Bortezomib plus <scp>EPOCH</scp> is effective as frontline treatment in patients with plasmablastic lymphoma

Castillo, Jorge J.; Guerrero‐Garcia, Thomas; Baldini, Francesco; Tchernonog, Emmanuelle; Cartron, Guillaume; Ninkovic, Slavisa; Cwynarski, Kate; Dierickx, Daan; Tousseyn, Thomas; Lansigan, Frederick; Linnik, Yevgeny; Mogollon, Renzo; Navarro, José Tomás; Olszewski, Adam J.; Reagan, John L.; Fedele, Pasquale; Gilbertson, Michael; Grigoriadis, George; Bibas, Michele

doi:10.1111/bjh.15156

Cited by 65 publications

(49 citation statements)

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“…25,26 A recently reported retrospective study of bortezomib combined with dose-adjusted EPOCH as upfront therapy similarly noted higher-than-expected response and survival rates in 6 cases of HIV-associated plasmablastic lymphoma. 27 Of note in the current study, lymphoma regression was observed in 1 patient with PEL after single-agent bortezomib administration, demonstrating activity of proteasome inhibition in this difficult-to-treat HAL subtype. Within our study, there was also a trend toward increased response and 1y-OS with increased bortezomib dose, further supporting the hypothesis that bortezomib adds to the activity of ICE/R.…”

Section: Discussionsupporting

confidence: 50%

Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas

et al. 2018

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Bortezomib combined with ICE/R is feasible and active in HIV 1 lymphomas with evidence of gammaherpesvirus lytic activation as hypothesized.• Bortezomib induced an increase in the anti-HIV cytidine deaminase APOBEC3G.HIV-associated lymphomas (HALs) have high rates of latent infection by gammaherpesviruses (GHVs). We hypothesized that proteasome inhibition would induce lytic activation of GHVs and inhibit HIV infectivity via preservation of cytidine deaminase APOBEC3G,improving lymphoma control. We tested this oncolytic and antiviral strategy by using bortezomib combined with ifosfamide, carboplatin, and etoposide (ICE) alone or with rituximab (ICE/R) in relapsed/refractory HAL. A 313 dose-escalation design was used with a 7-day lead-in period of single-agent bortezomib. Bortezomib was administered intravenously on days 1 and 8 of each cycle at 1 of 4 dose levels: 0.7, 1.0, 1.3, or 1.5 mg/m 2 . ICE began day 8 of cycle 1 and day 1 of subsequent cycles. Rituximab was included on day 1 of cycles 2 to 6 for CD20 1 lymphomas. Twenty-three patients were enrolled. The maximum tolerated dose of bortezomib was not reached. Grade 4 toxicities attributable to bortezomib were limited to myelosuppression. Responses occurred in 17 (77%) of 22 patients receiving any protocol therapy. The 1-year overall survival was 57%. After bortezomib alone, both patients with Kaposi sarcoma herpesvirus (KSHV)-positive lymphoma had more than a 1-log increase in KSHV viral load. In 12 patients with Epstein-Barr virus (EBV)-positive lymphoma, median values of EBV viral load increased. Undetectable HIV viremia at baseline in the majority of patients limited evaluation of HIV inhibition. APOBEC3G levels increased in 75% of evaluable patients. Bortezomib combined with ICE/R in patients with relapsed/refractory HAL is feasible with response and survival comparing favorably against previously reported secondline therapies. Changes in GHV viral loads and APOBEC3G levels trended as hypothesized. This trial was registered at www.clinicaltrials.gov as #NCT00598169.

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Section: Discussionsupporting

confidence: 50%

Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas

et al. 2018

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“…It was postulated that higher proportion of PBL in males can be explained by higher incidence of HIV in males compared to females 11 . The aggressive behavior of PBL was highlighted in prior small studies that reported median OS ranging from 7 to 62 months 3,8,9,11,21 . Many of these studies included both treated and untreated patients and it is well known that untreated PBL patients have a very short survival of several months only 9 .…”

Section: Discussionmentioning

confidence: 99%

“…Plasmablastic lymphoma is an aggressive lymphoma with overall survival (OS) ranging from 7 to 62 months, according to small retrospective studies 8‐12 . It is associated with HIV infection in 50% to 69% of patients 9,11 .…”

