scholarly journals Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Razan Mohty ◽  
Rémy Dulery ◽  
Abdul Hamid Bazarbachi ◽  
Malvi Savani ◽  
Rama Al Hamed ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Complete Response ◽  
Current Treatment ◽  
Novel Therapies ◽  
Classical Hodgkin Lymphoma ◽  
Hematopoietic Stem ◽  
Drug Conjugates ◽  
Check Point Inhibitors ◽  
Frontline Therapy

AbstractHodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody–drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.

scholarly journals Therapeutic Advances in Oncology

2021 ◽  
Vol 22 (4) ◽  
pp. 2008
Author(s):  
Jinsha Liu ◽  
Priyanka Pandya ◽  
Sepideh Afshar
Keyword(s):  
Small Molecules ◽  
New Technologies ◽  
Treatment Options ◽  
Current Treatment ◽  
Bispecific Antibodies ◽  
Gene Therapies ◽  
Therapeutic Modalities ◽  
The Past ◽  
Drug Conjugates ◽  
Novel Targets

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.

scholarly journals Allo-HSCT in transplant-naïve patients with Hodgkin lymphoma: a single-arm, multicenter study

2019 ◽  
Vol 3 (24) ◽  
pp. 4264-4270 ◽  
Author(s):  
Emma Das-Gupta ◽  
Kirsty J. Thomson ◽  
Adrian J. C. Bloor ◽  
Andrew D. Clark ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Complete Response ◽  
Primary Objective ◽  
Mixed Chimerism ◽  
Hematopoietic Stem ◽  
Positron Emission ◽  
Computed Tomography Scanning ◽  
Unrelated Donors

Abstract We evaluated the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in transplant-naïve patients with relapsed/refractory Hodgkin lymphoma (HL) who failed to attain metabolic complete response (mCR) to 1 to 2 lines of salvage chemotherapyThose with residual but nonprogressive disease assessed by positron emission tomography/computed tomography scanning were eligible. An additional 1 to 2 cycles of salvage therapy were permissible in those with progressive disease or when required to bridge to allo-HSCT, with additional imaging at baseline before transplantation. Conditioning consisted of carmustine, etoposide, cytarabine, melphalan, and alemtuzumab. Donor lymphocyte infusions (DLI) were administered for mixed chimerism or residual or relapsed disease. Eleven patients had sibling donors, 13 had HLA-matched unrelated donors, and 7 had HLA-mismatched unrelated donors. There were no graft failures, and no episodes of grade 4 acute graft-versus-host disease (GVHD); only 19.4% of patients had grade 2 to 3 GVHD, and 22.2% had extensive chronic GVHD. The non-relapse mortality rate was 16.1% (95% confidence interval [CI], 7.1%-34.5%). Relapse incidence was 18.7% (95% CI, 8.2%-39.2%). The study met its primary objective, with a 3-year progression-free survival of 67.7% (95% CI, 48.4%-81.2%). Survival outcomes were equivalent in those with residual metabolically active disease immediately before transplantation (n = 24 [70.8%; 95% CI, 17.2%-83.7%]). Two of the 5 patients who relapsed received DLI and remained in mCR at latest follow-up, with a 3-year overall survival of 80.7% (95% CI, 61.9%-90.8%). We demonstrate encouraging results that establish a potential role for allo-HSCT in selected high-risk patients with HL. This trial was registered at www.clinicaltrials.gov as #NCT00908180.

Novel Agents in the Therapy of Hodgkin Lymphoma

2015 ◽  
pp. e479-e482 ◽  
Author(s):  
Stephen Ansell
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoints ◽  
Novel Therapies ◽  
Cellular Composition ◽  
Standard Chemotherapy ◽  
Favorable Prognosis ◽  
Drug Conjugates ◽  
B Cell Malignancy ◽  
Antibody Drug ◽  
Cell Malignancy

Hodgkin lymphoma (HL) is a B-cell malignancy that typically has a favorable prognosis when treated with chemotherapy, often in combination with radiation therapy. The prognosis for patients whose disease relapses or is refractory, however, is far less favorable and novel therapies are needed for these patients. The unique cellular composition of HL provides a number of opportunities to target either the malignant Reed-Sternberg cell or the inflammatory tumor microenvironment. Antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints, have all demonstrated activity in HL. Current and future trials are exploring the use of these agents in combination with each other and with standard chemotherapy.

scholarly journals Metachromatic Leukodystrophy: Diagnosis and Treatment Challenges

