All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma

Abstract

Purpose Peripheral T cell lymphomas (PTCLs) have an overall poor prognosis. Indeed, registry data in elderly patients show that the median progression-free survival (mPFS) following first-and second-line therapies are only 6.7 and 3.1 months, respectively. The aim of the study is to show the activity of metronomic chemotherapy, a regular administration of low chemotherapeutic drug doses allowing a favourable toxicity profile, on elderly PTCL patients. Methods We report a series of 17 PTCL patients, treated with the all-oral metronomic schedule DEVEC (prednisoloneetoposide-vinorelbine-cyclophosphamide) in four Italian centres. Patients 5/17 (29.4%) were treatment-naïve (naïve) and 12/17 (70.6%) were relapsed-refractory (RR), respectively. The median age was 83 years (range 71-87) and 71.5 years (range 56-85) for naïve and RR, respectively. In vitro activity of metronomic vinorelbine (VNR), etoposide (ETO) and their concomitant combination on HH, a PTCL cell line, was also assessed. Results Histology: PTCL-not-otherwise-specified = 12; angioimmunoblastic = 2; NK/T nasal type = 1; adult-type leukaemia lymphoma = 1, transformed Mycosis Fungoides = 1. The overall response rate was 80 and 58% in naïve and RR, respectively; whereas the PFS was 20 in naïve (95% CI 0-43) and 11 months (95% CI 4.2-17.8) in RR. The occurrence of relevant adverse events was 23.5%, which was managed with ETO dose reduction. In vitro experiments showed that both metronomic VNR and ETO caused a significant inhibitory activity on HH cells and a strong synergism when administered concomitantly. Conclusion All-oral DEVEC showed an encouraging activity and acceptable toxicity. This schedule deserves further studies in elderly PTCL also for assessing combinations with targeted drugs.

Complete Remission of a Diffuse Large B-Cell Lymphoma in a Young Patient, with Severe Tuberous Sclerosis, Treated with Metronomic Chemotherapy and Ibrutinib: A Case Report

“…Noteworthy, the R-DEVEC schedule was extremely effective and well tolerated. This effect was not surprising because the DEVEC metronomic regimen +/− rituximab demonstrated encouraging results in treatment-naïve and R/R frail, elderly subjects, with B and T-cell aggressive NHL [13‒16]. Moreover, AYAs with DLBCL have shown excellent outcomes when treated with regimens developed for adults, such as R-CHO(E)P [19], confirming the possibility to adopt a schedule tested for older subjects also for our young patient.…”

“…The major advantages of mCHEMO are the multiple mechanisms of action [10], the easiness to combine with target therapies [11], the low toxicity, the oral administration, and, therefore, the feasibility of a more comfortable, home-based treatment [12]. The all-oral metronomic schedule DEVEC, including vinorelbine, cyclophosphamide, etoposide, and prednisone +/− rituximab, showed very promising results in treatmentnai €ve and relapsed/refractory (R/R) elderly subjects, with B and T-cell aggressive NHL compared with a real-life setting of patients treated with systemic chemotherapy [13][14][15][16].…”

Remarkable Remission Rate and Long-Term Efficacy of Upfront Metronomic Chemotherapy in Elderly and Frail Patients, with Diffuse Large B-Cell Lymphoma

“…Also, G-CSF should be scheduled in all patients from day 21. Worthy of note, peripheral neuropathy, which is an insidious long-term side effect of iv-CHEMO containing vinca-alkaloids, such as R-mini-CHOP, never occurred in patients treated with DEVEC [ 15 , 17 ]. Both high IPI and EPI scores, which were prevalent in this series, had a poor prognostic impact, while the presence of a bulky mass did not achieve statistical significance.…”

“…The assay was performed as previously described [ 15 ] with minor modifications. OCI-LY3 cells were exposed for 144 h with metronomic VNR (0.001–10 nM) and ETO (0.025–100 nM), or with vehicle alone.…”

“…The CI and DRI indexes were estimated by the CalcuSyn v.2.0 software (Biosoft, Cambridge, UK). Furthermore, the synergistic, additive, and antagonistic effect of the drug combination was also mapped with the Loewe additivity model, using the Combenefit software (v.2.021) [ 15 ].…”