Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

Plinabulin and Pegfilgrastim in Combination for the Prevention of Chemotherapy-Induced Neutropenia in Patients with Breast Cancer (PROTECTIVE-2): A Randomized Trial

PurposePlinabulin is a non-granulocyte colony-stimulating factor (G-CSF) novel small molecule with both anticancer and myeloprotective effects. Single-agent plinabulin is myeloprotective in the first week of the chemotherapy cycle, and pegfilgrastim in the second week. We assessed the efficacy and safety of the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) following chemotherapy.MethodsThis randomized, open-label, Phase 2 trial enrolled patients with breast cancer. All received docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 on Day 1. In the combined therapy cohort, patients received plinabulin 20 mg/m2 on Day 1 and 1.5, 3, or 6 mg pegfilgrastim on Day 2. The primary objective was to establish the recommended Phase 3 dose (RP3D). Secondary endpoints included absolute neutrophil count (ANC) nadir, relative dose intensity (RDI), and incidence of adverse events including neutropenia and bone pain.ResultsIn total, 115 patients were randomized and evaluated. The combination therapy at the RP3D (plinabulin 20 mg/m2 and pegfilgrastim 6 mg) was well-tolerated and had superior CIN prevention in terms of Grade 4 and Grade 3/4 neutropenia frequency, absolute neutrophil count (ANC) nadir, higher relative dose intensity (RDI), less bone pain, and less toxicity burden when compared with pegfilgrastim 6 mg alone.ConclusionPlinabulin combined with pegfilgrastim at the RP3D (plinabulin 20 mg/m2 Day 1 and pegfilgrastim 6 mg Day 2) had more favorable efficacy, safety, and tolerability profiles and lower bone pain incidence than did pegfilgrastim alone.Trial information Clinical Trial Registration: ClinicalTrials.gov NCT04227990Date registered: January 14, 2020 Retrospectively registered

Impact of Pegfilgrastim Approval on Relative Dose Intensity and Outcomes of R-CHOP for Diffuse Large B-Cell Lymphoma

Maintaining the relative dose intensity (RDI) of chemotherapy with R-CHOP improves the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim was approved for use in Japan in November 2014 to prevent febrile neutropenia (FN) and maintain RDI. We herein reviewed 334 patients with DLBCL who received six or more courses of R-CHOP and retrospectively analyzed the difference in the RDI, overall survival (OS), and progression-free survival (PFS) between patients whose treatment started after November 2014 (the post-approval group) and those whose treatment started before October 2014 (the pre-approval group). The incidence of FN was lower (39.2% vs. 62.2%, P < 0.001) and the RDI of R-CHOP was higher (86.8% vs. 67.8%, P < 0.001) in the post-approval group. The RDI of patients aged < 70 years was maintained at a high level even if their RDI was predicted to be low based on the model derived from the pre-approval group. Pegfilgrastim was administered to many of these patients and was thought to have contributed to the high RDI maintenance in the post-approval group. The 5-year OS (85.7% and 69.9%, P = 0.009) and PFS (81.4% and 64.4%, P = 0.011) were superior in the post-approval group. In this group, improved survival outcomes were observed among patients with Ann Arbor stage 3/4 (5-year OS: 83.7% vs. 61.3%, P = 0.019) and high risk on the NCCN-IPI (5-year OS: 80.7% vs. 32.4%, P = 0.014). Maintenance of high RDI of R-CHOP and significant improvement in clinical outcomes, especially in high-risk groups, were observed after pegfilgrastim approval.