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3.
Acta Oncol ; 63: 267-272, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709114

ABSTRACT

BACKGROUND: The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. PATIENTS AND METHODS: We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1-2 FL between 1997 and 2016 in nine institutions were included. RESULTS: The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7-9.3 years), 4.2 years (95% CI: 2.8-5.6 years) and 2.2 years (95% CI 1.7-2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. INTERPRETATION: With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Follicular , Progression-Free Survival , Humans , Lymphoma, Follicular/mortality , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/therapy , Female , Middle Aged , Male , Aged , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged, 80 and over , Rituximab/therapeutic use , Retrospective Studies , Young Adult , Prognosis
4.
J Med Econ ; 27(1): 766-776, 2024.
Article in English | MEDLINE | ID: mdl-38712895

ABSTRACT

AIMS: Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective. MATERIALS AND METHODS: A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len. LIMITATIONS: Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties. CONCLUSION: Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.


Subject(s)
Antibodies, Monoclonal, Humanized , Cost-Benefit Analysis , Lymphoma, Follicular , Quality-Adjusted Life Years , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/economics , United States , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/economics , Female , Male , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Middle Aged , Models, Econometric , Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Retrospective Studies , Adult , Aged , Rituximab/therapeutic use , Rituximab/economics , Cost-Effectiveness Analysis
5.
Expert Opin Biol Ther ; 24(5): 321-326, 2024 May.
Article in English | MEDLINE | ID: mdl-38717336

ABSTRACT

INTRODUCTION: At the 65th American Society of Hematology (ASH) 2023 Annual Meeting, the latest advancements in CD20×CD3 BsAbs for B-cell lymphoma (BCL) were highlighted, particularly in relapsed/refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL). AREAS COVERED: This summary highlights some of the major studies on CD20×CD3 BsAbs for BCL. EXPERT OPINION/COMMENTARY: CD20×CD3 is the most widely studied BsAb, with promising results in patients with R/R DLBCL and R/R FL ≥ two prior lines of systemic therapy. Trials with the first line of B-cell lymphoma also revealed promising results. Hopefully, BsAb monotherapy or BsAb-containing regimens may become the standard therapy in patients with FL and DLBCL.


Subject(s)
Antibodies, Bispecific , Antigens, CD20 , CD3 Complex , Immunotherapy , Lymphoma, Large B-Cell, Diffuse , Adult , Humans , Antibodies, Bispecific/therapeutic use , Antigens, CD20/immunology , Antineoplastic Agents, Immunological/therapeutic use , CD3 Complex/immunology , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/therapy , Lymphoma, Follicular/immunology , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Congresses as Topic
6.
Arch Dermatol Res ; 316(5): 199, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775835

ABSTRACT

BACKGROUND: Following the initial diagnosis of a marginal zone or follicle center lymphoma on skin biopsy, patients undergo staging to determine the extent of disease. OBJECTIVE: We sought to characterize the frequency that these patients were found to have a systemic nodal disease upon work-up as well as the impact of imaging on disease management. METHODS: We conducted a retrospective chart review of patients presenting with a working diagnosis of PCMZL or PCFCL treated at The Ohio State University from 1990 to 2022. Data collected included: patient history, progress notes, virtual encounters, laboratory results, presentation features, imaging, and pathology. Biomarkers included ANA, SSA/SSB, BCL6 and H. Pylori labs, bone marrow biopsies, positive imaging, and need of systemic medication and mortality. RESULTS: 71 patients with suspected PCMZL and PCFCL were identified. 66 of 71 patients underwent imaging. Of this group, 12 patients (9 with suspected PCFCL and 3 with suspected PCMZL) demonstrated lymphadenopathy on imaging. Of these 12 patients, 5 underwent biopsy of suspected lymph nodes, and 3 had biopsy-proven nodal involvement and received systemic therapy. Of the remaining 7 patients with evidence of lymphadenopathy on imaging, 4 were thought to have reactive lymph nodes, and 3 were treated empirically with systemic chemotherapy due to the extent or progression of their disease. Of patients with imaging negative for lymphadenopathy, 3 of 52 (5.8%) patients with received systemic treatment, while 49 of 52 patients (94.2%) received localized treatment. LIMITATIONS: Most of the relationships between this data were correlational and patients selected for this study were limited to a single institution. CONCLUSION: Prospective study of the role of imaging without subsequent lymph biopsy to direct treatment decisions is warranted.


