Clinical observation of pediatric-type follicular lymphomas in adult:Two case reports

BACKGROUND Pediatric-type follicular lymphoma(PTFL)is a unique pathological type in the 4th edition of hematopoiesis and lymphoid tissue tumor classification revised by World Health Organization.It is unique in clinical practice and seldom seen in adult.PTFL mainly occurs in the head and neck lymph nodes.Most of the cases are short of fever,night sweat,weight loss,and other B symptoms which substitute for lymphadenopathy as the main symptom.PTFL can be disposed of surgical resection and it can achieve long-term tumor-free survival,and it has an excellent outcome.CASE SUMMARY Two cases of PTFL were reported and their clinicopathological features,differential diagnosis,therapy and prognosis were discussed.PTFL showed graybrown tough texture in general performance.The histological manifestations of PTFL were similar to that of adult-follicular lymphoma(FL).Under low power microscope,the structure of lymph nodes was destroyed in different degree,the follicles were closely arranged,expanded and irregular,and the mantle zone became thin or disappeared.In addition,the“starry sky phenomenon”could be seen.At high magnification,the follicles were mainly composed of single medium-sized central cells,and some of them mainly consisted of centroblastic cells to characterize scattered chromatin and inconspicuous nucleoli.Immunohistochemical showed the tumor cells expressed CD20,PAX5,CD79a and CD10,BCL6,FOXP-1,which were limited in germinal center;Ki-67 was highly expressed in germinal center.CD21 and CD23 showed nodular and expanded follicular dendritic cells.Immunoglobulin gene rearrangement was positive for IGH and IGK.The two patients underwent surgical resection with no complications.After discharge,the two patients with a close review for 18 mo and 5 mo respectively and showed no evidence of recurrence.CONCLUSION PTFL in adult is generally supposed to be extremely rare.PTFL displayed characteristic morphological,immunophenotypic,and molecular biological changes which are a kind of neoplasm with satisfactory prognosis after surgical excision.

Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas

Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.

Efficacy and safety of Revlimid combined with Rituximab in the treatment of follicular lymphoma: A meta-analysis

Objective:To evaluate the clinical efficacy and safety of lenalidomide combined with rituximab for treating follicular lymphoma.Methods:We searched PubMed,Web of Science,Cochrane Library,Embase,China Medical Biological Service system(CBM),VIP database(VIP),Wan fang database(Wan Fang Data),China Knowledge Network(CNKI),and ClinicTrails.gov for literature related to lenalidomide combined with rituximab for treating follicular lymphoma(until June 23,2022).The literature that met the requirements were screened out according to the established criteria,and the data were analyzed by RevMan5.4 and Stata14.0 to conduct a meta-analysis.Results:Eight studies involving 865 patients with follicular lymphoma were included.The results of the meta-analysis showed that the objective remission rate(RR=1.43,95%CI:1.26–1.61)and complete remission rate(RR=1.67,95%CI:1.27–2.21)of lenalidomide combined with rituximab for treating follicular lymphoma were significantly higher than those of rituximab alone.However,adverse reactions(neutropenia,diarrhea,nausea and vomiting,rash)were more likely to occur in the lenalidomide combined with the rituximab group,albeit at a low level.Conclusion:Compared to rituximab alone,lenalidomide combined with rituximab could significantly improve the objective and complete remission rates of patients with follicular lymphoma.However,as combination therapy may be associated with adverse reactions,timely corresponding measures should be taken during treatment.Therefore,to confirm the efficacy and safety of lenalidomide combined with rituximab for treating follicular lymphoma,it is necessary to conduct multicenter,multi-sample,randomized double-blind controlled trials,and single-arm trials.

Duodenal-type follicular lymphoma more than 10 years after treatment intervention:A retrospective single-center analysis

