scholarly journals Myasthenia gravis, myositis, myocarditis and anti-titin antibodies after Nivolumab/Ipilimumab: response with plasmapheresis

2021 ◽  
Author(s):  
Maria Eduarda Slhessarenko Fraife Barreto ◽  
Arthur Malzyner ◽  
Nelson Hamerschlak ◽  
Maurício Muradian ◽  
Alessandra Delavance ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Cardiac Involvement ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Complete Recovery ◽  
Large B Cell Lymphoma ◽  
Autoimmune Myositis ◽  
First Choice ◽  
Titin Antibodies ◽  
Sixth Nerve

Context: Severe neurological manifestations following use of immune checkpoint inhibitors (ICIs) occur in 0.93% of patients, and together with cardiac toxicity have the higher lethality. Myasthenia gravis (MG) and polymyositis (PM) are rare, and treatment includes discontinuation of the immunotherapy, corticosteroids, and intravenous immunoglobulin (IVIG), with occasional use of plasmapheresis (PLEX). Biomarkers are not consistently reported. We report the case of a patient with MG, PM and myocarditis after ICI, with positive anti-titin antibodies and response to plasmapheresis. Case report: 81-year-old male developed ascending, subacute, progressive tetraparesis, dysphagia, ophthalmoparesis, and respiratory failure 2 weeks after second cycle of nivolumab/ipilimumab for metastatic melanoma. Physical examination showed: globally reduced strength, hypoactive reflexes, bilateral sixth nerve palsy and bilateral semi-ptosis. Prostigmine test was positive and electroneuromyography was compatible with myopathy. Labs revealed CPK 4000 U/L, troponin 9000U/L, autoimmune myositis panel negative, anti-titin antibodies (described in paraneoplastic MG and associated with severity) positive and cardiac MRI without fibrosis. Clinical picture was compatible with MG and PM with cardiac involvement. He received methylprednisolone and six PLEX sessions, with complete recovery. Four months after treatment, he developed cognitive impairment and large B-cell lymphoma (ICI complication). Conclusions: PM and MG may occur after ICI, especially in the first cycles, and anti-titin may be a biomarker of severity in these patients. Although guidelines recommend adding IVIG or PLEX in refractory or severe cases, PLEX may be first choice, especially if multiple ICI are present.

scholarly journals New agents and regimens for diffuse large B cell lymphoma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Liang Wang ◽  
Lin-rong Li ◽  
Ken H. Young
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Classification Systems ◽  
Genetic Classification ◽  
Standard Regimen ◽  
Treatment Approaches ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractAs a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma (DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, monoclonal antibodies, antibody–drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic classification systems are introduced to guide individualized treatment for DLBCL.

Treatment with doxorubicin-based protocol in cardiac involvement diffuse large B-cell lymphoma: A case report

2021 ◽  
pp. 107815522110351
Author(s):  
Atakan Tekinalp ◽  
Taha U Kars ◽  
Hatice Z Dikici ◽  
Pınar D Yılmaz ◽  
Sinan Demircioğlu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
B Cell ◽  
Cardiac Involvement ◽  
Cell Lymphoma ◽  
Vena Cava ◽  
Standardized Uptake Value ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Introduction Cardiac involvement in diffuse large B-cell lymphoma is a rare entity in non-Hodgkin lymphomas. Symptoms are usually related to heart failure. Patients who are severely symptomatic due to cardiac mass could be considered treatment as soon as possible. In this report, we present a patient diagnosed with diffuse large B-cell lymphoma with cardiac involvement. Case Report A 61-year-old female patient was admitted to our unit with gastric biopsy diffuse large B-cell lymphoma. Computerized tomography of the chest and positron emission tomography/computed tomography demonstrated a neoplastic mass in the intra-atrial septum extended to inferior vena cava (5 × 4 cm in size and standardized uptake value maximum 24.6). She was in stage III and in the high-risk group. Because of pronounced heart failure findings associated with the mass-specific chemotherapy was planned early. Management & Outcome Although a fraction of ejection was 60% by echocardiography before the treatment, she had a cardiac risk for doxorubicin due to being over 60 years old and hypertension. Complete remission was achieved after three cycles of rituximab–cyclophosphamide–doxorubicin–vincristine and methylprednisolone protocol including doxorubicin. Treatment was completed with six cycles and she was followed up for three months. Discussion Because of the cardiotoxicity of doxorubicin-based protocols, patients should be evaluated according to cardiac functions before and during the chemotherapy.

