The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients

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.

Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity

“…Early studies in NHL patients treated with an anthracycline-containing induction regimen showed that 28% of patients had an RDI <70%, which was associated with a decreased response rate and shorter overall 2-year survival [5]. Similar findings have been reported in more recent studies with the rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen, noting poor survival associated with RDI of less than 50-90% (Table 1) [47][48][49][50].…”

Higher average chemotherapy dose intensity improves prognosis in patients with aggressive adult T‐cell leukemia/lymphoma

“…The DI of chemotherapy affects the prognosis of malignant diseases, and in DLBCL, a reduced ARDI of R‐CHOP was associated with poor prognosis 11‐15 . A relatively high median ARDI of CHOP for the treatment of DLBCL has been observed in clinical practice 14,21 ; in a nationwide study from the United States, for example, the median ARDI was 83%, and the DI was less than 45% in only 5% of patients 22 . In contrast, the median ARDI in aggressive ATL patients who received intensive chemotherapies was only 60% in our study.…”

“…10 The DI of chemotherapy affects the prognosis of malignant diseases, and in DLBCL, a reduced ARDI of R-CHOP was associated with poor prognosis. [11][12][13][14][15] A relatively high median ARDI of CHOP for the treatment of DLBCL has been observed in clinical practice 14,21 ;…”

“…10 The relative DI (RDI) of chemotherapy affects the prognosis of malignant diseases, including diffuse large B-cell lymphoma (DLBCL). The RDI indicates the drug dose administered per unit of time compared to the planned drug dose to be administered at the scheduled time, and a study on DLBCL treatment reported a relationship between survival and the RDI of rituximab (R)-CHOP [11][12][13][14][15] ; however, the effect of RDI on ATL has never been reported.…”

Early chemotherapy de-escalation strategy in advanced-stage Hodgkin lymphoma patients with negative positron emission tomography scan after two escalated BEACOPP cycles

“…The average relative dose intensity of the entire treatment was 91%, which was above the recently recommended 90% in lymphoma therapy. 24 Overall, 35 of the 188 patients (19%) required at least one dose reduction during treatment with escBEACOPP; in 29 cases, bleomycin and vincristine infusion was omitted on the eighth day of treatment because of neutropenia. In ABVD regimen, no We did not formally assess fertility, but it should be noted that 48 pregnancies have been reported after completion of therapy (28 women and the wives of 20 male patients).…”