BACKGROUND Duodenal-type follicular lymphoma(D-FL)has been recognized as a rare entity that accounts for approximately 4%of primary gastrointestinal lymphomas.D-FL follows an indolent clinical course compared with common nodal FL and is generally considered to have a better prognosis.Therefore,the“watch and wait”approach is frequently adopted as the treatment method.Alternatively,there is an option to actively intervene in D-FL.However,the long-term outcomes of such cases are poorly understood.AIM To clarify the clinical outcomes after long-term follow-up in cases of D-FL with treatment intervention.METHODS We retrospectively analyzed patients who met the following criteria:the lesion was confirmed by endoscopy,the diagnosis of D-FL was confirmed histopathologically,and the patient was followed-up for more than 10 years after the intervention at our center.RESULTS We identified 5 cases of D-FL.Two patients showed a small amount of bone marrow involvement(Stage IV).Rituximab was used as a treatment for remission in all 5 patients.It was also used in combination with chemotherapy in 2 Stage IV patients as well as for maintenance treatment.Radiation therapy was performed in 2 cases,which was followed by complete remission(CR).Eventually,all 5 patients achieved CR and survived for more than 10 years.However,3 patients experienced recurrence.One patient achieved a second CR by retreatment,and in another case,the lesion showed spontaneous disappearance.The remaining patient had systemic widespread recurrence 13 years after the first CR.Biopsy results suggested that the FL lesions were transformed into diffuse large B-cell lymphoma.The patient died 4 years later despite receiving various chemotherapies.CONCLUSION In this study,the treatment for patients of D-FL in Stage IV was successful.In the future,criteria for how to treat“advanced”D-FL should be established based on additional cases.This study of patients with D-FL indicates that whole-body follow-up examinations should continue for a long time due to a fatal recurrence 13 years after reaching CR.

Treatment strategies for nodal and gastrointestinal follicular lymphoma:Current status and future development

In recent years,therapies for follicular lymphoma (FL) have steadily improved.A series of phase Ⅲ trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival.Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy.For patients with relapsed or refractory FL,phase Ⅱ studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS),oblimersen sodium (a Bcl-2 antisense oligonucleotide),bendamustine,and rituximab,as well as veltuzumab,a new humanized anti-CD20 antibody,and epratuzumab.In addition,the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported.Furthermore,three phase Ⅲ studies on an idiotype vaccine are near completion.Unfortunately,these vaccines,which appeared highly effective in phase Ⅰ and Ⅱ trials,do not appear to result in prolonged PFS.This report will summarize the current knowledge on therapies for treatment of FL,and will conclude with a brief discussion of feasiblefuture options for effective treatments.Lastly,we added descriptions of the management of gastrointestinal FL,which is considered to be controversial because it is rare.

Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.

Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

AIM:To investigate the capacity for 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography(PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma.METHODS:This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011.Data for endoscopic,radiological,and biological examinations performed were retrospectively reviewed from clinical records.A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value(SUVmax).Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed,patients were subdivided into two groups.To identify potential predictive factors for 18F-FDG positivity,these two groups were compared with respect to gender,age at diagnosis of lymphoma,histopathological grade,pattern of follicular dendritic cells,mitotic rate,clinical stage,soluble interleukin-2 receptor levels detected by 18F-FDG-PET,lactate dehydrogenase(LDH) levels,hemoglobin levels,bone marrow involvement,detectability of gastrointestinal lesions by computed tomography(CT) scanning,and follicular lymphoma international prognostic index(FLIPI) risk.RESULTS:Involvement of follicular lymphoma in the stomach,duodenum,jejunum,ileum,cecum,colon,and rectum was identified in 1,34,6,3,2,3,and 6 patients,respectively.No patient had esophageal involvement.In total,19/41(46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract.In contrast,false-negative 18F-FDG uptake was detected in 24 patients(58.5%),while false-positive 18F-FDG uptake was detected in 5 patients(12.2%).In the former case,2/19 patients had both 18F-FDG-positive lesions and 18F-FDGnegative lesions in the gastrointestinal tract.In patients with 18F-FDG avidity,the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4(median:4.7).For the 18F-FDG-negative(n = 22) and-positive(n = 19) groups,there were no differences in the male to female ratios(10/12 vs 4/15,P = 0.186),patient age(63.6 ± 2.4 years vs 60.1 ± 2.6 years,P = 0.323),presence of histopathological grade 1 vs 2(20/2 and 17/2,P = 1.000),follicular dendritic cell pattern(duodenal/nodal:13/5 vs 10/3,P = 1.000),mitotic rate(low/partly high,14/1 vs 10/3,P = 0.311),clinical stage according to the Ann Arbor system(stages ⅠE and ⅡE/other,15/7 vs 15/4,P = 0.499),clinical stage according to the Lugano system(stages Ⅰ and Ⅱ-1/other,14/8 vs 14/5,P = 0.489),soluble interleukin-2 receptor levels(495 ± 78 vs 402 ± 83,P = 0.884),LDH levels(188 ± 7 vs 183 ± 8,P = 0.749),hemoglobin levels(13.5 ± 0.3 vs 12.8 ± 0.4,P = 0.197),bone marrow involvement(positive/negative,1/8 vs 1/10,P = 1.000),detectability by CT scanning(positive/negative,1/16 vs 4/13,P = 0.335),and FLIPI risk(low risk/other,16/6 vs 13/6,P = 0.763),respectively in each case.CONCLUSION:These findings indicate that it is not feasible to predict 18F-FDG-avidity.Therefore,18FFDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients,and surveillance of the entire gastrointestinal tract by endoscopic examinations is required.

