scholarly journals Pembrolizumab and its role in relapsed/refractory classical Hodgkin’s lymphoma: evidence to date and clinical utility

2018 ◽  
Vol 9 (4) ◽  
pp. 89-105 ◽  
Author(s):  
Polina Shindiapina ◽  
Lapo Alinari
Keyword(s):  
Monoclonal Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Immune Cell ◽  
Single Agent ◽  
Hematologic Malignancies ◽  
Malignant Cell ◽  
Hodgkin's Lymphoma ◽  
Molecular Signaling ◽  
Chl A ◽  
Combination Strategies

Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin’s lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy. The anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have shown similarly remarkable activity in relapsed/refractory cHL and have been approved by the Food and Drug Administration for treatment of this disease. In this article we review the rationale of targeting the PD-1/PD-L1 axis in cHL and the pharmacology of pembrolizumab, and summarize the data on activity and safety profile of this agent in the treatment of relapsed/refractory cHL. We also discuss the potential benefits and pitfalls of using PD-1 blockade in the setting of allogeneic stem-cell transplantation, and summarize ongoing prospective trials of single-agent pembrolizumab and combination strategies as well as future directions.

scholarly journals Radioimmunotherapy in Non-Hodgkin’s Lymphoma: Retrospective Adverse Event Profiling of Zevalin and Bexxar

2019 ◽  
Vol 12 (4) ◽  
pp. 141 ◽  
Author(s):  
Sachpekidis ◽  
Jackson ◽  
Soldatos
Keyword(s):  
Adverse Event ◽  
Monoclonal Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Adverse Event Reporting System ◽  
Hodgkin's Lymphoma ◽  
World Health ◽  
Antibody Treatment ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

The development of monoclonal antibodies has dramatically changed the outcome of patients with non-Hodgkin’s lymphoma (NHL), the most common hematological malignancy. However, despite the satisfying results of monoclonal antibody treatment, only few NHL patients are permanently cured with single-agent therapies. In this context, radioimmunotherapy, the administration of radionuclides conjugated to monoclonal antibodies, is aimed to augment the single-agent efficacy of immunotherapy in order to deliver targeted radiation to tumors, particularly CD20+ B-cell lymphomas. Based on evidence from several trials in NHL, the radiolabeled antibodies 90Y-ibritumomab tiuxetan (Zevalin, Spectrum Pharmaceuticals) and 131I-tositumomab (Bexxar, GlaxoSmithKline) received FDA approval in 2002 and 2003, respectively. However, none of the two radioimmunotherapeutic agents has been broadly applied in clinical practice. The main reason for the under-utilization of radioimmunotherapy includes economic and logistic considerations. However, concerns about potential side effects have also been raised. Driven by these developments, we performed retrospective analysis of adverse events reporting Zevalin or Bexxar, extracted from the FDA’s Adverse Event Reporting System (FAERS) and the World Health Organization’s VigiBase repository. Our results indicate that the two radioimmunotherapeutic agents have both related and distinct side effect profiles and confirm their known toxicological considerations. Our work also suggests that computational analysis of real-world post-marketing data can provide informative clinical insights. While more prospective studies are necessary to fully characterize the efficacy and safety of radioimmunotherapy, we expect that it has not yet reached its full therapeutic potential in modern hematological oncology.

scholarly journals New monoclonal antibodies for non-Hodgkin's lymphoma

2008 ◽  
Vol 19 ◽  
pp. iv60-iv62 ◽  
Author(s):  
J.P. Leonard ◽  
P. Martin ◽  
J. Ruan ◽  
R. Elstrom ◽  
J. Barrientos ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

scholarly journals Recurrent and Hodgkin’s lymphoma-associated multicentric Castleman’s disease in head and neck region

2020 ◽  
Vol 6 (10) ◽  
pp. 1882
Author(s):  
Vinodh Kumar Selvaraj ◽  
Deleep Kumar Gudipudi
Keyword(s):  
Monoclonal Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Treatment Options ◽  
Castleman’S Disease ◽  
Neck Region ◽  
Hodgkin's Lymphoma ◽  
Castleman's Disease ◽  
First Case ◽  
Field Radiation ◽  
Involved Field

