Potential Impact of Pathologic Review on Therapy in Non-Hodgkin’s Lymphoma (NHL): Analysis from the National Comprehensive Cancer Network (NCCN) NHL Outcomes Project.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2816-2816
Author(s):  
Ann LaCasce ◽  
Joyce Niland ◽  
Michelle E. Kho ◽  
Anna terVeer ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
B Cell ◽  
Final Diagnosis ◽  
Routine Care ◽  
Outcome Data ◽  
Pathologic Diagnosis ◽  
First Line Therapy ◽  
Treatment Category ◽  
Potential Impact ◽  
Grade 3 ◽  
Md Anderson

Abstract Background: Optimal therapy of NHL is critically dependent upon an accurate pathologic diagnosis. High inter-rater reliability has been demonstrated among expert hematopathologists for common B cell NHLs using the WHO classification system. However, less is known about the accuracy and reliability of pathologic diagnosis of lymphoma in the routine care setting. Methods: We used data from the NCCN NHL Outcomes Project, a prospective cohort study collecting comprehensive clinical, treatment, and outcome data for patients seen at 5 participating centers (City of Hope, Dana-Farber, Fox Chase, MD Anderson, and Roswell Park), to compare pathologic diagnosis assigned at referring and NCCN centers. Newly diagnosed patients presenting between 7/00 and 12/04 with a final diagnosis of one of the following NHL subtypes were included in this analysis: follicular lymphoma (FL, grades 1,2,NOS), FL grade 3, marginal zone (MZL, extranodal, nodal, and splenic), small lymphocytic (SLL), diffuse large B-cell (DLBCL) and mantle cell (MCL). Diagnosis was considered concordant if the NCCN institution assigned the same WHO diagnosis as the referring institution. In order to assess the potential impact of diagnostic reclassification on treatment and outcomes, we defined 6 outside institution treatment-oriented categories: Indolent 1 (FL 1,2,NOS, all types of MZL and SLL), Indolent 2 (FL 3), Aggressive (i.e. DLBCL), MCL, Highly Aggressive (e.g. Burkitt or lymphoblastic lymphoma) and Other Cancer. NCCN diagnoses were classified into 4 treatment-oriented categories: Indolent 1, Indolent 2, DLBCL, and MCL. Treatment category was considered concordant if the diagnosis assigned by the referring institution and the NCCN institution mapped to the same treatment category. Results: Of 928 patients eligible for this analysis, 741 had specimens reviewed at both a referring and NCCN institution. Among these patients, the final diagnosis was discordant for 9% (66/741, 95%CI [7%,11%]). The rates of discordance by histologic type (as assigned by the NCCN center) were: FL 6% (13/218), FL3 16%(5/31), MZL 8% (5/60), SLL 29% (9/31), DLBCL 8% (25/304) and MCL 9% (9/97). In SLL, almost half of discordance was due to use of non-WHO diagnoses (n=4). Of the 66 discordant cases, 51 (7% of total, 95% CI [5%, 9%]) were ultimately diagnosed with a histology that mapped to a discordant treatment category. This included 15 patients (29%) whose final diagnosis was a more aggressive histology (DLBCL), potentially curable if treated with appropriate first-line therapy. Conclusions: We found that the vast majority of patients with common NHL were classified accurately by referring centers. For 9% of patients, however, review by an expert hematopathologist resulted in an alternative diagnosis, and for the majority a change in expected treatment potentially impacting therapeutic outcome. Treatment Category NCCN Referring Institution Indolent 1 (N=309) Indolent 2 (N=31) DLBCL (N=304) MCL (N=97) Indolent 1 94% 10% 4% 7% Indolent 2 1% 84% 1% 0 Aggressive 1% 6% 93% 1% MCL 2% 0 0 91% Highly Aggressive 1% 0 1% 1% Other Cancer 1% 0 <1% 0

CPOP-R Versus CHOP-R As First-Line Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): A Phase 2, Randomized, Open-Label, Multicenter Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1605-1605
Author(s):  
Raoul Herbrecht ◽  
David MacDonald ◽  
Florian Weissinger ◽  
Martin Wilhelm ◽  
Charles Holladay ◽  
...  
Keyword(s):  
B Cell ◽  
Troponin T ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Comparable Efficacy ◽  
High Survival ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

