scholarly journals NOVEL DRUGS IN FOLLICULAR LYMPHOMA

2016 ◽  
Vol 8 ◽  
pp. 2016061 ◽  
Author(s):  
Giuseppe Rossi ◽  
Antonella Anastasia
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Free Treatment ◽  
Phase Iii Trials ◽  
New Treatment ◽  
Anti Cd20 ◽  
Key Steps

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of a chieving a definite cure, have prompted investigations into the possible role of more effective and less toxic strategies with innovative therapeutic agents.  Recently Casulo et al demonstrated that approximately 20% of patients with FL actually relapse within 2 years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis.Evolving strategies for difficult to treat FL patients have recently considered  immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), with mAbs directed against other surface antigens such as CD22 and CD23 (epratuzumab, lumiliximab), with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inibithors(idelalisib, duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies,  taking into account their toxicity. Of course we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

scholarly journals Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study

2015 ◽  
Vol 33 (30) ◽  
pp. 3467-3474 ◽  
Author(s):  
Laurie H. Sehn ◽  
Andre Goy ◽  
Fritz C. Offner ◽  
Giovanni Martinelli ◽  
M. Dolores Caballero ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hodgkin Lymphoma ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Indolent Lymphoma ◽  
Previous Response ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20+ indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m2). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm. Conclusion Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials.

scholarly journals FOLLICULAR LYMPHOMA: THE MANAGEMENT OF ELDERLY PATIENT

2016 ◽  
Vol 9 (1) ◽  
pp. e2017009 ◽  
Author(s):  
Alessia Castellino ◽  
Umberto Vitolo
Keyword(s):  
Elderly Patients ◽  
Follicular Lymphoma ◽  
Randomized Clinical Trials ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Mature Adults ◽  
Non Hodgkin Lymphoma ◽  
Incurable Disease ◽  
New Treatment

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, typically affected mature adults and elderly, with a median age at diagnosis of 65 years. The natural history of FL appears to have been favorably impacted by the introduction of Rituximab. Randomized clinical trials have demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival and new strategies of chemo-immunotherapy, such as Bendamustine combined with Rituximab, showed optimal results on response and lower hematological toxicity, becoming one of the standard treatments, particularly in elderly. Moreover maintenance therapy with Rituximab demonstrated improvement of progression-free survival. Despite these exciting results, FL is still an incurable disease. It remains a critical unmet clinical need finding new prognostic factors to better identify poor outcome patients, to reduce the risk of transformation and to explore new treatment strategies, especially for patients not candidate to intensive chemotherapy regimens, such as elderly patients. Some progresses were already done with novel agents, but larger and more validated studies are needed. Elderly patients are the larger portion of patients with FL and represent a subgroup with higher treatment difficulties, because of comorbidities and smaller spectrum for treatment choice. Further studies, focused on elderly follicular lymphoma patients, with their peculiar characteristics, are needed in order to define the best tailored treatment at diagnosis and at the time of relapse in this setting.

scholarly journals Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Mengya Zhong ◽  
Jinshui Tan ◽  
Guangchao Pan ◽  
Yuelong Jiang ◽  
Hui Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Follicular Lymphoma ◽  
Single Agent ◽  
Hdac Inhibitors ◽  
Treatment Strategies ◽  
Annexin V ◽  
Gene Encoding ◽  
New Treatment ◽  
Transformed Follicular Lymphoma

The key factors leading to transformed follicular lymphoma (t-FL) include the aberrations of epigenetic modifiers as early and driving events, especially mutations in the gene encoding for histone acetyltransferase. Therefore, reversal of this phenomenon by histone deacetylase (HDAC) inhibitors is essential for the development of new treatment strategies in t-FL. Several t-FL cell lines were treated with various doses of chidamide and subjected to cell proliferation, apoptosis and cell cycle analyses with CCK-8 assay, Annexin V/PI assay and flow cytometry, respectively. Chidamide dose-dependently inhibited cell proliferation, caused G0/G1 cycle arrest and triggered apoptosis in t-FL cells. In addition, the effects of chidamide on tumor growth were evaluated in vivo in xenograft models. RNA-seq analysis revealed gene expression alterations involving the PI3K-AKT signaling pathway might account for the mechanism underlying the antitumor activity of chidamide as a single agent in t-FL. These findings provide a basis for further clinical exploration of chidamide as a promising treatment for FL.

