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Outcomes after first-line immunochemotherapy for primary mediastinal B-cell lymphoma: a LYSA study.

ABSTRACT: Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.

SUBMITTER: Camus V

PROVIDER: S-EPMC8679665 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Primary mediastinal B-Cell lymphoma (PMBL) is a recently defined entity comprising ~2-10% non-Hodgkin lymphomas (NHL). Unlike most NHL subtypes, PMBL lacks recurrent gene rearrangements to serve as biomarkers or betray target genes. While druggable, late chemotherapeutic complications warrant the search for new targets and models. Well characterized tumor cell lines provide unlimited material to serve as preclinical resources for verifiable analyses directed at the discovery of new biomarkers and pathological targets using high throughput microarray technologies. The same cells may then be used to seek intelligent therapies directed at clinically validated targets. Four cell lines have emerged as potential PMBL models: FARAGE, KARPAS-1106P, MEDB-1 and U-2940. Transcriptionally, PMBL cell lines cluster near c(lassical)-HL and B-NHL examples showing they are related but separate entities. Here we document genomic alterations therein, by cytogenetics and high density oligonucleotide/SNP microarrays and parse their impact by integrated global expression profiling. PMBL cell lines were distinguished by moderate chromosome rearrangement levels undercutting cHL, while lacking oncogene translocations seen in B-NHL. In total 61 deletions were shared by two or more cell lines, together with 12 amplifications (?4x) and 72 homozygous regions. Integrated genomic and transcriptional profiling showed deletions to be the most important class of chromosome rearrangement. Lesions were mapped to several loci associated with PMBL, e.g. 2p15 (REL/COMMD1), 9p24 (JAK2, CD274), 16p13 (SOCS1, LITAF, CIITA); plus new or tenuously associated loci: 2p16 (MSH6), 6q23 (TNFAIP3), 9p22 (CDKN2A/B), 20p12 (PTPN1). Discrete homozygous regions sometimes substituted focal deletions accompanied by gene silencing implying a role for epigenetic or mutational inactivation. Genomic amplifications increasing gene expression or gene-activating rearrangements were respectively rare or absent. Our findings highlight biallelic deletions as a major class of chromosomal lesion in PMBL cell lines, while endorsing the latter as preclinical models for hunting and testing new biomarkers and actionable targets.

Project description:PurposeExcellent outcomes obtained after infusional dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-EPOCH) alone have led some to question the role of consolidative radiation therapy (RT) in the treatment of primary mediastinal B cell lymphoma (PMBL). We reviewed the outcomes in patients treated with 1 of 3 rituximab-containing regimens (cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone [R-HCVAD], or R-EPOCH) with or without RT. We also evaluated the ability of positron emission tomography-computed tomography (PET-CT) to identify patients at risk of relapse.Methods and materialsWe retrospectively identified 97 patients with diagnoses of stage I/II PMBCL treated at our institution between 2001 and 2013. The clinical characteristics, treatment outcomes, and toxicity were assessed. We analyzed whether postchemotherapy PET-CT could identify patients at risk for progressive disease according to a 5 point scale (5PS) Deauville score assigned.ResultsAmong 97 patients (median follow-up time, 57 months), the 5-year overall survival rate was 99%. Of patients treated with R-CHOP, 99% received RT; R-HCVAD, 82%; and R-EPOCH, 36%. Of 68 patients with evaluable end-of-chemotherapy PET-CT scans, 62% had a positive scan (avidity above that of the mediastinal blood pool [Deauville 5PS = 3]), but only 9 patients experienced relapse (n=1) or progressive disease (n=8), all with a 5PS of 4 to 5. Of the 25 patients who received R-EPOCH, 4 experienced progression, all with 5PS of 4 to 5; salvage therapy (RT and autologous stem cell transplantation) was successful in all cases.ConclusionCombined modality immunochemotherapy and RT is well tolerated and effective for treatment of PMBCL. A postchemotherapy 5PS of 4 to 5, rather than 3 to 5, can identify patients at high risk of progression who should be considered for therapy beyond chemotherapy alone after R-EPOCH.

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Outcomes after first-line immunochemotherapy for primary mediastinal B-cell lymphoma: a LYSA study.

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