Abstract Abstract 1605 Introduction: CHOP-R is standard therapy for patients with untreated DLBCL. Pixantrone dimaleate (P) is a novel aza-anthracenedione that, unlike doxorubicin (D), forms stable DNA adducts and has enhanced efficacy compared to D in preclinical lymphoma models. Due to its inability to bind iron or form alcohol metabolites, P has substantially less cardiotoxicity than D or mitoxantrone in preclinical studies. In a Phase I-II study in 65 patients with relapsed aggressive B cell NHL after CHOP (±R), patients treated with CPOP (P replaced D in CHOP) had CR/CRu rate of 52% and an overall response rate (ORR) of 77% with median progression-free survival (PFS) of 8.2 months and overall survival (OS) of 17.9 months (Leuk Lymph 2011;52: 620–8). The present Phase II study evaluated efficacy and safety, particularly cardiotoxicity, of CPOP-R vs CHOP-R as first-line therapy in patients with DLBCL. Patients and Methods: Patients with untreated DLBCL (CD20+, stage II-IV disease) were randomized to CPOP-R or CHOP-R (1: 1). CHOP-R was administered at standard doses; in CPOP-R, P (150 mg/m2) was substituted for D. After 4 cycles, patients with a partial response (PR) received 4 more cycles of treatment; those with CR received 2 more cycles. Follow-up after treatment was 36 months. Response was assessed by an independent assessment panel. A primary objective to evaluate non-inferiority of CPOP-R to CHOP-R, measured by CR/CRu rates, required 280 patients. Secondary endpoints included ORR, PFS, OS, and time to progression (TTP) and safety. Enrollment was stopped after 124 patients because of resource constraints; the study was no longer powered to detect non-inferiority. Results: Of the 124 patients enrolled, 61 were randomized to CPOP-R and 63 to CHOP-R. Treatments were administered to 122 patients (98%). Demographics and baseline disease characteristics were balanced between arms. Median age was 68 years in both arms, 79% of patients in CPOP-R vs 78% in CHOP-R were Ann Arbor stage 3–4, 48% vs 54% had IPI ≥3, and 20% vs 11% had ≥3 comorbid conditions. Median number of cycles delivered was 8 for CPOP-R vs 6 for CHOP-R. CR/CRu rate in the ITT population was 72.1% for CPOP-R vs 79.4% for CHOP-R (95% CI for the difference = −7.8%, 22.3%) and ORR (CR+CRu+PR) was 82.0% vs 87.3%. PFS appeared similar for CPOP-R and CHOP-R (HR=1.08). TTP was also similar (median not reached in either arm). Median OS was not reached in either arm (HR=2.34, 95% CI=1.05, 5.22, P =.032). The 3-year survival rates were 66% in CPOP-R vs 85% in CHOP-R. Three-year survival for patients with IPI ≤2 was 82% for CPOP-R vs 86% for CHOP-R; IPI ≥3, survival was 50% vs 84%. It was unusual that in the CHOP-R arm, patients with the modal IPI score=3 (n=25) had a better survival than patients with IPI ≤2 with only 8% mortality at 3 years. This historically high survival rate for CHOP-R patients with IPI=3 appeared responsible for the disparate survival rates between CPOP-R and CHOP-R. Eight patients in CPOP-R and 2 in CHOP-R had a history of coronary artery disease, congestive heart failure (CHF), or myocardial infarction. Overall, adverse events (AEs) were similar between arms; grade 3/4 AEs occurred in about 85% of patients in both arms. Incidence of grade 3/4 AEs was similar for neutropenia (61.0% vs 60.3%), febrile neutropenia (15.3% vs 15.9%), thrombocytopenia (5.1% vs 6.3%), and infections (16.9% vs 17.5%). Stomatitis was less common in CPOP-R (6.8% vs 17.5%). LVEF was measured prospectively at intervals through 24 months. LVEF values were generally stable in CPOP-R, but declined significantly from baseline in CHOP-R (P <.05). One patient in CPOP-R vs 8 in CHOP-R had LVEF declines ≥20% (P<.05). In CPOP-R, 6.7% of patients vs 35.2% in CHOP-R developed elevated troponin T levels (P<.05). No patients in CPOP-R vs 4 in CHOP-R developed CHF. Three deaths occurred within 30 days of last dose in CPOP-R vs none in CHOP-R. Most deaths after treatment in both arms were related to progressive disease. Conclusions: This study compared CPOP-R, a pixantrone-containing regimen, with CHOP-R as first-line therapy for DLBCL and showed comparable efficacy as measured by response, PFS, and TTP. Hematopoietic toxicities were similar; however, CPOP-R had reduced cardiotoxicity as determined by overall and serious declines in LVEF, elevations in troponin T, and CHF occurrence. Non-inferiority of CPOP-R to CHOP-R could not be established. Disclosures: Herbrecht: Cell Therapeutics, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cernohous:Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment. van der Jagt:Cell Therapeutics, Inc: Consultancy, Research Funding.

