scholarly journals FOLLICULAR LYMPHOMA: THE MANAGEMENT OF ELDERLY PATIENT

2016 ◽  
Vol 9 (1) ◽  
pp. e2017009 ◽  
Author(s):  
Alessia Castellino ◽  
Umberto Vitolo

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.

2016 ◽  
Vol 8 ◽  
pp. 2016061 ◽  
Author(s):  
Giuseppe Rossi ◽  
Antonella Anastasia

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.


2021 ◽  
Vol 5 (6) ◽  
pp. 1737-1745
Author(s):  
Carla Casulo ◽  
Jesse G. Dixon ◽  
Fang-Shu Ou ◽  
Eva Hoster ◽  
Bruce A. Peterson ◽  
...  

Abstract Limited data exist to describe the clinical features and outcomes for elderly patients with follicular lymphoma (FL). The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group performed a prospectively planned pooled analysis of individual patient data from first-line randomized controlled trials (RCTs) and examined associations between age (≤70 vs >70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (>70 years). Primary end points were early disease outcomes, CR24 and CR30, and progression-free survival (PFS) at 24 months (PFS24). Secondary end points were PFS and overall survival (OS). We identified 5922 previously untreated FL patients from 18 RCTs. Patients age >70 years (vs ≤70 years) more commonly had elevated lactate dehydrogenase, hemoglobin <12 g/dL, ECOG PS ≥2, and elevated β2-microglobulin. Median follow-up was 5.6 years. Patients >70 years did not differ from patients ≤70 years in rates of CR24, CR30, or PFS24. With a median OS of 14.6 years for all patients, median OS was 7.4 and 15.7 years for patients >70 and ≤70 years of age, respectively (hazard ratio = 2.35; 95% confidence interval = 2.03-2.73; P < .001). Age >70 years was a significant predictor of OS and PFS due to higher rates of death without progression, but not PFS24, CR24, or CR30. FL patients >70 years treated on trials have similar early disease outcomes to younger patients. There is no disease-specific outcome difference between age groups. Age alone should not disqualify patients from standard treatments or RCTs.


2021 ◽  
Vol 11 ◽  
Author(s):  
Mengya Zhong ◽  
Jinshui Tan ◽  
Guangchao Pan ◽  
Yuelong Jiang ◽  
Hui Zhou ◽  
...  

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.


Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 287-293 ◽  
Author(s):  
Victor A. Chow ◽  
Ajay K. Gopal

Abstract The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.


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 ◽  
...  

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).


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 670-670
Author(s):  
Veronika Bachanova ◽  
Daniel J. Weisdorf ◽  
Tao Wang ◽  
Steven G.E. Marsh ◽  
Elizabeth Trachtenberg ◽  
...  

Abstract While allogeneic donor hematopoietic cell transplantation (HCT) can cure non-Hodgkin lymphoma (NHL) by inducing a graft-versus-lymphoma effect, 10-35% of patients experience progression or relapse. We investigated whether the genotype of allogeneic donor natural killer (NK) cell killer immunoglobulin-like receptors (KIR) impacts the survival of lymphoma patients. The importance of KIR genetics in unrelated donor (URD) HCT has been demonstrated in AML where donors with favorable KIR gene content reduced the risk of relapse by 30%. Because the consequence of donor KIR genotype in NHL is unknown, we evaluated its effect on transplant outcome in 614 adults with NHL (28% follicular lymphoma, 16% diffuse large B cell lymphoma, 17% mantle cell lymphoma, 37% other) who underwent T cell replete URD HCT between 1990-2009 with outcomes reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Donor samples from the NMDP/CIBMTR Repository were genotyped (15 KIR genes) by MALDI-TOF mass spectroscopy. KIR haplotypes (A/A or B/x) were determined by presence/absence of individual KIR genes. Multivariate regression models were used to test the associations between donor KIR genotype and clinical outcome. The median patient age was 50 years (range 19-72), 93% were Caucasians and 62% had chemosensitive lymphoma. Most (60%) were >1.5 years from diagnosis; 41% received myeloablative preparative regimens and 61% received peripheral blood derived grafts. Most transplants were 10/10 matched for HLA alleles (n=396), the remainder 9/10 matched (n=158) or ≤8/10 matched (n=60). The frequencies of KIR genotypes in donors reflected the Caucasian population: 70% (n=428) were KIR B/x and 30% (n=180) were KIR A/A. Patients receiving 10/10 HLA-matched grafts (65%) experienced significantly lower relapse at 5 years when donors were KIR B/x genotype (n=281; 26% [95%CI 21-32%]) compared to KIR A/A genotype (n=115; 37% [95% CI 27-46%] ;p=0.05; Figure left) leading to improved progression-free survival (PFS) (35% [95% 26-44] vs. 22% [95%CI 11-35%]; p=0.02; Figure right). After adjusting for significant clinical variables, KIRB/x donors conferred significant protection against relapse (RR 0.63 [95%CI 0.43-0.92]; p=0.02) and improved PFS (RR 0.71 [95% CI 0.55-0.91]; p=0.008) compared to KIR A/A donors. The relapse protection and improved survival associated with KIR B/x donors was highly significant in the 10/10 HLA matched cohort (n=396) but not in the HLA-mismatched transplants (n=218; PFS RR 1.21 [95%CI 0.86-1.7]; Relapse RR 1.49 [0.87-2.55], p=NS for both). Importantly, the use of KIR B/x donors was associated with improved clinical outcomes for patients after both myeloablative and reduced intensity conditioning. Donor KIR genotype had no effect on rates of acute graft-versus-host disease (HR 1.05; p=0.86), and treatment related mortality at 1 year was similar for both groups (28% [B/x] and 30% [A/A]). In multivariate analysis of the entire cohort, other factors adversely impacting PFS included chemoresistant lymphoma (HR 1.52; p=0.03), disease other than follicular lymphoma (HR 1.34; p=0.0001) and <1.5 years interval from diagnosis to HCT (HR 1.35; p=0.003). Our results demonstrate that donors with KIR B/x genotypes, whose NK cells express more activating KIR, are associated with decreased relapse and improved survival after 10/10 HLA-matched URD HCT for NHL. The results suggest that NK cells may contribute to graft-versus-lymphoma effects and support the consideration of KIR genotyping with HLA typing into URD search criteria for patients with NHL. Figure 1 Figure 1. Disclosures Miller: Coronado: Speakers Bureau; BioSciences: Membership on an entity's Board of Directors or advisory committees; SAB: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.