Subject(s)
Lymphadenopathy , Skin Neoplasms , Humans , Male , Retrospective Studies , Female , Middle Aged , Lymphadenopathy/diagnosis , Lymphadenopathy/pathology , Aged , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Skin Neoplasms/pathology , Biopsy , Adult , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/therapy , Lymphoma, B-Cell, Marginal Zone/pathology , Lymph Nodes/pathology , Skin/pathology , Aged, 80 and over , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/pathology , Lymphoma, Follicular/therapy , Lymphoma, Follicular/drug therapy , Neoplasm Staging
7.
Lancet Haematol ; 11(6): e406-e414, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38796193

ABSTRACT

BACKGROUND: Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL. METHODS: Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375). FINDINGS: 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown). INTERPRETATION: Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial. FUNDING: Bristol-Myers Squibb. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.


Subject(s)
Azacitidine , Humans , Male , Female , Aged , Middle Aged , Azacitidine/therapeutic use , Azacitidine/adverse effects , Azacitidine/administration & dosage , Administration, Oral , Bendamustine Hydrochloride/therapeutic use , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/adverse effects , Gemcitabine , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/mortality , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Depsipeptides/therapeutic use , Depsipeptides/adverse effects , Depsipeptides/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/administration & dosage , Aged, 80 and over
8.
Signal Transduct Target Ther ; 9(1): 99, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38627366

ABSTRACT

This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.


Subject(s)
Lymphoma, Follicular , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/genetics , Progression-Free Survival , Phosphoinositide-3 Kinase Inhibitors/therapeutic use
9.
Cancer Med ; 13(8): e7120, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38629251

ABSTRACT

BACKGROUND: Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. RESULTS: Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. CONCLUSION: The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Follicular , Lymphoma, Large B-Cell, Diffuse , Humans , Rituximab/therapeutic use , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/epidemiology , Retrospective Studies , Transplantation, Autologous , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/epidemiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects
10.
Br J Haematol ; 204(5): 1582-1584, 2024 May.
Article in English | MEDLINE | ID: mdl-38581289

ABSTRACT

The role of Pi3K inhibitors in lymphoma is diminishing due to the adverse results from trials in indolent lymphoma, but is a one-size-fits-all approach to drug development penalising some lymphoma subtypes and the newer generation of Pi3K inhibitors? The report by Soumerai et al. of zandelisib with zanubrutinib in follicular and mantle cell lymphoma is an important addition to the data. Commentary on: Soumerai et al. Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas. Br J Haematol 2024;204:1762-1770.


Subject(s)
Phosphoinositide-3 Kinase Inhibitors , Humans , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Lymphoma, Mantle-Cell/drug therapy , Lymphoma/drug therapy , Lymphoma, Follicular/drug therapy , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Piperidines
11.
Zhonghua Xue Ye Xue Za Zhi ; 45(1): 94-97, 2024 Jan 14.
Article in Chinese | MEDLINE | ID: mdl-38527846