A Single Fusion Signal for t(14;18)(q32;q21) Translocation Is Present in Both the Follicular Lymphoma and Local Endothelial Cells

Herein we reported a case of follicular lymphoma with 50.26% clonal malignant lymphocytes and 50% tumor cells positive for the immunoglobulin heavy chain gene and B-cell lymphoma 2 gene （IGH-BCL2）. To determine whether endothelial cells （ECs） within the tumor share the feature of advanced malignancy, we isolated and purified the ECs from the tumor by using the immunomagnetic beads conjugated with a monoclonal antibody against CD34, a surface marker of ECs. Thereafter, we identified ECs according to their morphology and found that ECs presented consistently flat and elongated appearance with a lot of Weibel-Palade bodies in the cytoplasm. Results of flow cytometry confirmed that ECs isolated from the follicular lymphoma expressed high level of both vWF and CD34 and the purity of the ECs fraction was more than 90%. Additionally, we used FISH to check chromosomal aberration in the purified ECs and found that some of the ECs had only one fusion signal for the green IGH probe and the red BCL2 probe in contrast to typical t（14;18）（q32;q21） translocation with two fusion signals. This phenomenon was also observed in the tumor cells. It might be a different breakpoint of IGH in this case, which induced the loss of the fusion signal, indicating t（14;18）（q32;q21） translocation. The positive cells accounted for 18% of the isolated ECs from the tumor, indicating that a proportion of ECs from follicular lymphoma had the same chromosome aberration as the neoplastic cells.

Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center:A retrospective analysis

BACKGROUND Follicular lymphoma(FL)is a type of B-cell lymphoma that originates at the germinal center and has a low malignancy rate.FL has become the most common inert lymphoma in Europe and America but has a relatively low incidence in Asia.AIM To explore the clinical features,curative effects,and prognostic factors of FL.METHODS Completed medical records of 49 patients with FL who were admitted to the Ningbo First Hospital from June 2010 to June 2021 were examined.These patients were definitively diagnosed by pathological biopsy or immunohistochemical staining.The diagnostic criteria were based on the 2008 World Health Organization classification of lymphomas.Ann Arbor staging was performed according to the imaging and bone marrow examination results.Risk stratification of all patients was performed based on the International Prognostic Index(IPI),age-adjusted IPI,Follicular Lymphoma International Prognosis Index(FLIPI),and FLIPI2 to compare the efficacy of different treatment regimens and analyze the related prognostic factors.RESULTS The age of onset in patients ranged from 24 to 76 years,with a median age of 51 years.Most patients developed the disease at 40–59 years of age,and the male:female ratio was 1.6:1.No significant difference was noted in the curative effect between the non-chemotherapy,combined chemotherapy,and other chemotherapy regimens(P>0.05).Hemoglobin(Hb)level<120 g/L,Ki-67 value>50%,bone marrow involvement,and clinical stagesⅢ–IV were associated with a poor prognosis of FL(P<0.05).However,the influence of other indicators was not statistically significant.Risk grouping was performed using the FLIPI,and the results showed that 24.5%,40.8%,and 34.7%of patients were in the low-,moderate-,and high-risk groups,respectively.According to the survival analysis results,the survival rate of patients was lower in the high-risk group than in the other low-risk and moderate-risk groups(P<0.05).CONCLUSION FL mainly occurs in middle-aged and elderly men,primarily affecting lymph nodes and bone marrow.Hb level,Ki-67 value,bone marrow involvement,and clinical staging were used to evaluate prognosis.

