scholarly journals Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions

2021 ◽  
Vol 11 ◽  
Author(s):  
Huan Chen ◽  
Tao Pan ◽  
Yizi He ◽  
Ruolan Zeng ◽  
Yajun Li ◽  
...  

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinicopathologic disease from other types of diffuse large B-cell lymphoma (DLBCL) with unique prognostic features and limited availability of clinical data. The current standard treatment for newly diagnosed PMBCL has long been dependent on a dose-intensive, dose-adjusted multi-agent chemotherapy regimen of rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Recent randomized trials have provided evidence that R-CHOP followed by consolidation radiotherapy (RT) is a valuable alternative option to first-line treatment. For recurrent/refractory PMBCL (rrPMBCL), new drugs such as pembrolizumab and CAR-T cell therapy have proven to be effective in a few studies. Positron emission tomography-computed tomography (PET-CT) is the preferred imaging modality of choice for the initial phase of lymphoma treatment and to assess response to treatment. In the future, baseline quantitative PET-CT can be used to predict prognosis in PMBCL. This review focuses on the pathology of PMBCL, underlying molecular basis, treatment options, radiotherapy, targeted therapies, and the potential role of PET-CT to guide treatment choices in this disease.

Author(s):  
M. Cortés Romera ◽  
C. Gámez Cenzano ◽  
A.P. Caresia Aróztegui ◽  
J. Martín-Comín ◽  
E. González-Barca ◽  
...  

2019 ◽  
Vol 12 (2) ◽  
pp. 595-602 ◽  
Author(s):  
Thomas Bemis ◽  
Jonathan Ioanitescu ◽  
Lynn Mackovick ◽  
Azzam Hammad ◽  
Jascha Rubin

Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous disease with a variety of chromosomal abnormalities contributing to differences in management. While it is known that Double Hit Lymphomas (DHL) warrant more aggressive chemotherapy regimens, debate remains on how to treat Double Expresser Lymphomas (DEL). We present a case of a DEL treated with an aggressive regimen of 2 alternating cycles of R-CODOX-M (rituximab, cyclophosphamide, doxorubicin, vincristine and methotrexate) and R-IVAC (rituximab, ifosfamide, etoposide and high dose cytarabine). The regimen resulted in a significant response to treatment with marked reduction in tumor size and avidity, and an acceptable side effect profile. There was, however, residual metabolic activity on repeat PET CT scan. After consolidation with 36 Grey radiotherapy, a PET CT demonstrated a complete metabolic response. Debate remains regarding treatment approaches in DEL. Our case supports the categorization of DEL alongside DHL as resistant lymphomas requiring a more aggressive regimen than standard therapy.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4580-4580
Author(s):  
Carolina Feres ◽  
Guilherme Fleury Perini ◽  
Carolina Leme de Moura Pereira ◽  
Larissa Lane Cardoso Teixeira ◽  
Mariana Nassif Kerbauy ◽  
...  

