Nonlinear pharmacokinetics of rituximab in non-Hodgkin lymphomas: A pilot study.

AIMS: Rituximab is an anti-CD20 monoclonal antibody approved in non-Hodgkin lymphoma (NHL). This study aimed to assess the relationship between antigen mass and nonlinear pharmacokinetics of rituximab in NHL patients. METHODS: In a retrospective cohort of 25 NHL patients treated with rituximab, antigen mass was assessed at baseline by measuring metabolic tumour volume (MTV) by positron emission tomography. Rituximab pharmacokinetics was described using a semimechanistic 2-compartment model including a latent target antigen. Rituximab target-mediated elimination was described as irreversible binding between rituximab and it target. Histology (follicular or diffuse large B-cell lymphomas), initial MTV and body weight were tested as covariates on pharmacokinetic parameters. RESULTS: The model allowed a satisfactory description of rituximab serum concentrations. Target-mediated elimination was maximum at the beginning of treatment and became negligible towards the end of follow-up. The second-order elimination of rituximab due to target binding and complex elimination increased with baseline MTV. Central volume of distribution increased with body weight (P = .022) and baseline MTV (P = .005). CONCLUSIONS: This study quantified for the first time the target-mediated elimination of rituximab in NHL patients and confirmed rituximab retention by antigen mass.

Post-treatment positron emission tomography-computed tomography is highly predictive of outcome in Plasmablastic lymphoma.

PURPOSE: Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B cell lymphomas (DLBCL) clinically characterized by a poorer prognostic. Few clinical and imaging data are available and derived from pooled case reports and small series. The aim of the study was to evaluate the FDG avidity at baseline and the utility of 18-Fluorodeoxyglucose (FDG) positron-emission-tomography/computed-tomography (PET/CT) for staging and response assessment. METHODS: Patients with newly diagnosed PBL seen at Lymphoma Study Association centers during the period 2005-2015 were included if they underwent a PET/CT at staging and at the end of treatment (eotPET) and had received an anthracycline-based first line therapy. EotPET scans were analyzed using the 5-point-scale visual analysis in accordance with Lugano criteria. Patients were classified in complete metabolic response (CMR) or no-CMR including partial metabolic response (PMR), stable disease (SD) and progression disease (PD). EotPET results were assessed for the ability to predict event free survival (EFS) and overall survival (OS). RESULTS: Thirty-five PBL patients fulfilled the inclusion criteria. The median follow-up was 34 months (2.8-120 months). FDG avidity was found in all patients at diagnosis. Most patients (80%) achieved CMR, and 20% were no-CMR including 9% PMR, 6% SD, and 6% PD. A CMR after first line chemotherapy predicted higher EFS (p < 0.0001) and OS (p = 0.0006). CONCLUSIONS: This study confirmed the FDG avidity of PBL subtype and the usefulness of PET/CT scanning in restaging an aggressive lymphoma at the completion of chemotherapy. EotPET can predict outcomes following treatment in patients with PBL.

Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program.

Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible.

Prevalence and diagnostic performance of iron deficiency in polycythemia.

INTRODUCTION: Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency and to evaluate the diagnostic performance of serum ferritin in polycythemia vera. PATIENTS AND METHOD: This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis. RESULTS: Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR = 115; 95% CI [14.4-918.2], p < 0.0001) and the sensitivity and specificity of serum ferritin were 52.63% and 100% respectively. CONCLUSION: Assessment of iron deficiency should be part of the initial evaluation of polycythemia. Iron deficiency had a high specificity during polycythemia vera.

Listeria endocarditis and spondylodiscitis: A case report and review of the literature.

A 75-year-old man with an aortic bioprosthesis was admitted with polyarthritis in a non-febrile setting. Blood cultures were positive for Listeria monocytogenes. The diagnosis of Listeria endocarditis and spondylodiscitis was evoked. These are two unusual forms of listeriosis. The evolution was favorable after antibiotic therapy.

Long-term follow-up of tandem high-dose therapy with autologous stem cell support for adults with high-risk age-adjusted international prognostic index aggressive non-Hodgkin Lymphomas: a GOELAMS pilot study.