ABSTRACT

To investigate the clinical and pathological characteristics of duodenal-type follicular lymphoma (D-FL), and to deepen the understanding of Duodenal-type follicular lymphoma. The clinical symptoms, endoscopic features, pathologic features, immunophenotype, molecular pathological features and treatment follow-up of 18 D-FL patients diagnosed in Department of Pathology, Beijing Tiantan Hospital affiliated to Capital Medical University between January 2020 and July 2023 were summarized. A total of 18 patients with D-FL were included, including 10 males and 8 females. The median age was 49 (32-69) years respectively. Most of the patients were found during gastroenteroscopy or presented with the common gastrointestinal symptoms of stomach pain, acid reflux, vomiting and diarrhea. Most endoscopic findings were multiple small gray and white polyposis. In the pathological morphology, the mucous layer and submucous layer showed lymphoid follicular structures with full and strained follicles. The immunophenotype showed that the tumor cells strongly expressed CD20 and BCL2 and had low proliferation activity. Immunoglobulin clonal analysis of 1 case showed IgK monoclonal rearrangement (1/1). FISH showed 1 case of BCL2 gene rearrangement (1/3). All patients did not receive targeted chemotherapy and adopted a wait-and-see strategy. Median follow-up was 12 (2-34) months. This study shows that D-FL is an indolent lymphoma, which tends to occur in the duodenum and has a good prognosis.


Subject(s)
Lymphoma, Follicular , Male , Female , Humans , Middle Aged , Lymphoma, Follicular/drug therapy , Proto-Oncogene Proteins c-bcl-2
12.
Medicina (Kaunas) ; 60(3)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38541221

ABSTRACT

Background and Objectives: the principal purpose of this literature review is to cluster adults with hematological malignancies after treatment or on maintenance with obinutuzumab who experienced disseminated EV infection to understand clinical characteristics and outcome of this rare condition in these patients. We report the first clinical case of a male affected by follicular lymphoma treated with immune-chemotherapy including obinutuzumab who was affected by disseminated EV infection with cardiovascular involvement. Materials and Methods: this narrative review summarizes all the research about disseminated EV infection in immunosuppressed adult patients treated with obinutuzumab from January 2000 to January 2024 using the Scale for the Assessment of Narrative Review Articles (SANRA) flow-chart. We performed a descriptive statistic using the standard statistical measures for quantitative data. Results: we included six studies, five case reports, and one case report with literature analysis. We collected a total of seven patients, all female, with disseminated EV infection. The most common signs and clinical presentations of EV infection were fever and encephalitis symptoms (N = 6, 85.7%), followed by hepatitis/acute liver failure (N = 5, 71.4%). Conclusions: onco-hematological patients who receive immune-chemotherapy with a combination of treatments which depress adaptative immunity, which includes the antiCD20 obinutuzumab, could be at higher risk of disseminated EV infection, including CNS and cardiac involvement.


Subject(s)
Enterovirus Infections , Lymphoma, Follicular , Adult , Humans , Male , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Enterovirus Infections/complications , Enterovirus Infections/drug therapy , Lymphoma, Follicular/complications , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/pathology
13.
BMC Cancer ; 24(1): 370, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38528445

ABSTRACT

BACKGROUND: Relapsed or refractory follicular lymphoma (rrFL) is an incurable disease associated with shorter remissions and survival after each line of standard therapy. Many promising novel, chemotherapy-free therapies are in development, but few are licensed as their role in current treatment pathways is poorly defined. METHODS: The REFRACT trial is an investigator-initiated, UK National Cancer Research Institute, open-label, multi-centre, randomised phase II platform trial aimed at accelerating clinical development of novel therapies by addressing evidence gaps. The first of the three sequential novel therapy arms is epcoritamab plus lenalidomide, to be compared with investigator choice standard therapy (ICT). Patients aged 18 years or older with biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma and assessable disease by PET-CT are eligible. The primary outcome is complete metabolic response by PET-CT at 24 weeks using the Deauville 5-point scale and Lugano 2014 criteria. Secondary outcomes include overall metabolic response, progression-free survival, overall survival, duration of response, and quality of life assessed by EQ-5D-5 L and FACT-Lym. The trial employs an innovative Bayesian design with a target sample size of 284 patients: 95 in the ICT arm and 189 in the novel therapy arms. DISCUSSION: Whilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05848765; 08-May-2023. EUDRACT: 2022-000677-75; 10-Feb-2022.


