The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma

Cox, Maria Christina; Pelliccia, Sveva; Marcheselli, Luigi; Battistini, Roberta; Arcari, Annalisa; Borza, Paola Anticoli; Patti, Caterina; Casaroli, Ivana; Landro, Francesca Di; Napoli, Arianna Di; Fabbri, Francesca; Caridi, Matteo; Tafuri, Agostino; Bocci, Guido; Musuraca, Gerardo

doi:10.1007/s10637-019-00769-5

Cited by 12 publications

(21 citation statements)

References 52 publications

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“…One-hundred-fifty-eight DLBCL with an associated PP were identified: 102 had an IgM paraprotein (30 of these cases were already described) 13,21 Overall, 90/651(13.8%) patients, received less intensive treatment as R-miniCHOP 29 and other regimens 30,31 , 14/651(2%) received more intensive regimens, and 3/651(0.5%) from the REF group did not receive anti-CD20 antibody. Consolidative radiotherapy was administered to 9 (9%) IgMs, 14(24%) OP and 102 (21%) REF respectively (p=.005).…”

Section: Resultsmentioning

confidence: 99%

DLBCL with an associated IgM serum paraprotein (IgMs- DLBCL) has poor prognosis and frequent mutations in MYD88, CD79B and TP53 genes

Cox

Marcheselli

Scafetta

et al. 2022

Preprint

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PURPOUSE: to assess the clinicopathologic features of a poorly defined subset of diffuse large b-cell lymphoma, which is characterized by the secretion of an IgM paraprotein (IgMs-DLBCL). EXPERIMENTAL DESIGN: multicentre, retrospective, and comparative study to analyse with an integrated diagnostic approach the IgMs-DLBCL subset.RESULTS: Overall, 650 DLBCL were enrolled: 102 had an associated serum IgM and 56 other paraproteins (OP), the remaining 492 cases were the reference group (REF). IgMs-DLBCL were characterized by older age, advanced stage, dissemination to extra-nodal organs, elevated LDH and poor PS. As a result, the majority of IgMs had a high IPI, NCC-IPI and CNS-IPI score (p<.001).Furthermore, IgMs qualified as an independent prognostic factor in multivariate analysis for both PFS and OS (p<.001). Remarkably, the incidence of CNS involvement was higher in the IgMs compared to the OP and the REF subsets, respectively (p<.001). IgMs-DLBCL were characterized by: 1) prevalence of non-GCB/ABC-type; 2) frequent overexpression of BCL-2; 3) preferential IGVH4-34 gene usage; 4) MYD88 and TP53 mutations, both occurringin 30.8% of IgMs cases (95%CI, 14.3-51.8) CONCLUSION: Our study was carried out on the largest series of IgMs-DLBCL reported so far. This is a sizeable subset of DLBCL (7.9%, 95%CI, 5.9-10.5%),which is worth to detect at diagnosis. Remarkably, IgMs-DLBCL harbours features of a molecular subset that associate with a worse outcome. Indeed, more studies are necessary to fully understand the molecular pathogenesis of IgMs-DLBCL and the biological mechanisms leading to the high rate of CNS spreading.

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Section: Resultsmentioning

confidence: 99%

DLBCL with an associated IgM serum paraprotein (IgMs- DLBCL) has poor prognosis and frequent mutations in MYD88, CD79B and TP53 genes

Cox

Marcheselli

Scafetta

et al. 2022

Preprint

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“…24,25,34,40,42,44 The other 11 studies were all subgroup studies, and minimal age for inclusion ranged from 18 to 70. [20][21][22][23]26,[29][30][31][32][33]38,41 For Lu et al 18 study, patients were recruited from a geriatric hematology department, but data on a minimal age as an inclusion criteria were not available, and median age of patients was 86.…”

Section: Age Criteriamentioning

confidence: 99%

Impact of therapeutic management and geriatric evaluation on patient of eighty years and older with diffuse large B‐cell lymphoma on survival: A systematic review

Briand

Gérard

Gauthier

et al. 2021

European J of Haematology

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Diffuse large B cell lymphoma (DLBCL) represents 30%-40% of adult non-Hodgkin lymphoma (NHL). 1 DLBCL is a highly aggressive disease, with a limited life expectancy without treatment and a poor prognosis in case of relapse or refractory disease. 2 Its incidence increases with age, with a median age of 70 years at diagnosis. 1 Considering population aging, an increased incidence is expected within the next few years. 3 R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Oncovin, Prednisone) regimen is widely used as a first-line treatment for this

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“…Four Italian clinical centres prospectively collected data on PTCL patients treated with the DEVEC schedule (Ethical Approval no 4640). The mCHEMO has been planned with an induction and a deescalated maintenance phase, both being composed of six cycles going on 28 days, as already described [9]. All along the first cycle, patients were controlled weekly with medical examination and blood test.…”

Section: Patients and Therapeutic Schedulementioning

confidence: 99%

“…All along the first cycle, patients were controlled weekly with medical examination and blood test. In case of adverse reactions, chemotherapy was held until recovery and the next cycle begun at decreased doses of etoposide [9]. In subjects achieving less than complete response (CR), maintenance cycles were delivered alternating: (1) cyclophosphamide (CTX) 50 mg for 14 days/etoposide (ETO) 50 mg for 7 days and (2) CTX 50 mg for 14 days/ vinorelbine (VNR) 30 mg thrice a week 3 weeks on/1 week off, until progression or excessive toxicity.…”

Section: Patients and Therapeutic Schedulementioning

confidence: 99%

“…mCHEMO has complex pharmacodynamics including the anti-angiogenic and immune-mediated effects that lead to tumour dormancy [7], but also the direct impact on cancer cell proliferation [8]. Recently, we demonstrated that the all-oral metronomic schedule DEVEC [Deltacortene ® (prednisone), etoposide, vinorelbine, cyclophosphamide] could be successfully administered in diffuse large B cell lymphoma (DLBCL) patients [9]. The aim of the present study is to report on a series of elderly PTCL subjects, considered not fit for intravenous chemotherapy schedules, who were treated with DEVEC in four Italian centres.…”

Section: Introductionmentioning

confidence: 99%

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

Cox

Banchi

Pelliccia

et al. 2020

Cancer Chemother Pharmacol

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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.

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The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma

Cited by 12 publications

References 52 publications

DLBCL with an associated IgM serum paraprotein (IgMs- DLBCL) has poor prognosis and frequent mutations in MYD88, CD79B and TP53 genes

DLBCL with an associated IgM serum paraprotein (IgMs- DLBCL) has poor prognosis and frequent mutations in MYD88, CD79B and TP53 genes

Impact of therapeutic management and geriatric evaluation on patient of eighty years and older with diffuse large B‐cell lymphoma on survival: A systematic review

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

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