Primary follicular lymphoma in the renal pelvis:A rare case report

BACKGROUND Follicular lymphoma(FL)is more common in lymph nodes,while primary extranodal lymphomas are rare.Urinary tract lymphoid neoplasms are extremely rare,accounting for less than 5%of all extranodal lymphomas.Only one case of FL from the renal pelvis has previously been reported.CASE SUMMARY A 70-year-old male patient with a history of esophageal cancer visited our hospital for follow-up examination.Abdominal computed tomography revealed a malignant mass in the right renal pelvis.The whole-body positron emission tomography/computed tomography showed a significant increase in fluorodeoxyglucose uptake of this soft tissue mass and no abnormal fluorodeoxyglucose uptake in the esophageal wall.The patient underwent radical resection of a malignant tumor in the right kidney,which was confirmed by postoperative pathology to be FL.The patient received no radiation or chemotherapy after surgery,and no recurrence of lymphoma or other malignant tumors was found at the 1-year follow-up.CONCLUSION Extranodal FL is more common in the skin and gastrointestinal tract but rarely occurs in the urinary tract.This is the second report of primary renal FL.Localized extranodal FL is expected to have a favorable prognosis and can be cured by local resection.

Detection of BCL2-IGHrearrangement on paraffin-embedded tissue sections obtained from a small submucosal tumor of the rectum in a patient with recurrent follicular lymphoma

A 59-year-old woman was admitted to our hospital because of recurrent follicular lymphoma(FL).Colonoscopic examination revealed a rectal submucosal tumor(SMT)without any erosions and ulcers.In this patient,it was difficult to distinguish non-Hodgkin's lymphoma(NHL)invasion from other disorders of the colon including carcinoid tumor merely based on endoscopic findings.Histopathologic and immunohistochemical studies on biopsy specimens showed an infiltration of atypical lymphocytes that were positive for CD20 and BCL2 but negative for UCHL-1.Fluorescence in situ hybridization on paraffin-embedded tissue sections (T-FISH)identified a translocation of BCL2 with IGHgene. Based on these findings,the tumor was defined as an invasion of FL.T-FISH method is useful for the detection of a monoclonality of atypical lymphocytes in an SMT of the gastrointestinal tract,and particularly for the detection of chromosomal translocations specific to lymphoma subtypes.

Low symptomatic COVID-19 in an elderly patient with follicular lymphoma treated with rituximab-based immunotherapy:A case report

BACKGROUND Follicular lymphoma is an indolent lymphoma that may progress to a highly aggressive form requiring immunochemotherapy.Most regimens utilize rituximab,an anti-CD20 monoclonal antibody,which may affect the clinical course of novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections[coronavirus disease 2019(COVID-19)].Here we describe the first case of mild COVID-19 during ongoing oncological treatment without significant deterioration after rituximab administration.CASE SUMMARY A 74-year-old female with an enlargement of her right palatine tonsil was diagnosed with follicular lymphoma following tonsillectomy and started immunochemotherapy according to the rituximab,cyclophosphamide,vincristine,prednisone regimen.At home before the fourth cycle,she developed nonspecific symptoms(excessive fatigue,loss of appetite and nausea),misdiagnosed as adverse effects of chemotherapy.Unexpectedly,interim positron emission tomography-computed tomography scan,performed shortly before rituximab administration,revealed previously nonexistent pulmonary changes,potentially of infectious etiology.SARS-CoV-2 infection was confirmed by a nasopharyngeal swab(with reverse transcriptase polymerase chain reaction test)performed the following day.Despite rituximab infusion,the patient remained oligosymptomatic and was discharged home for self-isolation.Having reached a negative SARS-CoV-2 status before the subsequently scheduled regimen,the patient successfully received six cycles of rituximab,cyclophosphamide,vincristine,prednisone and obtained complete remission by positron emission tomographycomputed tomography.CONCLUSION Our case shows that rituximab-based immunotherapy due to follicular lymphoma may have no evident negative effect on the COVID-19 clinical course.