scholarly journals Chronic lymphocytic leukemia paradigm continues to be refined: news from the American Society of Hematology 2018 annual meeting

2019 ◽  
Vol 8 (2) ◽  
pp. IJH14
Author(s):  
Stefano Molica
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Standard Of Care ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
Prospective Phase ◽  
American Society ◽  
Anti Cd20

There were a number of important updates and advances presented at the 2018 Annual American Society of Hematology meeting. With respect to the treatment of chronic lymphocytic leukemia, the American Society of Hematology 2018 was notable for an improved understanding of ibrutinib-based therapies. In fact, three prospective Phase III trials presented at the meeting indicate, in turn, that ibrutinib alone, ibrutinib plus rituximab, or ibrutinib plus obinutuzumab, should be the new standard of care for chronic lymphocytic leukemia. However, additional clinical trials comparing chemo-immunotherapy with ibrutinib alone or in association with an anti-CD20 monoclonal antibody remain a reasonable avenue to complete results of these large studies.

A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1606-1612 ◽  
Author(s):  
Oliver W. Press ◽  
Joseph M. Unger ◽  
Rita M. Braziel ◽  
David G. Maloney ◽  
Thomas P. Miller ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Oncology Group ◽  
Chop Chemotherapy ◽  
Southwest Oncology Group ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Trial ◽  
Main Adverse Event ◽  
Anti Cd20

AbstractAdvanced follicular lymphoma is incurable with conventional chemotherapy and radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase 2 trial (S9911) of a novel regimen consisting of 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed 4 to 8 weeks later by tositumomab/iodine I 131 tositumomab (anti-CD20 antibody) in 90 eligible patients with previously untreated, advanced stage follicular lymphoma. Treatment was well tolerated. Reversible myelosuppression was the main adverse event and was more severe during CHOP chemotherapy than following radioimmunotherapy. The overall response rate to the entire treatment regimen was 90%, including 67% complete remissions (CRs plus unconfirmed CRs [CRu's]) and 23% partial remissions (PRs). Twenty-seven (57%) of the 47 fully evaluable patients who achieved less than a CR with CHOP improved their remission status after tositumomab/iodine I 131 tositumomab. With a median follow-up of 2.3 years, the 2-year progression-free survival (PFS) was estimated to be 81%, with a 2-year overall survival of 97%. This study has established the feasibility, tolerability, and efficacy of this regimen for patients with advanced follicular lymphoma. This novel treatment appears promising compared with the SWOG's historical experience using CHOP alone and is currently being compared with CHOP plus rituximab in a randomized phase 3 trial (S0016).

Treatment with the Anti-CD20 Antibody (B1) and Irradiation Result in Synergistic Cytotoxicity That Is Dependent on MAPK Activation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2508-2508
Author(s):  
Andrei Ivanov ◽  
Mark S. Cragg ◽  
Tim M. Illidge
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Death Receptor ◽  
Clonogenic Survival ◽  
Lymphoma Cell ◽  
Non Hodgkin Lymphoma ◽  
Morphological Studies ◽  
Synergistic Cytotoxicity ◽  
New Treatment ◽  
Anti Cd20