Subject(s)
Lymphoma, Follicular , Humans , Lymphoma, Follicular/drug therapy , Positron Emission Tomography Computed Tomography , Arm/pathology , Bayes Theorem , Quality of Life , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic
14.
Leuk Lymphoma ; 65(6): 768-773, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38456694

ABSTRACT

Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Boron Compounds , Glycine , Lenalidomide , Lymphoma, Follicular , Rituximab , Humans , Boron Compounds/therapeutic use , Boron Compounds/administration & dosage , Boron Compounds/adverse effects , Glycine/analogs & derivatives , Glycine/therapeutic use , Glycine/adverse effects , Glycine/administration & dosage , Rituximab/adverse effects , Rituximab/therapeutic use , Rituximab/administration & dosage , Male , Female , Middle Aged , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lenalidomide/administration & dosage , Lenalidomide/therapeutic use , Lenalidomide/adverse effects , Adult , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/mortality , Treatment Outcome , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Aged, 80 and over
15.
Br J Haematol ; 204(5): 1762-1770, 2024 May.
Article in English | MEDLINE | ID: mdl-38500476

ABSTRACT

The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Follicular , Lymphoma, Mantle-Cell , Pyrazoles , Pyrimidines , Humans , Lymphoma, Mantle-Cell/drug therapy , Female , Male , Aged , Middle Aged , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/mortality , Pyrimidines/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Adult , Thiazoles/adverse effects , Thiazoles/administration & dosage , Thiazoles/therapeutic use , Aged, 80 and over , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Treatment Outcome , Piperidines
16.
Int J Hematol ; 119(6): 677-685, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38519820

ABSTRACT

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bendamustine Hydrochloride , Disease Progression , Fluorodeoxyglucose F18 , Lymphoma, Follicular , Positron-Emission Tomography , Rituximab , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/diagnostic imaging , Lymphoma, Follicular/mortality , Bendamustine Hydrochloride/administration & dosage , Rituximab/administration & dosage , Fluorodeoxyglucose F18/administration & dosage , Middle Aged , Aged , Male , Female , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , Japan , Positron-Emission Tomography/methods , Recurrence , Aged, 80 and over , Radiopharmaceuticals/administration & dosage
17.
Pharmacoeconomics ; 42(5): 569-582, 2024 May.
Article in English | MEDLINE | ID: mdl-38300452

ABSTRACT

OBJECTIVE: This study aimed to assess the budget impact of introducing fixed-duration mosunetuzumab as a treatment option for adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies and to estimate the total cumulative costs per patient in the USA. METHODS: A 3-year budget impact model was developed for a hypothetical 1-million-member cohort enrolled in a mixed commercial/Medicare health plan. Comparators were: axicabtagene ciloleucel, tisagenlecleucel, tazemetostat, rituximab plus lenalidomide, copanlisib, and older therapies (rituximab or obinutuzumab ± chemotherapy). Costs per patient comprised treatment-associated costs including the drug, its administration, adverse events, and routine care. Dosing and safety data were ascertained from respective package inserts and clinical trial data. Drug costs (March 2023) were estimated based on the average wholesale acquisition cost reported in AnalySource®, and all other costs were based on published sources and inflated to 2022 US dollars. Market shares were obtained from Genentech internal projections and expert opinion. Budget impact outcomes were presented on a per-member per-month basis. RESULTS: Compared with a scenario without mosunetuzumab, its introduction over 3 years resulted in a budget increase of $69,812 (1% increase) and an average per-member per-month budget impact of $0.0019. Among the newer therapies, mosunetuzumab had the second-lowest cumulative per patient cost (mosunetuzumab = $202,039; axicabtagene ciloleucel = $505,845; tisagenlecleucel = $476,293; rituximab plus lenalidomide = $263,520; tazemetostat = $250,665; copanlisib = $127,293) and drug costs, and its introduction only increased total drug costs by 0.1%. By year 3, the cumulative difference in the per patient cost with mosunetuzumab was -$303,805 versus axicabtagene ciloleucel, -$274,254 versus tisagenlecleucel, -$61,481 versus rituximab plus lenalidomide, -$48,625 versus tazemetostat, and $74,747 versus copanlisib. Older therapies were less costly with 3-year cumulative costs that ranged from $36,512 to $147,885. CONCLUSIONS: Over 3 years, the estimated cumulative per patient cost of mosunetuzumab is lower than most available newer therapies, resulting in a small increase in the budget after its formulary adoption for the treatment of relapsed or refractory follicular lymphoma.