Follicular lymphoma presenting like marginal zone lymphoma:A case report

BACKGROUND Follicular lymphoma(FL),a common type of indolent lymphoma,carries markers of the germinal center,and the rearrangement of the BCL-2 gene is regarded as an initiating event and a hallmark of the neoplasm.When FL has marginal zone differentiation,some marginal zone features are carried by the neoplasm.CASE SUMMARY A 54-year-old male with lymphadenopathy,splenomegaly and hyperlymphocytosis was diagnosed with FL with marginal zone differentiation.The tumor demonstrated different features in the bone marrow(BM)compared with the follicle of the lymph node(LN).Some component of the neoplasm mimicked marginal zone lymphoma,such as infiltrating the marginal zone of the LN,displaying a monocytoid shape and lacking the expression of CD10 in the BM.The diagnosis of FL was made due to the concurrent detection of BCL-2 rearrangement in the LN and BM.CONCLUSION Discordant pathological features in LN and BM could mislead diagnosis.When clinical and pathological manifestations are confusing in diagnosis,typical genetic abnormalities are decisive.

Pediatric-type follicular lymphoma in a Crohn’s disease patient receiving anti-α4β7-integrin therapy:A case report

BACKGROUND Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas(NHL).Vedolizumab(anti-α4β7-integrin antibody),a treatment-of-choice for Crohn’s disease(CD),reduces inflammatory lymphocyte trafficking into the intestinal mucosa.This effect is believed to be confined to the colon.CASE SUMMARY We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma.Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens.Rituximab,cyclophosphamide,vincristine,and prednisone chemoimmunotherapy resulted in durable lymphoma remission,and vedolizumab treatment was continued.While the patient’s T-lymphocyte population and immunoglobulin production recovered,the T-lymphocyte mitogen response remained suppressed.CONCLUSION This patient’s NHL may be linked to receiving anti-α4β7 therapy.Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.

Follicular lymphoma with cardiac involvement in a 90-year-old patient:A case report

BACKGROUND The incidence of cardiac lymphoma is low,and it mainly occurs secondary to nonHodgkin’s lymphoma,particularly diffuse large B-cell lymphoma.Here,we report a case of follicular lymphoma with cardiac involvement and severe heart failure as the sole clinical manifestation.CASE SUMMARY A 90-year-old male patient was first admitted to our hospital due to an accidentally discovered painless mass in the right lower abdomen.A biopsy of the mass revealed a follicular lymphoma.Positron emission tomography-computed tomography confirmed mild pericardial effusion,and echocardiography showed no structural abnormalities with normal ejection fraction at the time of diagnosis.The patient refused our recommendation of chemotherapy and was re-admitted 4 mo later due to heart failure.A series of subsequent echocardiographic examinations showed thickening of the left ventricular walls and increasing pericardial effusion over the following 2 mo.His heart failure exacerbated despite all symptomatic and supportive treatments.He passed away after an episode of aspiration pneumonia.CONCLUSION The diagnosis of cardiac lymphoma is difficult as its clinical manifestations are nonspecific,and prognosis is poor.

Review of lymphoma in the duodenum: An update of diagnosis and management

The presentation,subtype,and macroscopic images of lymphoma vary depending on the site of the tumor within the gastrointestinal tract.We searched PubMed for publications between January 1,2012 and October 10,2022,and retrieved 130 articles relating to duodenal lymphoma.A further 22 articles were added based on the manual screening of relevant articles,yielding 152 articles for full-text review.The most predominant primary duodenal lymphoma was follicular lymphoma.In this review,we provide an update of the diagnosis and management of representative lymphoma subtypes occurring in the duodenum:Follicular lymphoma,diffuse large B-cell lymphoma,extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue,mantle cell lymphoma,and Tcell lymphomas.

Efficacy and safety of obinutuzumab for the first-line treatment of follicular lymphoma:a subgroup analysis of Chinese patients enrolled in the phase III GALLIUM study

