline‐containing regimen could predict DLBCL outcome independently from the IPI. We analyzed 223 white Caucasian DLBCL patients who completed at least four cycles of first‐line immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP). The ARDI was calculated by specially developed software in each individual patient, simultaneously with the chemotherapy prescription, which instantly revealed all causes of its decrease. The relevance of the ARDI for progression‐free/overall survival (PFS/OS) was evaluated. Prolonged intervals between cycles of immunochemotherapy—the most common cause of decreased ARDI (49.3%, 110/223)—were due to neutropenia (absolute neutrophil count <1.0 × 109/L) and infections. Reductions in cytostatic doses were observed in 19.7% (44/223) of patients, mainly as the consequence of cardiotoxicity (23/223, 10.3%). The OS varied significantly when the ARDI was >90% (P < 0.00001). Multivariate analysis confirmed that an ARDI>90% was an IPI‐independent predictor of prolonged PFS (HR = 0.31; 95%CI: 0.20‐0.47; P < 0.00001) and OS (HR = 0.32; 95%CI: 0.21‐0.48; P < 0.00001). With an analytic tool allowing real‐time ARDI assessment, it was possible to maintain an ARDI above 90% in 161 of 223 patients (72%). DLBCL patients with an ARDI >90% have significantly better outcome regardless of the IPI; therefore, our official recommendation is an adequate dose density through efficient neutropenia prophylaxis and cardiac protection.
Highlights
The CHOP chemotherapy regimen, consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone, remains the first‐line standard of care in diffuse large B‐cell lymphoma (DLBCL).[1]
The clinical characteristics and risk factor distribution were representative of DLBCL and comparable to those described in the literature (Table 1).[17,18]
Kaplan‐Meier curve analysis showed no significant difference in Overall survival (OS) between patients with average relative dose intensity (ARDI) 90%
Summary
The CHOP chemotherapy regimen, consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone, remains the first‐line standard of care in diffuse large B‐cell lymphoma (DLBCL).[1]. A correlation between the dose intensity and the therapeutic effect remains undefined.[3-7]. Dose intensity (DI) reflects the dose of the administered drug per unit of time (ie, expressed in mg/m2 per week). DI has been considered in the treatment of solid tumors, and recently, it was considered in lymphoma therapy.[8,9]. The relative dose intensity (RDI) expresses the amount of drug administered per unit of time compared to the planned amount of drug at the scheduled time. The intensity of the entire chemotherapy regimen is better defined by the average relative dose intensity (ARDI), which is a calculation of the mean values of the RDI of all drugs used in a chemotherapy cycle
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