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

2022; Multidisciplinary Digital Publishing Institute; Volume: 11; Issue: 23 Linguagem: Inglês

10.3390/jcm11237162

2077-0383

Guido Bocci, Sabrina Pelliccia, Paola Orlandi, Matteo Caridi, Marta Banchi, Gerardo Musuraca, Arianna Di Napoli, Maria Paola Bianchi, Caterina Patti, Paola Anticoli‐Borza, Roberta Battistini, Ivana Casaroli, Tiziana Lanzolla, Agostino Tafuri, Maria Christina Cox,

CAR-T cell therapy research

The upfront treatment of very elderly and frail patients with diffuse large B-cell lymphoma (DLBCL) is still a matter of debate. Herein, we report results of the metronomic all-oral DEVEC [prednisolone/deltacortene®, vinorelbine (VNR), etoposide (ETO), cyclophosphamide] combined with i.v. rituximab (R). This schedule was administered as a first line therapy in 22 elderly/frail DLBCL subjects (median age = 84.5 years). In 17/22 (77%) patients, the Elderly-IPI-score was high. After a median follow-up of 24 months, 15 patients had died: seven (50%) for causes unrelated to DLBCL or its treatment, six (40%) for progression, and two (13%) for multiorgan failure. Six treatment-pertinent serious-adverse-events occurred. At the end of induction, 14/22 (64%) achieved complete remission; overall survival and event-free survival at 24 months were both 54% (95% CI = 32−72%), while the time to progression was 74% (95% CI = 48−88%). Furthermore, antiproliferative and proapoptotic assays were performed on DLBCL/OCI-LY3 cell-line using metronomic VNR and ETO and their combination. Both metronomic VNR and ETO had concentration-dependent antiproliferative (IC50 = 0.036 ± 0.01 nM and 7.9 ± 3.6 nM, respectively), and proapoptotic activities in DLBCL cells. Co-administration of the two drugs showed a strong synergism (combination index < 1 and dose reduction index > 1) against cell proliferation and survival. This low-dose schedule seems to compare favourably with intravenous-CHEMO protocols used in the same subset. Indeed, the high synergism shown by metronomic VRN+ETO in in vitro studies, explains the remarkable clinical responses and it allows significant dose reductions.