There is no established standard treatment for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are not eligible to receive an intensive treatment. The combination of ...rituximab gemcitabine and oxaliplatin (R-GemOx) is widely used in this population but data are scarce. We retrospectively collected the data of 196 patients with R/R DLBCL treated with R-GemOx in two French centers over a period of 15 years. The median age of the population was 72 years (range, 24-89), 63% of the patients had an international prognostic index of 3 or higher and 57% were refractory to the last treatment. At the end of R-GemOx treatment, 33% of the patients obtained a complete response. The median progression-free survival (PFS) of the population was 5 months and the median overall survival (OS) was 10 months. Several factors were predictors of unfavorable survival: age over 75 years, international prognostic index of 2 or higher, refractory disease and de novo DLBCL. The median PFS and OS of the patients who obtained a complete response were 22 months and 40 months, respectively. The most significant toxicities were grade 3-4 hematological toxicities (31% of patients). Given its efficacy and tolerability, R-GemOx can be used in patients ineligible for intensive treatment and serve as a basis for new regimen combinations.
Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic ...genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.
This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.
Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (6763-71 years vs 7670-79 years, p < .001), age at first cardiac symptom (6661-71 years vs 7468-78 years, p < .001) and age at first extracardiac symptom (5952-70 years vs 6962-75 years, p = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (7167-74 vs 7876-79 years, p = .018).
This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.
Background Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the ...prevalence and prognostic impact of AS among patients with CA. Methods and Results We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) 1.09–3.64; ATTRv: SRR, 3.41; 95%CI 1.64–4.60; ATTRwt: SRR, 10.8; 95%CI 5.25–14.53). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI 0.56–1.14; ATTRv: SRR, 1.27; 95%CI 0.85–1.44; ATTRwt: SRR, 4.01; 95%CI 2.71–4.54). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI 0.42–1.19; P =0.19). Conclusions Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
Objective
Angioimmunoblastic T‐cell lymphoma (AITL) is frequently associated with autoimmune cytopenia (AIC). Whether such patients have a particular phenotype and require particular management is ...unclear.
Method
Angioimmunoblastic T‐cell lymphoma patients from the multicentric database of the Lymphoma Study Association presenting with AIC during disease course were included and matched to AITL patients without AIC (1/5 ratio).
Results
At diagnosis, AIC patients (n = 28) had more spleen and bone marrow involvement (54% vs 19% and 71% vs 34%, P < 0.001), Epstein‐Barr virus replication (89% vs 39%, P < 0.001), gamma globulin titers (median 23 vs 15 g/L, P = 0.002), and proliferating B cells and plasmablasts in biopsies, as compared to control patients (n = 136). The 28 AIC patients had 41 episodes of AIC, diagnosed concomitantly with AITL in 23 (82%) cases. After a median follow‐up of 24 months (range 3‐155), 10 patients relapsed, all associated with AITL relapse.
Conclusion
Our results provide new insight into AIC associated with AITL by highlighting the significant interplay between AITL and B‐cell activation leading to subsequent autoimmunity.
Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma associated with chemoresistance and a poor prognosis. Various nonsynonymous mutations in the R172 residue of IDH2 are present ...in 20% to 30% of AITL patients. In addition to their diagnostic value, these mutations are potentially targetable, especially by isocitrate dehydrogenase (IDH) 2 inhibitor, and therefore their identification in a routine setting is clinically relevant. However, in AITL, the neoplastic cells may be scarce, making the identification of molecular anomalies difficult. We evaluated the diagnostic value of different methods to detect IDH2 mutations in formalin-fixed, paraffin-embedded tumor samples. Immunohistochemistry with an anti-IDH2 R172K antibody, Sanger sequencing, high-resolution melting PCR, allele-specific real-time quantitative PCR, and next-generation sequencing (NGS) were applied to biopsy specimens from 42 AITL patients. We demonstrate that the IDH2 R172K antibody is specific to this amino acid substitution and highly sensitive for the detection of the IDH2R172K variant, the most frequent substitution in this disease. In our study, NGS and allele-specific real-time quantitative PCR displayed a good sensitivity, detecting 96% and 92% of IDH2 mutations, respectively, in contrast to Sanger sequencing and high-resolution melting PCR, which showed a significantly lower detection rate (58% and 42%, respectively). These results suggest that a combination of immunohistochemistry and AS-PCR or NGS should be considered for the identification of IDH2 mutations in AITL in a routine setting.
Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease characterized by recurrent genetic alterations. Several adverse prognostic factors are well known as ...International Prognostic Index (IPI) parameters or MYC and BCL2 and/or BCL6 gene rearrangements (High-Grade B-cell Lymphoma double/triple hit, HGBL-DH/TH, according to the 2016 WHO classification). Other factors are controversial as previous history of indolent lymphoma, cell of origin (COO), co-expression of MYC and BCL2 proteins (double expressor (DE) status), MYC partner gene if rearranged. The aim of this study is to describe a « real life » cohort of patients treated in our institution for aggressive (non-Burkitt) B-cell lymphoma and to evaluate the prognostic impact of phenotypic and genetic alterations.
Methods: We collected clinical and histological characteristics of patients uniformly treated between January 2009 and June 2017 with rituximab R-CHOP/CHOP-like chemotherapy. Treatment was reinforced with high dose methotrexate in case of central nervous system (CNS) localization or HGBL subtype. All tumor samples were analysed for MYC and BCL2 protein expression by immunohistochemistry. BCL2, BCL6 and MYC break were analysed by Interphase Fluorescence In Situ Hybridization (FISH) with breakapart probes. When MYC was rearranged MYC partner gene was analysed with double fusion probes (MYC/IgH, MYC/IgL, MYC/IgK). Positron Emission Tomography (PET scanner) was performed with maximal Standardized Uptake Value (SUV max) at baseline in all patients except 7.
Results: 242 patients were studied. Baseline characteristics were: median age: 61 y (18-88), IPI 3-5: 49.6%, CNS localization: 6.6%. With a median follow-up of 4.4 years, 5y-overall survival (OS) and 5y-progression free survival (PFS) were 72% (66.0-78.5) and 65% (58.5-71.3), respectively. SUV max at baseline was 17,1 (minimum value 2,4 - maximal value 39,3).Histological diagnoses were DLBCL-not otherwise specified (NOS): 57%, transformed DLBCL: 26%, HGBL: 7.9%, primary mediastinal B-cell lymphoma (PMBL): 4.1% and others: 5%. Using Hans algorithm, 48.8% were classified as germinal center (GC), 47.9% as non-GC, 3.3% could not be evaluated and 38% were DE. MYC rearrangement was detected in 36 cases (14.9%) with an immunoglobulin partner gene (IgH, IgL or IgK) in 24 (77.4%) of 31 evaluable cases. BCL2 and BCL6 rearrangement were observed in 45 cases (18.6%) and 62 (25.6%) cases respectively. Fifteen cases were HGBL DH/TH including 7 DH MYC/BCL2, 5 DH MYC/BCL6 and 3 TH MYC/BCL2/BCL6. Four cases were HGBL-NOS. IPI score 3-5 (p<0.0001) and HGBL (p=0.03) were significantly associated with inferior OS. IPI score 3-5 (p<0.0001), DE status (p=0.03), MYC-R (p=0.05) and BCL2-R (p=0.0014) were significantly associated with inferior PFS. Previous indolent lymphoma, COO and MYC partner gene had no impact on OS or PFS.
Conclusions: This monocentric study in a large cohort of aggressive B-cell lymphoma patients treated in real life conditions confirms previous reports on the negative prognostic impact of DE status, MYC and BCL2 translocations and HGBL subtype. These genetic and immuno-histological characteristics should have implications in the design and interpretation of future clinical trials.
Le Bras:Takeda: Research Funding; Pfizer: Other: Travel grant; Jansen: Other: Travel grant. Belhadj:Celgene: Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work. Haioun:servier: Honoraria; amgen: Honoraria; janssen cilag: Consultancy; takeda: Consultancy; gilead: Consultancy; novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy.
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