Abstract Radioimmunotherapy using radiolabeled anti-CD20 antibodies (mAb) is an effective new treatment in non-Hodgkin lymphoma with high response rates. However, the molecular mechanisms behind these impressive clinical responses are poorly understood. To elucidate these mechanisms we studied the signaling events evoked in a panel of lymphoma cell lines following treatment with anti-CD20 mAb alone or in combination with irradiation. In all three lymphoma cell-lines tested a synergistic cytotoxic effect was observed when the anti-CD20 mAb B1 was combined with irradiation. The additive effect seen with B1 mAb and radiation was not observed with Rituximab and could be reversed with MEK inhibitors U0126 and PD98059 as well as siRNA targeting MEK1 or 2. Moreover, addition of U0126 reversed the decrease in clonogenic survival triggered by treatment with B1 and irradiation. To further probe the mechanism of this synergistic cell death we used cell lines over-expressing BCL2 or crmA, to block mitochondrial and death receptor pathways, respectively. Although BCL2 and crmA over-expression mediated protection against radiation alone, it had no impact on the increased cytotoxicity induced by B1+irradiation. Morphological studies revealed gross vacuolization of the cytoplasm, yet relatively well preserved nuclei in cells treated with B1+irradiation. Taken together our data indicate that activation of the MAPK cascade is an important factor that contributes to the synergistic effect of anti-CD20 (B1) antibody and irradiation and provides important new insights into how this treatment may work in the clinic.

scholarly journals Prospects in the management of patients with follicular lymphoma beyond first-line therapy

Haematologica ◽  
2022 ◽  
Vol 107 (1) ◽  
pp. 19-34 ◽  
Author(s):  
David Qualls ◽  
Gilles Salles
Keyword(s):  
Follicular Lymphoma ◽  
Kinase Inhibitors ◽  
Treatment Strategies ◽  
Cytotoxic Agents ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Phase Ii Studies ◽  
Clinical Scenarios ◽  
Histological Transformation ◽  
Anti Cd20

The management of patients with relapsed or refractory follicular lymphoma has evolved markedly in the last decade, with the availability of new classes of agents (phosphoinositide 3-kinase inhibitors, immunomodulators, epigenetic therapies, and chimeric antigen receptor T cells) supplementing the multiple approaches already available (cytotoxic agents, anti-CD20 antibodies, radiation therapy, radioimmunotherapy, and autologous and allogeneic transplants). The diversity of clinical scenarios, the flood of data derived from phase II studies, and the lack of randomized studies comparing treatment strategies preclude firm recommendations and require personalized decisions. Patients with early progression require specific attention given the risk of histological transformation and their lower response to standard therapies. In sequencing therapies, one must consider prior treatment regimens and the potential need for future lines of therapy. Careful evaluation of risks and expected benefits of available options, which vary depending on location and socioeconomics, should be undertaken, and should incorporate the patient’s goals. Preserving quality of life for these patients is essential, given the likelihood of years to decades of survival and the possibility of multiple lines of therapy. The current landscape is likely to continue evolving rapidly with other effective agents emerging (notably bispecific antibodies and other targeted therapies), and multiple combinations being evaluated. It is hoped that new treatments under development will achieve longer progression-free intervals and minimize toxicity. A better understanding of disease biology and the mechanisms of these different agents should provide further insights to select the optimal therapy at each stage of disease.

scholarly journals Bendamustine in the treatment of B-cell non-Hodgkin lymphoma

2018 ◽  
Vol 20 (4) ◽  
pp. 41-46
Author(s):  
L G Babicheva ◽  
I V Poddubnaya
Keyword(s):  
Clinical Data ◽  
Therapeutic Index ◽  
Daily Practice ◽  
Phase Iii ◽  
Cross Resistance ◽  
Skin Reactions ◽  
Non Hodgkin Lymphoma ◽  
Antiemetic Prophylaxis ◽  
Mantle Cell ◽  
Phase Iii Trials