scholarly journals The use of checkpoint inhibitors in children with non-Hodgkin lymphomas

2020 ◽  
Vol 19 (2) ◽  
pp. 112-120
Author(s):  
A. V. Kozlov ◽  
I. V. Kazantsev ◽  
T. V. Yukhta ◽  
P. S. Tolkunova ◽  
A. G. Gevorgyan ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Median Number ◽  
Hematopoietic Stem ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The majority of children with NHL can be cured with first-line therapy but 10–25% of affected patients develop relapsed or refractory disease (R-R). The prognosis in these cases is unfavorable, no matter what form of modern treatment is adopted. New approaches to the treatment of this small, yet important, group of patients need to be introduced, including, first and foremost, targeted therapy and immunotherapy. As is known, PD-L1 is frequently expressed in non-Hodgkin lymphomas (NHL), which means that the use of checkpoint inhibitors (CPI) is theoretically justified. Objectives: to analyze the results of treatment with checkpoint inhibitors Nivolumab and Pembrolizumab in children with R-R NHL. The study was approved by the Independent Ethics Committee of the I.P. Pavlov First Saint-Petersburg State Medical University. We used CPIs in 8 children with R-R NHL undergoing treatment at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation. The median age was 12 (2–17) years. The distribution of the patients by diagnosis was as follows: primary mediastinal large B-cell lymphoma (PMBCL, n = 3), peripheral T-cell lymphoma (PTCL, n = 2), diffuse large B-cell lymphoma (n = 1), lymphoblastic lymphoma (n = 2). The median number of prior lines of therapy was 3 (1–5), and all patients had received at least 1 line of standard treatment. Refractory NHL was observed in 5 cases, and 3 patients had had multiple relapses (≥ 3). All patients had progression of their primary disease at the time of prescription of the CPI therapy. Nivolumab was administered at a dose of either 1 mg/kg (n = 4) or 3 mg/kg (n = 3) every 2 weeks, Pembrolizumab - at a dose of 2 mg/kg once every 3 weeks (n = 1). The median number of CPI doses received by the patients was 5.5 (2–12). In 5 patients, CPIs were administered as monotherapy, in 3 – in combination with cytostatic agents: FLAG, Gemcitabine and intrathecal triples (n = 1), Brentuximab vedotin (n = 1) and Bendamustine (n = 1). The efficacy of the treatment was evaluated in accordance with the LYRIC criteria. Once remission was achieved, we used hematopoietic stem cell transplantation and/or radiotherapy for consolidation. Response to the CPI therapy was observed in 4 out of 8 patients (complete response – in 2 patients). Interestingly, only patients with PMBCL and PTCL responded to the treatment. At the median follow-up of 368 (36–879) days, 5 patients were alive, with three of them remaining in long-term remission. During the follow-up period, there was only 1 clinically significant complication (cytopenia) that resolved after treatment with glucocorticosteroids. Finally, we would like to point out that this paper is one of the first reports on the successful use of CPIs in children with R-R NHL. PMBCL and PTCL turned out to be responsive to the treatment. This therapy can be used to achieve remission or possibly even cure in children whose only option would be palliative care if they were treated with standard approaches.

scholarly journals Ibrutinib Can Induce Complete Remissions and Sustained Responses in Refractory Cutaneous or Leg-Type Diffuse Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4237-4237
Author(s):  
Johannes Bloehdorn ◽  
Stephanie Ellen Weissinger ◽  
Anca Sindrilaru ◽  
Stefan Schoensteiner ◽  
Thorsten Peters ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Individual Treatment ◽  
Large B Cell Lymphoma ◽  
Sustained Responses ◽  
Myd88 L265p ◽  
Large B Cell