Bionatura ◽  
2021 ◽  
Vol 3 (3) ◽  
pp. 2083-2090
Author(s):  
Nayibe Tatiana Sanchez-Alvarez ◽  
Paula Katherine Bautista-Niño ◽  
Juanita Trejos-Suárez ◽  
Norma Cecilia Serrano-Diaz
Keyword(s):  
Intracellular Signaling ◽  
Metachromatic Leukodystrophy ◽  
Treatment Options ◽  
Current Treatment ◽  
Significant Advance ◽  
Rapid Progression ◽  
Hematopoietic Stem ◽  
Enzyme Replacement ◽  
Bibliographic Search ◽  
Systemic Symptoms

Metachromatic leukodystrophy is a neurological disease of the lysosomal deposit that has a significant impact given the implications for the neurodegenerative deterioration of the patient. Currently, there is no treatment available that reverses the development of characteristic neurological and systemic symptoms. Objective. Carry out an updated bibliographic search on the most critical advances in the treatment and diagnosis for LDM. A retrospective topic review published in English and Spanish in the Orphanet and Pubmed databases. Current treatment options, such as enzyme replacement therapy and hematopoietic stem cell transplantation aimed at decreasing the rapid progression of the disease, improving patient survival; however, these are costly. The pathophysiological events of intracellular signaling related to the deficiency of the enzyme Arylsulfatase A and subsequent accumulation of sulphatides and glycosylated ceramides have not yet been established. Recently, the accumulation of C16 sulphatides has been shown to inhibit glycolysis and insulin secretion in pancreatic cells. The significant advance in technology has allowed timely diagnosis in patients suffering from LDM; however, they still do not have an effective treatment.

scholarly journals Anti-Angiogenic Agent Combined with Anti-PD-1 Immunotherapy Showed Activity in Patients With Classical Hodgkin Lymphoma Who Have Failed Immunotherapy: A Retrospective Case Report Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Yan ◽  
Jialin Ma ◽  
Shuna Yao ◽  
Zhihua Yao ◽  
Haiying Wang ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin Lymphoma ◽  
Low Dose ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Study Patient ◽  
Solid Cancer ◽  
Classical Hodgkin Lymphoma ◽  
Retrospective Case

BackgroundPD-1/PD-L1 inhibitor immunotherapy has showed impressive activity in various cancers, especially relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). However, acquired resistance is inevitable for most patients. Sometimes severe side effects also lead to treatment termination. When immunotherapy failed, alternative treatment options are limited. In the past few years, we have used the anti-angiogenic agent apatinib and PD-1 inhibitor camrelizumab to treat cHL patients who failed prior immunotherapy. In this study, we analyzed the data of these patients.Patients and MethodsPatients with r/r cHL who had failed immunotherapy and subsequently received apatinib-camrelizumab (AC) combination therapy were included in this study. Patient data were collected from medical records and follow-up system. The efficacy and safety of AC therapy were analyzed.ResultsSeven patients who failed immunotherapy were identified in our database, of which five patients acquired immunotherapy resistance and two patients experienced severe side effects. They received a combination of camrelizumab (200 mg every four weeks) and apatinib (425 mg or 250 mg per day). As of the cut-off date, these patients had received a median of 4 cycles (range, 2 - 31) of treatment. Two (2/7) patients achieved complete response, four (4/7) partial response, and one (1/7) stable disease. The median progression-free survival was 10.0 months (range, 2.0 – 27.8). Low-dose apatinib (250 mg) plus camrelizumab was well tolerated and had no unexpected side effects. Besides, no reactive cutaneous capillary endothelial proliferation was observed in AC-treated patients.ConclusionsLow dose apatinib plus camrelizumab might be a promising treatment option for r/r cHL patients who have failed immunotherapy. This combination treatment is worthy of further investigation in more patients including solid cancer patients who have failed immunotherapy.

scholarly journals Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients

Blood ◽  
2018 ◽  
Vol 131 (15) ◽  
pp. 1698-1703 ◽  
Author(s):  
Neha Mehta-Shah ◽  
Nancy L. Bartlett
Keyword(s):  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Classical Hodgkin Lymphoma ◽  
Antibody Drug Conjugate ◽  
Barr Virus ◽  
Drug Conjugates ◽  
Improved Outcomes ◽  
Individualized Approach ◽  
Epstein Barr ◽  
Antibody Drug