Abstract Introduction: About one third of patients with diffuse large B-cell lymphoma (DLBCL) fail frontline treatment or have early relapse. Baseline quantitative parameters derived from positron emission computed tomography (PET/CT) at baseline may predict outcome in DLBCL patients. However, their prognostic value in interim scans is unclear. Recently, the role delta maximum standardized uptake value (ΔSUVmax) has been tested as a predictor of PFS. In this retrospective study we aimed to analyze the role of ΔSUVmax between baseline and interim PET-CT as a predictor of progression of disease within 1 year in DLBCL patients and, to compare this parameter to the standard validated method to evaluate disease response: Deauville scale (DS). Methods: This is a single-center retrospective cohort study from São Paulo, Brazil. We included patients with DLBCL who had baseline (b-PET) and interim (i-PET, after 2-3 cycles of treatment) PET-CTs and who have been treated with 6 cycles of R-CHOP given every 21 days. All PET-CTs were analyzed by the same physician and blinded for the clinical features. Delta maximum standardized uptake value (ΔSUVmax) was calculated by the difference in % between initial PET SUVmax and iPET SUVmax. The objective was to assess if ΔSUV performed better than Deauville scale (DS) in predicting early disease progression. Cut-off values were defined by receiver operating characteristic (ROC) analysis. Analysis was performed with Cox model. Model comparison was based on the lowest AIC. Results: A total of 83 patients with DLBCL were available for analyses. The median age was 60 years and 66% of patients had a germinal center B-Cell (GCB) phenotype. With median follow-up of 15 months, patients with a cut-off ΔSUVmax <85% had a higher risk of disease relapse (49% vs 2%, p<0.001) at 12 months (figure 1). Patients with DS >3 in the iPET were also at a higher risk of disease progression (p<0.001) (figure 2). The model with ΔSUVmax was better adjusted (AIC=86) than the one with DS (AIC=92). The median maximum uptake at baseline PET/CT, MYC and/or BCl2 expression were not predictive of relapse at 12 months. International prognostic index (IPI) was also predictive of relapse (p=0.003), but again performed poorer than ΔSUVmax (AIC=99). Discussion/Conclusion: We showed that ΔSUVmax quantitative PET-CT model has superior discriminatory power than the qualitative DS model and the clinical IPI. Although we have a small sample, this finding corresponds with PETAL trial, which also showed that the ΔSUVmax method is superior to the commonly used Deauville five-point scale to identify patients at high risk of treatment fails. Although, the ΔSUVmax cut-off value calculated in our study was 85%, while in the PETAL study a reduction off 66% in the baseline SUV was the considered cutoff. Maybe, combing ΔSUVmax method in a with DS and IPI can improve prognostic stratification and early identification of high risk DLBCL. The ΔSUVmax is an easily reproducible method, that can be easily assessed by PET-CT, differing from other quantitative measures like the total metabolic tumor volume. In conclusion, further validation in a large sample of patients should be performed before the incorporation of quantitative PET-CT methods in clinical practice however it is a promising prognostic marker. Figure 1 Figure 1. Disclosures Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau.


Author(s):  
Xiaojuan Peng ◽  
Yutang Yao ◽  
Xiao Jiang ◽  
Xing Zhou ◽  
Chuan Li ◽  
...  

2021 ◽  
pp. 1-9
Author(s):  
François Allioux ◽  
Damaj Gandhi ◽  
Jean-Pierre Vilque ◽  
Cathy Nganoa ◽  
Anne-Claire Gac ◽  
...  

2017 ◽  
Vol 59 (5) ◽  
pp. 1195-1201 ◽  
Author(s):  
Allison Winter ◽  
Lisa Rybicki ◽  
Shetal N. Shah ◽  
Deepa Jagadeesh ◽  
Aaron T. Gerds ◽  
...  

2016 ◽  
Vol 71 (3) ◽  
pp. 280-286 ◽  
Author(s):  
S.H. Kwon ◽  
D.R. Kang ◽  
J. Kim ◽  
J.-K. Yoon ◽  
S.J. Lee ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Rasha Haggag ◽  
Naglaa A. Mostafa ◽  
Marwa Nabil ◽  
Hala A. Shokralla ◽  
Neveen F. H. Sidhom

Background: The aim of this study was to investigate the prognostic role of mammalian target of Rapamycin (mTOR) and C-X-C chemokine receptor type 4 (CXCR4) in diffuse large-B-cell lymphoma (DLBCL) patients.Patients and methods: This retrospective study was collected data from 64 de novo DLBCL patients, who received standardized R-CHOP therapy at two oncology centers. CXCR4 and mTOR expressions were assessed by immunohistochemistry.Results: Out of the 64 DLBCL patients, 40 patients were positive for CXCR4 (62.5%) and 35 patients for mTOR (54.7%) expressions. CXCR4 expression was positively correlated with mTOR expression (r = 0.7; p < .001). While mTOR expression was significantly associated with high lactate dehydrogenase level (p = .03) and number of extranodal sites one or more (p =.02), CXCR4 expression was significantly associated with high IPI score (p < .001) and ECOG PS (p = .005). Furthermore, theexpression levels of mTOR and CXCR4 were significantly associated with older ages and poor response to treatment (p = .04, <.001 and .04, .03, respectively). After a median Follow up of 22 months, mean ± SD overall survival (OS) was 65.391 ± 4.705. Kaplan–Meier analysis showed that patients positive for mTOR and CXCR4 expression had shorter DFS (p = .01 & .02) and OS (p = .02 & .04). Multivariate analysis showed that CXCR4 and mTOR positivity is an independent prognostic factor for significantly poorer DFS (p = .03, and .02 respectively) but not for OS (p = .09 and .08 respectively) in the DLBCL pateints.Conclusion: Our results indicate that the expression of CXCR4 and mTOR may be poor prognostic biomarkers in DLBCL.


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