Single high-dose therapy (HDT) followed by autologous peripheral blood stem cell (PBSC) support improves complete response and overall survival (OS) in untreated aggressive non-Hodgkin's lymphoma (NHL). However, patients with a high age-adjusted international prognostic index (aa-IPI equal to 3) still have poor clinical outcome despite high dose intensity regimen. To improve complete response in this subgroup, the French Groupe Ouest-Est des Leucémies et Autres Maladies du Sang (GOELAMS) conducted a pilot phase II trial (073) evaluating tandem HDT with PBSC support in a series of 45 patients with aa-IPI equal to 3 untreated aggressive non-Hodgkin's lymphoma. After induction with an anthracyclin-containing regimen, responders underwent tandem HDT conditioned by high-dose mitoxantrone plus cytarabine for the first HDT and total-body irradiation (TBI), carmustine, etoposide, and cyclophosphamide for the second HDT. Thirty-one patients out of 41 evaluable patients completed the program. There were 4 toxic deaths. The complete response rate was 49%. With a median follow-up of 114 months for surviving patients, the OS was 51%, and 19 out of the 22 patients (86%) who reached a complete response are alive and relapse-free. Recent prospective evaluation of quality of life and comorbidities of surviving patients does not reveal long-term toxicities of the procedure. In the era of monoclonal antibodies and response-adapted therapy, the role of tandem HDT still need to be determined.

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

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.

Discovery of a gamma heavy chain disease in a patient followed-up for a lymphoplasma cell proliferative disorder.

Gamma-heavy chains disease is a rare disease, with very few cases described in the literature. It is characterized by the presence of a monoclonal gamma-heavy chain without associated light chain. Its prevalence and prognosis are unknown. We report here the accidental discovery of a case of gamma-heavy chain disease during a pancytopenia exploration, performed in the hospital, in a patient known since 2002 for a lymphoplasmacytic type lymphoma first localized in bone marrow.

Pulmonary toxoplasmosis in immunocompromised patients with interstitial pneumonia: a single-centre prospective study assessing PCR-based diagnosis.

AIMS: Pulmonary toxoplasmosis has become a very rare parasitic infection since the advent of highly active antiretroviral therapies. It is generally diagnosed by the direct microscopic observation of Toxoplasma gondii tachyzoites in bronchoalveolar lavage fluid (BALF). The aim of this study was to assess possible improvements in diagnostic performance associated with the use of real-time PCR. METHODS: This prospective study was carried out on BALFs obtained from immunocompromised patients over a 2-year period. We systematically compared the results of conventional staining with those of molecular detection. RESULTS: Two cases of pulmonary toxoplasmosis were diagnosed for a total of 336 samples. PCR did not detect any additional cases and was more time-consuming than conventional staining. CONCLUSIONS: Conventional staining is a reliable technique and is probably the most appropriate method for experienced microbiology laboratories, whereas T. gondii-specific PCR may be useful for laboratories with less experience in parasitology. TRIAL REGISTRATION NUMBER: 2015_030, May 27th 2015.

A CASE OF CHORIORETINOPATHY AS FIRST MANIFESTATION OF HODGKIN'S LYMPHOMA.

PURPOSE: To report a case of chorioretinopathy, which preceded diagnosis of Hodgkin's lymphoma. METHODS: Single patient case report. RESULTS: A 61-year-old woman with a history of breast cancer in remission and low-grade follicular lymphoma without criteria of high tumor burden presented with bilateral multifocal chorioretinopathy. The usual etiologies of chorioretinopathy were excluded, and subsequent onset of fever and back pain revealed the diagnosis of Hodgkin's lymphoma. The evolution of this case of ocular involvement was concordant with that of Hodgkin's lymphoma. CONCLUSION: The authors describe a case of Hodgkin's lymphoma postdating the onset of chorioretinopathy, emphasizing the need to research an underlying disorder when faced with any inflammatory intraocular disease, and the role of indocyanine green angiography in the diagnosis and follow-up of posterior uveitis.

Frequent engagement of RelB activation is critical for cell survival in multiple myeloma.

The NF-κB family of transcription factors has emerged as a key player in the pathogenesis of multiple myeloma (MM). NF-κB is activated by at least two major signaling pathways. The classical pathway results in the activation of mainly RelA containing dimers, whereas the alternative pathway leads to the activation of RelB/p52 and RelB/p50 heterodimers. Activating mutations in regulators of the alternative pathway have been identified in 17% of MM patients. However, the status of RelB activation per se and its role in the regulation of cell survival in MM has not been investigated. Here, we reveal that 40% of newly diagnosed MM patients have a constitutive RelB DNA-binding activity in CD138(+) tumor cells, and we show an association with increased expression of a subset of anti-apoptotic NF-κB target genes, such as cIAP2. Furthermore, we demonstrate that RelB exerts a crucial anti-apoptotic activity in MM cells. Our findings indicate that RelB activation is key for promoting MM cell survival through the upregulation of anti-apoptotic proteins. Altogether, our study provides the framework for the development of new molecules targeting RelB in the treatment of MM.