Section: Introductionmentioning

confidence: 99%

Survival analysis in treated plasmablastic lymphoma patients: a population‐based study

2020

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Herein we analyzed survival outcomes in chemotherapy-treated patients with plasmablastic lymphoma (PBL) diagnosed between 2010 to 2016 (n = 248). Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database (April 2019 release based on November 2018 submission). The majority of patients were male (81.9%) and younger than 60 years (71.0%). Oral and gastrointestinal (GI) sites were the most frequent primary extranodal locations (23% and 19.4%, respectively). Oral primary location was inversely associated with presence of B symptoms and advanced Ann-Arbor stage. The 3-year and 5-year overall survival (OS) rates of treated PBL patients were 54% (95% CI: 46.5%-60.8%) and 52.8% (95% CI: 45.2%-59.8%). Three-year conditional survival for 2-year and 3-year survivors were 90.3% and 97.8%, overlapping the survival of a general population matched by age, sex and calendar year. In a multivariable analysis, oral primary location was associated with not only better OS (HR 0.43; 95% CI: 0.21-0.88, P = .021) but also better lymphoma-specific survival (LSS) (SHR 0.36; 95% CI: 0.15-0.86, P = .022); age ≥60 years was associated with shorter LSS (SHR 1.73; 95% CI: 1.02-2.96, P = .043). Seven registries granted access to HIV status (n = 93) where HIV infection was detected in 52.7% of cases. The HIV status did not affect survival outcomes in unadjusted and adjusted analyses. We identified clinical characteristics associated with survival and showed that treated PBL patients may achieve long-term survival. 1 | INTRODUCTION Plasmablastic lymphoma (PBL) is a rare aggressive non-Hodgkin lymphoma with unknown incidence. Plasmablastic lymphoma was first described as a distinct clinicopathological entity in 1997 by Delecluse et al. and was shown to be associated with HIV infection (15 of 16 cases), Epstein-Barr virus (EBV) infection (9 of 16 cases) and a predilection for oral cavity, particularly jaw mucosa. 1 Subsequently, PBL was described in non-HIV patients with primary involvement outside of the oral cavity and was incorporated as a distinct clinical lymphoma type into the latest World Health Organization lymphoma classification. 2 It is considered to be a subtype of large B-cell lymphoma with plasmablastic morphology and expression of plasma cell markers (CD79a, CD38, CD138 and MUM-1), but lacking expression of B-cell markers (CD20, PAX-5). 3 The differential diagnosis includes immunoblastic diffuse large B-cell lymphoma, ALK positive diffuse large B-cell lymphoma, HHV-8 positive large B-cell lymphoma, primary effusion lymphoma, plasmablastic or anaplastic multiple myeloma and undifferentiated carcinoma. 3-5 Nodal involvement and association with HIV and EBV are typical for PBL but not seen in plasma cell neoplasms. 5-7 Plasmablastic lymphoma is an aggressive lymphoma with overall survival (OS) ranging from 7 to 62 months, according to small Jorge A. Florindez and Juan Pablo Alderuccio contributed equally to this study.

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“…As the PL cells are characterized by the expression of plasma cell transcription factors such as XBP1 and BLIMP1, bortezomib may work by targeting these factors, which may have an effect on antibody production and unfolded protein response . Bortezomib, in combination with DA‐EPOCH, has been reported to induce a complete remission rate of >90% (n = 16) and a 65% 5‐year overall survival in the frontline setting in a retrospective case series published in 2018 . A systematic review of bortezomib in plasmablastic lymphoma also reported that the overall response rate (ORR) to bortezomib‐based regimens was 100%, with complete remission (CR) in 89% of patients and a 2‐year overall survival rate of 55% …”

Section: Discussionmentioning

confidence: 99%

An unusual case of plasmablastic lymphoma presenting as dermatomyositis

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et al. 2020

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Bortezomib plus EPOCH is effective as frontline treatment in patients with plasmablastic lymphoma

Cited by 65 publications

References 10 publications

Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas

Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas

Survival analysis in treated plasmablastic lymphoma patients: a population‐based study

An unusual case of plasmablastic lymphoma presenting as dermatomyositis

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