Pharmacokinetics and efficacy of pegfilgrastim as hematopoietic support for dose-dense every-2-week chemo-immunotherapy with R-CHOP as first-line therapy in elderly patients with diffuse large B cell lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17531-17531 ◽  
Author(s):  
U. J. Mey ◽  
A. Maier ◽  
R. Kleinschmidt ◽  
C. Ziske ◽  
H. Forstbauer ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Fixed Dose ◽  
Neutrophil Recovery ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

17531 Background: Recently, 6 cycles of R-CHOP-14 have been recommended as reference standard for elderly patients with diffuse large B cell lymphoma (Pfreundschuh, 2004). Pegfilgrastim as a pegylated form of G-CSF has been shown to provide rapid neutrophil recovery and facilitate dose dense chemotherapy schedules with a single administration per chemotherapy cycle. The aim of this study was to analyze pharmacokinetics of a single fixed dose of 6 mg of pegfilgrastim per cycle in a homogenous group of elderly patients with diffuse large B cell lymphoma treated with R-CHOP as first-line therapy in two-weekly intervals. Methods: Ten patients with diffuse large B cell lymphoma between the age of 60 and 80 years received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after the administration of R-CHOP chemo-immunotherapy, repeated for 6 to 8 cycles in two-weekly intervals. Pegfilgrastim plasma levels as well as absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles. Incidence and duration of grade 3/ 4 neutropenia, depth of neutrophil nadir and incidence of febrile neutropenia were assessed. Results: Median age was 73.4 years. A single 6 mg injection of pegfilgrastim 24 h after the administration of CHOP was effective to allow neutrophil recovery in 69 of 70 (98.6%) two-weekly treatment cycles. Median absolute neutrophil nadir was 0.38 G/l on day 9. Grade 3/ 4 granulocytopenia occurred in all ten patients. Mean duration of grade 3/4 neutropenia (< 1.0 G/l) was two days. Febrile neutropenia occurred in one patient. Plasma levels of pegfilgrastim remained elevated during the neutropenic phase. At the start of hematologic recovery, plasma concentrations of pegfilgrastim decreased rapidly as a result of clearance by the neutrophils. Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application. Conclusions: A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to safely allow two-weekly drug administration in previously untreated elderly patients with diffuse large B cell lymphoma. [Table: see text]

Niespecyficzny obraz chłoniaka B-komórkowego u dwuipółletniej dziewczynki – opis przypadku

2019 ◽  
Vol 24 (3) ◽  
Author(s):  
Ewa Krasuska-Sławińska ◽  
Izabela Królik-Elgas ◽  
Marzena Stypińska ◽  
Anna Matosek-Rutkowska
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Histopathological Examination ◽  
B Cell Lymphoma ◽  
Final Diagnosis ◽  
Lymphoblastic Lymphoma ◽  
Final Conclusion ◽  
Dental Surgery ◽  
Non Hodgkin Lymphoma ◽  
Primary Location

B-cell lymphoblastic lymphoma which is a type of non-Hodgkin lymphoma is rather uncommon in children. Focal changes in bones in the course of non-Hodgkin lymphoma are mostly secondary changes and their primal location in a bone is rare. PBL (primary bone lymphoma) mainly concerns a thighbone and a tibial bone; the primary location in jaw bones is quite sporadic. In diagnostics, there is mainly magnetic resonance, medical scan (tomography), and above all – histopathological test. There is also chemotherapy by choice, and primary location in a jaw or a mandible significantly advances the prognosis. The aim of the work is to introduce a patient who was definitively diagnosed B-cell lymphoblastic lymphoma from the early B-cells. The girl reported to Laryngological Clinic, Dental Surgery Clinic for Children, Oncological Clinic of Children’s Memorial Health Institute. The cause of the visit was an elevation on the right side of a nose base, present for two months and misdiagnosed by doctors as a post-traumatic swelling in this region. After introducing laboratory and scan diagnostics and taking biopsy from the lesion, a final conclusion was made. Also, a proper treatment according to the protocol for B-cell lymphoblastic lymphoma was introduced. Non-specific B-cell lymphoma picture, as mentioned in the described case, specifically due to location in a jaw bone and a slow pace of growing, may both constitute huge diagnostic problems and deteriorate prognosis. Therefore, it is important to take into account also lymphoma – in such location of a lesion. Moreover, it is worth remembering that the final diagnosis may only be passed on the basis of histopathological examination.

scholarly journals Chronic Myeloid Leukemia in India

2017 ◽  
Vol 3 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Prasanth Ganesan ◽  
Lalit Kumar
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Population Based ◽  
Outcome Data ◽  
Published Data ◽  
Molecular Monitoring ◽  
Quality Of Data ◽  
Assistance Programs ◽  
First Line Therapy ◽  
Line Therapy

