Characteristics and Treatment Outcomes of Plasmablastic Lymphoma in British Columbia (BC)
Authors: Chien Nicole , Villa Diego , Freeman Ciara L. , Slack Graham W. , Savage Kerry J. , Scott David W. , Sehn Laurie H. , Song Kevin W , Gerrie Alina S. 
Published: November 2020

Introduction
Plasmablastic lymphoma (PBL) is a rare entity of aggressive large B-cell lymphoma initially described in HIV positive (pos) patients (pts) but subsequently also in immunocompetent pts. Due to its rarity and aggressiveness, there is no standard of care therapy. The published literature suggests CHOP chemotherapy is suboptimal. The role of bortezomib (BTZ) and more intensive therapies including consolidative stem cell transplant (SCT) remain uncertain. We aim to review the clinical characteristics and outcomes of pts with PBL in a population-based cohort from BC, Canada.
Methods
All pts diagnosed from Jan. 1997 - Oct. 2019 with histologically confirmed PBL using central pathology review were included. Baseline demographic, clinical and outcome data were retrospectively collected from the BC Cancer Lymphoid Cancer Database and medical records.
Results
42 pts were diagnosed with PBL during this period, including 15 (36%) HIV pos pts and 9 (21%) receiving chronic immunosuppression (CIS) for autoimmune disorders or renal transplant. Median age at diagnosis was 56 years (y) (range, 23-94 y) with ECOG performance status ≥3 in 26% (10/39 pts), elevated lactate dehydrogenase in 50% (20/40), EBER positive in 84% (32/38), and advanced disease defined by Ann Arbor stage 3-4, B symptoms and/or mass ≥ 10 cm in 69% (29/42). 37 pts (88%) had extranodal involvement; most common sites in order of frequency were oro/nasopharynx, bone, gastrointestinal and lung.
10/15 HIV pos pts were not on highly active antiretroviral therapy (HAART) at diagnosis. All but one were started on HAART after diagnosis. 8/9 pts receiving CIS had a dose reduction at diagnosis. 31 pts (11 HIV pos, 12 HIV negative, 8 CIS) received curative intent chemotherapy: 29 CHOP, 2 CEOP, and 5 had BTZ added/in place of vincristine. 3 pts had a consolidative autologous SCT (autoSCT) upfront. 10 pts, median age 77 y (range 38-94 y), had palliative therapy (single agent chemotherapy or radiation) due to poor performance status and/or comorbidities. An additional pt achieved complete response after HAART, then relapsed 19 months (mos) later, treated with CHOP but had further relapse and died of disease.
Median follow-up of living pts was 19 mos (range, 4-170). For pts treated with curative intent (N=31), 13/31 pts (42%) remain alive and in remission. 4 were refractory to first line chemotherapy, of which 3 were HIV pos. Only 2 of the refractory pts were fit for salvage therapy but did not respond and died of disease. 9 pts relapsed at a median of 15 mos (range, 8-50) from diagnosis, including 2/3 pts who received upfront consolidative autoSCT. 6/9 relapsed pts received salvage chemotherapy, generally with GDP. 1 pt died from early treatment toxicity. The other 5 pts were considered for SCT but 2 were ineligible due to progressive disease or comorbidities. Overall, 3 pts underwent consolidative SCT at relapse but 2 pts relapsed again within 6 mos of autoSCT. An additional pt is undergoing allogeneic SCT for relapse, 43 mos post upfront autoSCT. There was no difference in relapse rate according to HIV status (44% HIV negative vs 40% HIV pos, P=.63), however pts receiving CIS appeared to have a lower relapse, although not statistically significant (33%, P=.25).
At last follow-up, 18 pts have died: 12 from PBL (4 refractory, 8 relapsed); 4 from treatment complications during/within 3 mos of therapy (infection 2, myocardial infarction 2); 1 had comorbidities and tolerated first line therapy poorly, therefore elected for medical assistance in dying; 1 died in remission of an unrelated cause.
For the entire cohort, 1 y PFS and OS were 47% (95% CI, 39-55%) and 51% (95% CI, 43-59%) respectively, Fig. 1. There was no significant difference according to immune status (P=.87 for PFS and P=.72 for OS), Fig 2. Only 1/13 pts who relapsed remains in remission, 1 mo after allogeneic SCT.
Conclusion
This is one of the largest reviews of PBL pts reported. Our results confirm that PBL is a highly aggressive lymphoma with a low cure rate with current therapies and no difference in outcome according to immune status. We do not have adequate numbers to demonstrate additional benefit of BTZ or SCT. Nearly all pts who relapsed after upfront therapy died of disease. Further research is needed to understand the molecular mechanisms underlying the pathogenesis of PBL and to identify treatment strategies that will improve patient outcomes.

Disclosures
Villa: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; AZ: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria; Nano String: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Sandoz Canada: Consultancy, Honoraria; Immunovaccine: Consultancy, Honoraria; Purdue Pharma: Consultancy, Honoraria. Savage:Abbvie: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Servier: Consultancy; Takeda: Honoraria; Verastem: Honoraria. Scott:Abbvie: Consultancy; AstraZeneca: Consultancy; NIH: Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America.; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoString, Research Funding; Celgene: Consultancy. Sehn:Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Chugai: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria. Song:Celgene, Janssen, Amgen, Takeda: Honoraria; Celgene: Research Funding. Gerrie:Astrazeneca: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Sandoz: Consultancy.