2015 ◽  
Vol 33 (30) ◽  
pp. 3467-3474 ◽  
Author(s):  
Laurie H. Sehn ◽  
Andre Goy ◽  
Fritz C. Offner ◽  
Giovanni Martinelli ◽  
M. Dolores Caballero ◽  
...  

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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4119-4119
Author(s):  
J. Feliu ◽  
M. Safont ◽  
A. Salud ◽  
F. Losa ◽  
C. García-Girón ◽  
...  

4119 Background: Colorectal adenocarcinoma is the most common cancer in subjects over 70 years old. New therapies have been developed but limited data about their activity are available in elderly population. Results obtained with capecitabine have shown an appropriate safety and efficacy profile in these patients. The aim of the present study is to evaluate the overall response rate in that patient's population who presents colorectal adenocarcinoma and are treated with the combination of capecitabine+BVZ. Methods: This is a multicentric, non-controlled, open label, phase II clinical trial. Capecitabine(1250mg/m2 bid, orally)+BVZ(7.5mg/kg, intravenously) treatment was administered in 3-week length cycles until disease progression. Capecitabine dose was reduced to 1000mg/m2 when the creatinine clearance was between 30 and 50ml/min. Results: A total of 59 patients were included (57.6%, male). Mean age was 76±4.1 years. ECOG status was 0–1 in 96.5 % of the patients. Activities of daily living: moderate to severe dependence and functional incapacity in 24.5% and 5.6% of the patients by Lawton and Barthel scales, respectively. Comorbidities: hypertension (61%), venous thrombosis (5.1%), cardiac disease (5.1%) and acute cerebrovascular accident history (3.4%). Metastases were detected in liver (84.7%), lung (45.8%), local/regional (18.6%) and other locations (5.1%). Mean number of cycles of capecitabine+BVZ was 6.8±6.1. Most frequent grade 3–4 toxicities observed were hand-foot-syndrome (18.6%), diarrhea (8.5%), deep venous thrombosis (6.8%), pain (5.1%) and mucositis (3.4%). Four patients died due to toxicity (mucositis, digestive hemorrhage, hematological toxicity and sepsis, respectively). Metastasis resection was performed in 10.2% of the patients. Treatment response was: 33.3% partial response and 59.0% stable disease. Median progression-free survival was 10.8 months. Conclusions: The combination capecitabine+BVZ in elderly patients appears to have a manageable safety profile and achieves promising results in terms of response rates and progression free-survival. No significant financial relationships to disclose.


2005 ◽  
Vol 23 (33) ◽  
pp. 8447-8452 ◽  
Author(s):  
Richard I. Fisher ◽  
Michael LeBlanc ◽  
Oliver W. Press ◽  
David G. Maloney ◽  
Joseph M. Unger ◽  
...  

Background The natural history of follicular lymphoma is believed not to have changed over the last 30 years. Median survivals have ranged from 7 to 10 years, and the disease is considered incurable. However, multiple new treatment options have been developed in the last decade, and their impact on survival of follicular lymphoma remains unknown. Patients and Methods In the current analysis, we identified all previously untreated, advanced-stage, follicular lymphoma patients treated with the following three sequential treatment approaches: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy ± nonspecific immunostimulants (Southwest Oncology Group [SWOG] 7426 and 7713: 1974 to 1983); prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide (ProMACE) plus mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) ± interferon (SWOG 8809: 1988 to 1994); and CHOP followed by monoclonal antibody (MoAb) therapy (SWOG 9800 and 9911: 1998 to 2000). We assessed the patients' progression-free survival (PFS) and overall survival (OS). The MoAb trials included CHOP followed by rituximab (SWOG 9800) and CHOP followed by 131I-tositumomab (SWOG 9911). Results The PFS curves for the CHOP and ProMACE-MOPP studies are overlapping, with 4-year PFS estimates of 46% and 48%, respectively. However, the PFS rate of the CHOP + MoAb studies is significantly improved at 61% (P = .005). The OS curves show improvement with each succeeding study. The 4-year estimate of OS is 69% for the CHOP regimens, 79% for the ProMACE-MOPP study, and 91% for the CHOP + MoAb regimens (P < .001). These conclusions were retained after adjusting for differences in prognostic factors between the study groups. Conclusion The results of this study suggest that OS for patients with follicular lymphoma has improved over time and that the choice of initial therapy may matter.


Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 285-296
Author(s):  
Alfred Reiter

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.


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