Subject(s)
Antibodies, Monoclonal, Humanized , Budgets , Lymphoma, Follicular , Models, Economic , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/economics , United States , Antibodies, Monoclonal, Humanized/economics , Antibodies, Monoclonal, Humanized/therapeutic use , Cost-Benefit Analysis , Drug Costs , Antineoplastic Agents/economics , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Medicare/economics
18.
Clin Lymphoma Myeloma Leuk ; 24(5): e191-e195.e6, 2024 May.
Article in English | MEDLINE | ID: mdl-38365528

ABSTRACT

In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory follicular lymphoma patients. SCHOLAR-5 is an external control cohort designed to act as a comparator to ZUMA-5. Here, we present an updated comparative analysis of ZUMA-5 and SCHOLAR-5, using the 36-month follow-up data and the intent-to-treat population of ZUMA-5. Using propensity-score methods, 127 patients in ZUMA-5 were compared to 129 patients in SCHOLAR-5. At this extended follow-up, axi-cel continues to demonstrate clinically meaningful benefits in survival compared to historically available treatments in this population.


Subject(s)
Biological Products , Lymphoma, Follicular , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/mortality , Male , Follow-Up Studies , Female , Biological Products/therapeutic use , Biological Products/pharmacology , Middle Aged , Immunotherapy, Adoptive/methods , Aged , Adult , Antigens, CD19/therapeutic use , Antigens, CD19/immunology , Treatment Outcome , Neoplasm Recurrence, Local/drug therapy
19.
Clin Nucl Med ; 49(5): e219-e221, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38409762

ABSTRACT

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.


Subject(s)
Epstein-Barr Virus Infections , Lymphoma, Follicular , Smooth Muscle Tumor , Female , Humans , Aged , Herpesvirus 4, Human , Smooth Muscle Tumor/diagnostic imaging , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnostic imaging , Positron Emission Tomography Computed Tomography , Lymphoma, Follicular/diagnostic imaging , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/complications
20.
Indian J Pathol Microbiol ; 67(2): 411-414, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38391382

ABSTRACT

ABSTRACT: Plasmablastic transformation of follicular lymphoma is very rare and has been reported in only 5 cases till date. We report a case of simultaneous identification of extranodal, soft tissue plasmablastic lymphoma in the ankle and bone marrow involvement by follicular lymphoma. This unusual case presentation is a challenge for the treating physician with the patient becoming resistant to chemotherapy and succumbing to the disease within a few months of diagnosis. These cases are known to have an aggressive clinical course with very poor prognosis and survival rate of less than 6 months. This report broadens the spectrum of morphological transformation of follicular lymphoma and it may represent a new category of high-grade transformation of follicular lymphoma.


Subject(s)
Lymphoma, Follicular , Plasmablastic Lymphoma , Humans , Lymphoma, Follicular/pathology , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/drug therapy , Plasmablastic Lymphoma/pathology , Plasmablastic Lymphoma/diagnosis , Plasmablastic Lymphoma/drug therapy , Bone Marrow/pathology , Male , Fatal Outcome , Middle Aged , Immunohistochemistry , Cell Transformation, Neoplastic/pathology
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