AbstractAddition of brentuximab vedotin, a CD30-targeted antibody–drug conjugate, and the programmed death 1 (PD-1) inhibitors nivolumab and pembrolizumab to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine may result in prolonged survival with a minimal or modest effect on quality of life. Participation in clinical trials evaluating new approaches such as combination immune checkpoint inhibition, novel antibody–drug conjugates, or cellular therapies such as Epstein-Barr virus–directed cytotoxic T lymphocytes and chimeric antigen receptor T cells offer additional options for eligible patients.

scholarly journals Very High Efficacy of Bendamustine, Gemcytabine and Dexamethasone (BGD) in Relapsed/Refractory Classical Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5366-5366
Author(s):  
Ryszard Swoboda ◽  
Jacek Najda ◽  
Katarzyna Dulik ◽  
Anna Kwiatkowska-Pamula ◽  
Maja Twardosz ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Initial Response ◽  
Median Number ◽  
Primary Study ◽  
Upper Respiratory Tract ◽  
Salvage Regimen ◽  
Skin Reactions ◽  
Hematopoietic Stem

Abstract Introduction. Although Hodgkin lymphoma (HL) is one of the most curable malignancies, 10-30% of patients experience resistance or relapse following initial response. Treatment options for relapsed/refractory (R/R) disease include usually multi-agent chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT). Although many chemotherapy-based regimens are used as salvage, the optimal one has not been defined so far. The goal of this study was to evaluate efficacy and safety of bendamustine in combination with gemcitabine and dexamethasone (BGD) in R/R HL. Patients and Methods. This was a retrospective, single center study, including 30 consecutive R/R HL patients treated between 2016 and 2018. Median age was 33 (19-82) years. Ten patients (33%) had been pre-treated with at least 2 lines of chemotherapy; 11 patients (37%) with radiotherapy, 6 patients (20%) with autoHSCT while 4 patients (13%) with allogeneic (allo)HSCT. Six patients (20%) were resistant to previous salvage treatment. BGD therapy consisted of bendamustine 90mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1-4. Best response after at least 2 courses of therapy was the primary study end-point. Results. Median number of BGD cycles was 4 (2-7). Nineteen (63%) patients achieved complete remission (CR) confirmed by FDG-PET, while 6 patients (20%) achieved partial response (PR), accounting for 83% overall response (OR) rate. Stable disease was reported in 3 patients and progressive disease - in 2 cases. Many patients achieved CR (33%) or PR (33%) after 2 cycles of BGD. The OR rate was 85% for patients in whom BGD was administered as first salvage and 80% when used in more advanced stages of the disease. Fourteen patients proceeded to autoHSCT while 4 patients were subsequently treated with alloHSCT. Six patients experienced infections of the upper respiratory tract while two patients had allergic skin reactions. No organ toxicity was reported. One patient required transfusion of red blood cells while none was treated with platelet transfusions. Conclusion. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL. The protocol may be used as a bridge to autoHSCT or alloHSCT. Further, prospective studies are warranted to define its role in future treatment algorithms. Disclosures No relevant conflicts of interest to declare.

Bone and soft tissue malignancies

2015 ◽  
Author(s):  
Jim Cassidy ◽  
Donald Bissett ◽  
Roy A. J. Spence OBE ◽  
Miranda Payne ◽  
Gareth Morris-Stiff
Keyword(s):  
Myeloid Leukaemia ◽  
Hodgkin Lymphoma ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Current Treatment ◽  
Bisphosphonate Therapy ◽  
Heterogeneous Group ◽  
Low Grade ◽  
Quality Life

Haematological malignancies examines the epidemiology, genetics, clinical presentation and classification of these diseases, and presents current treatment approaches for each. First are the acute leukaemias, and the management of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Chronic myeloid leukaemia, its genetics and sensitivity to tyrosine kinase inhibitors, is described. Myelodysplastic syndromes and their management, are followed by chronic lymphoid leukaemias, a large heterogeneous group of diseases, and their treatment. Hodgkin lymphoma, its pathology and presentation, staging and role of PET scanning, is described along with current treatment with chemotherapy and limited radiotherapy. Non-Hodgkin lymphoma is another heterogeneous group of diseases, divided into low-grade and high-grade pathology, and varying in their genetics, presentation, and management. Rituximab is a key component of chemotherapy regimens against B-cell lymphoma. Myeloma and other plasma cell dyscrasias are described, and treatment options reviewed. Myeloma remains incurable, but with appropriate management consistent with prolonged good quality life. Treatment includes chemotherapy, bisphosphonate therapy, analgesics and radiotherapy, Throughout this chapter is emphasised the importance of clinical trials in driving the rapid improvements in treatment of these diseases.

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