Bendamustine is a uniquely structuredalkylating agent that lacks cross-resistance with other alkylators. This agent has a high degreeof activity against a variety of tumor cell lines.Based on clinical data from randomized phase III trials, bendamustine, with or without rituximab, hasbeen shown to be an appropriate option for first-line treatment or treatment of relapsed/refractory patients with indolent non-Hodgkin’s lymphoma or elderly patients with mantle cell lymphoma. Bendamustine treatment is associated with abetter therapeutic index and offers an improved overall quality of life compared to R-CHOP or R-CVP. It is now often used as achemotherapy backbone for combination with novel drugs including ibrutinib or idelalisib. This article provides a comprehensivesummaryof the clinical data along with practical adviceonhowto optimallymanagepatients with bendamustine therapy, includingdose recommendations, antiemetic prophylaxis, prevention of infusion and skin reactions, as well as prophylaxis of opportunisticinfections. This information might be helpful for clinicians using bendamustine in their daily practice.

scholarly journals Diagnosis and Treatment of Childhood Non-Hodgkin Lymphoma

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 285-296
Author(s):  
Alfred Reiter
Keyword(s):  
Hodgkin Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Large Cell ◽  
Salvage Regimen ◽  
Treatment Groups ◽  
Non Hodgkin Lymphoma ◽  
Appropriate Treatment ◽  
New Treatment

Major advances have been made in the treatment of childhood non-Hodgkin lymphoma (NHL). The recognition that different NHL subtypes require different treatment strategies was fundamental to developing successful therapy regimens. Currently established therapy groups are lymphoblastic lymphoma (LBL) of precursor B- or T-cell type, mature B-cell neoplasms (B-NHL), and anaplastic large cell lymphoma (ALCL). Accurate diagnostic classification is crucial for allocating patients to appropriate treatment groups. Therapy protocols designed to treat children with acute lymphoblastic leukemia (ALL) have proven highly efficacious for treating children with LBL and are associated with event-free survival (EFS) rates up to 80%. For children with B-NHL, a strategy of rapidly repeated short, dose-intense courses proved more efficacious, with EFS rates up to 90%. In patients with ALCL, comparable results are achieved with either strategy, although this group has the highest relapse rate. The price of these efficacious treatments is considerable toxicity. On the other hand, the chance to survive after relapse is still dismal due to the almost complete lack of established salvage regimen. Thus, refinement of the balance between treatment burden and individual patient risk for failure is a major future task. A variety of new treatment options, some already established for treating adult NHL, await evaluation in childhood NHL.

The Use of Gene-Expression Profiling to Predict Outcome of Follicular Lymphoma Patients Treated with Rituximab and Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1395-1395
Author(s):  
Antti Harjunpää ◽  
Matti Nykter ◽  
Outi Monni ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Samuli Hemmer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Follicular Lymphoma ◽  
Expression Patterns ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Feature Selection Method ◽  
Risk Groups ◽  
Gene Predictor ◽  
Anti Cd20

Abstract The anti-CD20 monoclonal antibody rituximab has been extensively evaluated for treatment of follicular lymphoma (FL) and is now an integral component of many treatment strategies. However, it is not known when and how to use this combination modality best in the overall treatment course of FL patients. Here we have analyzed the pattern of gene expression in lymph nodes from 28 FL patients who received rituximab in combination with chemotherapy. We demonstrate a novel feature selection method, in which genes whose expression correlates with treatment outcome are devided into groups based on similar expression patterns. By selecting representatives from these groups we built a three-gene predictor (for example RRAD, MGC5254, MARCO) which turned out to be successful in classifying all 28 samples correctly with respect to the responders versus nonresponders distinction. A similar four-gene predictor (for example USP9Y, CUL-4B, NSFS/REST, MADH) correctly classified the responding patients into two subgroups with very different event-free survival rates at the median follow up of 21 months (median not reached vs. 15 months, p<0.0001). The latter predictor also efficiently delineated patients within specific FLIPI risk groups. Our data demonstrate the ability of these microarray-based predictors to classify FL patients treated with rituximab and chemotherapy to subgroups with significantly distinct outcomes.

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