Backgrounds:GALLIUM is a global phase Ⅲ study that demonstrated significant improvements in progression-free survival(PFS)for obinutuzumab plus chemotherapy(G-chemo)vs.rituximab plus chemotherapy(R-chemo)in previously untreated patients with follicular lymphoma(FL).This study aimed to report the results of a subgroup of patients in China.Methods:Patients were randomized to G-chemo or R-chemo.Responders received maintenance therapy for 2 years or until disease progression.The primary endpoint was investigator(INV)-assessed PFS.Secondary endpoints included the overall response rate(ORR)and complete response rate(CRR)at the end of induction chemotherapy,overall survival(OS),and safety.Results:Overall,58 patients with FL were randomized to the G-chemo(n=25)and R-chemo arms(n=33).The INV-assessed PFS rate at 3 years was 81.8%in the G-chemo arm,vs.70.2%in the R-chemo arm(hazard ratio 0.35;95%confidence interval:0.09-1.34;P=0.1120).The INV-assessed CRRs(without positron emission tomography[PET])in these arms were 24.0%and 21.2%,respectively,whereas the ORRs were 80.0%and 90.9%,respectively.INV-assessed CRR-PET was 52.6%in the G-chemo,vs.60.9%in the R-chemo.Median OS was not reached in either arm.Grade 3 to 5 adverse events were more frequent in the R-chemo arm(97.0%vs.88.0%).Conclusions:The results of this subgroup analysis were consistent with those of the global population,and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.Trial registration:ClinicalTrials.gov,No.NCT01332968.

Benefit of rituximab maintenance is associated with Follicular Lymphoma International Prognostic Index in patients with follicular lymphoma

Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.

Clinical significance of the loss of CD20 antigen on tumor cells in patients with relapsed or refractory follicular lymphoma

Aim:Anti-CD20 monoclonal antibody is a cornerstone therapy for follicular lymphoma.Following anti-CD20 therapy,a potential decrease in CD20 antigen,and therefore a loss of the tumor target might be expected.However,the incidence and clinical significance of CD20 loss on tumor cells in patients with relapsed or refractory follicular lymphoma are unknown.This study aims to investigate the incidence and outcome of patients with relapsed or refractory follicular lymphoma patients harboring the loss of the tumor target,CD20.Methods:All consecutive adult patients with relapsed or refractory follicular lymphoma referred to the Early Drug Department at Gustave Roussy were included.The main objectives were to assess the incidence and prognosis of the loss in expression of CD20 antigen on the surface of tumor cells on patient outcome.Results:Over the study period 2013-2018,131 patients were screened for clinical trials with B-cell malignancies in the early drug department of Gustave Roussy in France.Forty-four patients presented with relapsed or refractory follicular lymphoma and 32 had tumor biopsies at the time of relapse that were retained for analysis.The median(range)age was 67.5 years(55.3-75.3)and the median number of prior anti-cancer systemic therapies was 3(2-4).At the time of relapse,CD20 expression was positive in 84%of tumors(n=27)and negative in 16%of tumors(n=5).At a median follow-up of 18.3(0.6-83.3)months,CD20 negativity was associated with a poorer prognosis with a median overall survival of 8.9 months(95%CI:2.4-19.1)in comparison to CD20 positive patients(28.3 months,95%CI:25.1-75.3 months,P=0.019).Conclusion:The loss of the tumor target antigen,CD20,occurred in 16%of patients with relapse or refractory follicular lymphoma.Due to confounding factors in patients who received anti-CD20 immunotherapy,it was not possible to formally establish the prognostic significance of CD20 negativity.However,we suggest that a check for CD20 antigen positivity nevertheless be performed to adapt subsequent therapies for patients with relapsed or refractory follicular lymphoma.

Follicular lymphoma:the diminishing role of chemotherapy

Follicular lymphoma(FL)is the most common indolent non-Hodgkin lymphoma,accounting for 70%of cases in Western countries.Despite this unique name,FL is an extremely heterogeneous disease,both clinically and biologically.The basis of FL heterogeneity lies in the different biological pathways which can be activated,because of the variety of gene mutations that can occur.Today,there is a growing interest in the knowledge of these activated pathways,which is also testified by the presence of a new model that incorporates FL mutations to define patient’s prognosis(m7-FLIPI).These evaluations are also appealing because of the recent possibility of using“targeted therapies”.Targeted therapies are new tools,currently applicable in the setting of relapse/refractory(R/R)disease,where we can find a great variety of“chemo-free”combinations.As in other hematologic malignancies,“cellular therapy”enriches FL drug scenario,including T-cell dependent bispecific antibodies and chimeric antigen receptor(CAR)T-cell.Since FL heterogeneity is the basis of the difference in therapeutic efficacy and disease course among patients,the hope for the future is to understand FL biology more deeply,to better comprehend how to obtain more representative samples and pre-treatment prognostic information in order to individualize the treatment strategy as early as frontline therapy.