<p class="abstract"><strong><span lang="EN-US">Background: </span></strong><span lang="EN-US">Castleman’s disease (CD) is a rare lymphoproliferative disorder. It can involve single (unicentric CD) or multiple (multicentric CD) lymph nodal regions. It occurs predominantly in mediastinum, and treatment options include surgery, radiotherapy, chemotherapy, and monoclonal antibodies. </span></p><p class="abstract"><strong><span lang="EN-US">Methods:</span></strong><span lang="EN-US"> Here, we describe two cases of CD which presented with stridor. The first case was a 38-year-old male, a recurrent multicentric CD in retropharyngeal and cervical lymph nodal regions, treated with radiotherapy and rituximab. The second case was a 25-year-old male, a multicentric CD in lower cervical lymph nodal region, treated with steroids and radiotherapy. He subsequently developed Hodgkin’s lymphoma and was treated for the same with chemotherapy and involved-field radiation therapy (IFRT).</span></p><p class="abstract"><strong><span lang="EN-US">Results: </span></strong><span lang="EN-US">Post-treatment, both the patients were asymptomatic and progression-free at 15 months and 42 months follow-up, respectively.</span></p><p class="abstract"><strong><span lang="EN-US">Conclusions: </span></strong><span lang="EN-US">Combined modality of treatment with radiotherapy and chemotherapy or monoclonal antibodies offers good local control in multicentric CD.</span></p>

scholarly journals The Immune Response to Tumors as a Tool toward Immunotherapy

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
F. Pandolfi ◽  
R. Cianci ◽  
D. Pagliari ◽  
F. Casciano ◽  
C. Bagalà ◽  
...  
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Cancer Colorectal ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Hematologic Malignancies ◽  
The Novel ◽  
Infiltrating Lymphocytes

Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes.

Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines

2005 ◽  
Vol 23 (26) ◽  
pp. 6421-6428 ◽  
Author(s):  
David G. Maloney
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Patient Specific ◽  
Chimeric Antibody ◽  
Target Antigen ◽  
Host Immune System ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.

scholarly journals MP7: FAMILIES WITH BOTH NON-HODGKIN'S LYMPHOMA (NHL) AND MYELOMA (MM): ANTICIPATION AND MALE TRANSMISSION

2016 ◽  
Vol 64 (3) ◽  
pp. 807.1-807
Author(s):  
PH Wiernik ◽  
JP Dutcher
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Hematologic Malignancies ◽  
Hodgkin's Lymphoma ◽  
Same Sex ◽  
Autosomal Region ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Affected Sib Pairs ◽  
The Relationship ◽  
Sib Pairs

Purpose of StudyTo determine whether genetic rather than environmental factors may be responsible for the occurrence of these neoplasms in families.Methods UsedWe interrogated our registry of >700 pedigrees of families (fams) with multiple hematologic malignancies. We identified 31 fams with both NHL and MM in their pedigrees. In 16 pedigrees a parent and child were affected (12 father-child pairs and 4 mother-child pairs). Fifteen affected sib pairs were identified in the 31 fams, 10 same sex pairs and 5 male-female pairs. Six of the 31 pedigrees had only 1 affected pair. More distant relationships were observed in other fams.Summary of ResultsMale transmission was evident in 25 fams and female transmission was observed in 6. NHL and MM cases had at least 1 unaffected generation (gen) between them in 8 pedigrees, and the diseases occurrred in sequential (13 fams) or the same gen in 10 fams. MM was the diagnosis (dx) in the youngest affected gen in 9 pedigrees, NHL in 13 pedigrees and both occurred in the youngest gen in 9 fams. The median age at dx of 29 NHL patients for whom data were available was 55 yrs (range, 20–99 yrs), and the median age at dx of 26 MM cases was 56 yrs (range, 30–82 yrs). Ten of 26 MM patients were <50 years old at dx. The presence or absence of anticipation could be assessed in 15 of the 31 pedigrees. All 15 displayed anticipation in terms of succeeding gens developing NHL or MM at an earlier age than did the previous gens (median −19 yrs, range −6 to −56 yrs).ConclusionsWe demonstrate anticipation in 15 assessible fams with both NHL and MM, a feature of familial MM that we previoiusly reported (Despande HA, et al: Br J Haematol 1998). More advanced, aggressive disease at dx in the youngest gen is another feature of anticipation, and was observed in 9 of 13 fams in which it could be assessed. Demonstration of anticipation in all 15 evaluable fams suggests a genetic basis for the relationship between these two B-cell disorders. The increase of same sex sib pairs among affected sib pairs implicates a locus on a pseudo-autosomal region of the X chromonsome as potentially responsible for this observation, as we have previously reported for Hodgkin's lymphoma (Horwitz M, Wiernik PH, Am J Hum Genet 1999). Myeloma and non-Hodgkin's lymphoma may have common genetic causation; molecular studies of these fams are planned.

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