Abstract Background: Primary cutaneous diffuse large B-cell lymphoma, leg-type (LT-DLBCL) is an extremely aggressive DLBCL subtype typically occurring at lower extremities and with very poor prognosis due to early relapses and refractory (R/R) disease. Previous studies have shown increased BCR dependence in DLBCL being observed in association with the mutation status of BCR associated genes and MYD88. Aim: Primary goal was to assess the clinical course in patients with primary cutaneous DLBCL and to elucidate the potential of alternative treatments with regard to molecular characteristics. Methods: We identified 16 patients with cutaneous DLBCL treated at our center of which 8 patients had typical localization and were histologically confirmed as LT-DLBCL. The other 8 patients showed cutaneous DLBCL at other anatomic sites (DLBCL-OS) and were classified as DLBCL/DLBCL NOS. Three R/R patients received ibrutinib as off-label individual treatment attempt (420 mg daily). We extended the clinical and molecular analysis for the ibrutinib exposed DLBCL by 1 R/R oropharyngeal DLBCL. Specimen from R/R ibrutinib exposed and 3 other patients were analyzed for CD79B, MYD88, CARD11 and BTK mutations by targeted resequencing analysis. PD-1/PD-L1 expression was assessed in 2 cases with relapse after ibrutinib. Treatment was initiated after signed informed consent. Results: The median age at diagnosis was 51 years in DLBCL-OS and 80 years in LT-DLBCL (total range 37-91). Patients received a median of 2 (0-7) treatments and response to last chemotherapy was different for DLBCL-OS (6 complete remissions (CR), 2 R/R) and LT-DLBCL (2CR, 5R/R). One LT-DLBCL patient showed stable disease (SD) without treatment. LT-DLBCL patients showed a significantly shorter median overall survival (OS) (21,5 months vs. not reached, p=0.009). After ibrutinib treatment we observed 1 ongoing CR for 10 months till date for a DLBCL-OS with CD79B p.Y197S and MYD88 L273P mutation and 1 CR for 6 months in a LT-DLBCL being WT for all sequenced genes. However, this patient relapsed with a highly proliferative disease and died shortly after. The 3rd patient with LT-DLBCL had an isolated MYD88 L265P mutation and showed a PR for 1 month. Samples from patients with indolent clinical course showed a MYD88 p.S251N and BTK p.P385S mutation (LT-DLBCL with SD) or were WT for all sequenced genes (2 patients with DLBCL-OS and ongoing CR). The patient with R/R oropharyngeal DLBCL had a MYD88 L265P and CD79B c.587A mutation, 4 prior treatment regimen and fulminant progression during the last 2 treatments. Initial response to ibrutinib was rapid with a drop of LDH levels from 2200 U/L to 620 U/L within 7 days and consecutive decrease to 323 U/L. However, this patient relapsed after 30 days of treatment. Immunomodulatory effects of ibrutinib and potential synergistic treatment with checkpoint inhibitors have previously been suggested. We specifically investigated PD-1/PD-L1 expression in tissues obtained from the two patients progressing after ibrutinib treatment. Remarkably, we observed increased expression for PD-1 (moderate) and PD-L1 (strong) in non-tumor bystander cells. Treatment with nivolumab was initiated in 1 patient with early clinical benefit. However, the patient refused the continuation of this treatment. Conclusion: Patients with LT-DLBCL are older and show a poor clinical course compared to cutaneous DLBCL at other anatomic sites. MYD88 L265P mutations were observed only in chemo-refractory cases with extranodal DLBCL. Ibrutinib can induce complete remissions and sustained responses in chemo-refractory extranodal DLBCL but relapses may be more aggressive and disseminated. Mutational patterns and ibrutinib response were in line with previous hypothetical models for sensitivity to BCR inhibition. Combining ibrutinib and checkpoint inhibitors may be considered in future trials for LT-DLBCL patients. Disclosures Weissinger: Bristol-Myers Squibb: Research Funding. Viardot:Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

scholarly journals Right upper quadrant pain and mass in a 41-year-old previously healthy man: a presenting feature of HIV-associated extranodal diffuse large B cell lymphoma with cardiac involvement

2012 ◽  
Vol 2012 (apr28 1) ◽  
pp. bcr1120115217-bcr1120115217 ◽  
Author(s):  
A. Vivekanandarajah ◽  
V. R. Bhatt ◽  
B. Krishnarasa ◽  
S. Murukutla ◽  
A. Brenner ◽  
...  
Keyword(s):  
B Cell ◽  
Cardiac Involvement ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Quadrant Pain ◽  
Large B Cell Lymphoma ◽  
Healthy Man ◽  
Large B Cell

scholarly journals Usefulness of transthoracic echocardiogram in management of cardiac involvement in large B-Cell lymphoma: a case report

2015 ◽  
Vol 82 (4) ◽  
Author(s):  
Matteo Ruzzolini ◽  
Gaetano Luca Panetta ◽  
Antonietta Evangelista ◽  
Carlo Peraldo Neja ◽  
Paolo Azzolini
Keyword(s):  
Mediastinal Mass ◽  
Cardiac Involvement ◽  
B Cell Lymphoma ◽  
Primary Lymphoma ◽  
Transthoracic Echocardiogram ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Risk Rate ◽  
The Right ◽  
Prompt Diagnosis

Primary lymphoma often involve the heart, especially the right side. Prompt diagnosis is necessary to start the right therapy and decrease symptoms and death risk rate. Transthoracic echocardiogram is the first line exam to perform when symptoms are suspicious of mediastinal mass.

scholarly journals Cardiac Involvement by HIV-Associated DLBCL

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Charles T. Mupamombe ◽  
Jude Noel ◽  
Derek B. Laskar ◽  
Liza Valdivia
Keyword(s):  
Cardiac Involvement ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Organ System ◽  
Hiv Positive ◽  
People Living With Hiv ◽  
Aggressive Disease ◽  
Large B Cell Lymphoma ◽  
Different Types ◽  
Living With Hiv

Non-Hodgkin’s lymphoma (NHL) is a common AIDS-defining malignancy among people living with HIV. Of the different types of NHLs, diffuse large B-cell lymphoma (DLBCL) is the most common. Prognosis of DLBCL has improved over the years in the general population but remains relatively poor in HIV-positive individuals. Almost any organ system can be affected by DLBCL; however, cardiac involvement remains rare and suggests aggressive disease. We present a case of DLBCL in an HIV-positive patient, who had cardiac involvement, with the only clue to cardiac involvement being symptom being tachycardia and dysphagia.

scholarly journals Sp17 Protein Expression and Major Histocompatibility Class I and II Epitope Presentation in Diffuse Large B Cell Lymphoma Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Kamel Ait-Tahar ◽  
Amanda P. Anderson ◽  
Martin Barnardo ◽  
Graham P. Collins ◽  
Chris S. R. Hatton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mononuclear Cells ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Cytotoxic T Cell ◽  
Peripheral Blood Mononuclear ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Improved therapies are urgently needed for patients with diffuse large B cell lymphoma (DLBCL). Success using immune checkpoint inhibitors and chimeric antigen receptor T cell technology has fuelled demand for validated cancer epitopes. Immunogenic cancer testis antigens (CTAs), with their widespread expression in many tumours but highly restricted normal tissue distribution, represent attractive immunotherapeutic targets that may improve treatment options for DLBCL and other malignancies. Sperm protein 17 (Sp17), a CTA reported to be immunogenic in ovarian cancer and myeloma patients, is expressed in DLBCL. The aim of the present study was to investigate Sp17 epitope presentation via the presence of a cytotoxic T cell (CTL) and a CD4 T-helper (Th) response in DLBCL patients. A significant γ-interferon CTL response was detected in peripheral blood mononuclear cells of 13/31 DLBCL patients following short-term cell stimulation with two novel HLA-A⁎0201 peptides and one previously reported HLA-A⁎0101-restricted nine-mer Sp17 peptide. No significant responses were detected in the HLA-A⁎0201-negative DLBCL patients or four healthy subjects. A novel immunogenic 20-mer CD4 Th Sp17 peptide was detected in 8/17 DLBCL patients. This is the first report of a CTL and a CD4 Th response to Sp17 in DLBCL and supports Sp17 as a potential immunotherapeutic target for DLBCL.

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