Background In the last decade, the use of imatinib has brought a paradigm shift in the management of chronic myeloid leukemia (CML). In India, imatinib has been available for more than a decade and has been made accessible to all segments of the population because of patient assistance programs and cheaper generic versions. Despite improvements in survival, there are unique challenges in the Indian context. Methods We reviewed published data pertaining to CML in India for the period of 1990 to 2016, using PubMed advanced search with the terms chronic myeloid leukemia and India, and included studies that reported on epidemiology, monitoring for therapy, treatment outcomes, and resistance. Additionally, the references in retrieved articles were also reviewed. Results Thirty-seven studies were identified. The incidence of CML may be slightly lower in India than in the West, but there was only a single article reporting population-based data. Indian patients presented with more advanced disease. Most centers have access to imatinib as first-line therapy, but there is limited availability of molecular monitoring and second-line therapy. Most of the outcome data were retrospective but seemed comparable with that reported in Western centers. Drug adherence was impaired in at least one third of patients and contributed to poor survival. Conclusion Focused prospective studies and cooperative studies might improve the quality of data available. Future studies should focus on adherence, its effects on outcomes, and methods to address this problem.

scholarly journals Ixazomib in Previously Untreated Indolent B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5326-5326
Author(s):  
Solomon A. Graf ◽  
Ryan C. Lynch ◽  
David G. Coffey ◽  
Mazyar Shadman ◽  
Sandra Kanan ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Response Assessment ◽  
Clinical Indication ◽  
Non Hodgkin Lymphoma ◽  
Tumor Reduction ◽  
Frontline Treatment ◽  
Grade 3 ◽  
Indication For Treatment

Abstract Background: Frontline treatment of indolent B-cell non-Hodgkin lymphoma (iB-NHL) typically involves intravenously administered anti-CD20 monoclonal antibodies with or without cytotoxic chemotherapy. Effective and low-toxicity therapies with improved convenience of administration are sought. We hypothesized that ixazomib (Ix) could safely and conveniently induce remissions in patients with untreated iB-NHL. Here we present the first data on frontline use of Ix in untreated iB-NHL. Methods: This single-arm, open-label phase II "window" trial for patients with untreated iB-NHL (NCT02339922) opened to enrollment in May 2016. Eligibility included histopathologically confirmed iB-NHL, measurable disease, a clinical indication for treatment based on NCCN guidelines, and no prior systemic treatment. Ix was administered at 4 mg orally once a week on consecutive 28-day cycles until disease progression or unacceptable toxicity and four doses of weekly rituximab (R) were added during the 7th cycle, after the initial window period. The primary endpoint was investigator-assessed response rate after independent radiology review. Response assessment occurred at every 2 cycles and using standard (Lugano) criteria. Tumor tissue was collected for gene expression profiling and immunohistochemical evaluation of molecular pathways associated with proteasome inhibition. Results: As of July 1, 2018, 15 patients were treated. The median age was 64 years (range, 47 to 81) and 53% were men. Disease histologies included follicular lymphoma (FL, n = 10), mantle cell lymphoma (MCL, n = 2), marginal zone lymphoma (MZL, n = 2), and small lymphocytic lymphoma (SLL, n = 1). At the start of therapy, all had stage III/IV disease and B-symptoms were present in 40%. For patients with FL, 80% had poor risk by FLIPI. Overall, the indication for treatment included symptoms due to disease (40%), steady progression of disease (33%), and cytopenia due to disease (27%). To date, 14 patients were evaluable for response and 13 experienced tumor burden reduction during the Ix-only window (Figure 1). Of patients with FL, 6 completed the Ix-only window phase and, of these, 5 achieved PR. An additional 4 patients with FL have not completed all 6 cycles of Ix monotherapy. Of these, 1 patient achieved a PR after 4 cycles and continues on treatment, 1 patient came off study with stable disease after 4 cycles, and 2 patients have experienced tumor reduction without meeting formal response criteria and continue on treatment (after 2 and 4 cycles, respectively). Of those patients with FL that received R, all achieved formal remission (3 CR, 3 PR). Median progression free survival has not been reached with a median follow up of 7.4 months. No patient with non-FL histology had yet achieved a PR during the Ix-only window or had undergone response assessment after receiving R at the time of the data cut. The most common adverse events (AEs) for all pts were grade 1-2 and included nausea (53%), diarrhea (53%), rash (40%), and fatigue (33%). Peripheral neuropathy occurred in 20% patients (grade 2 in 7%). A single grade ≥ 3 AE occurred (syncope, grade 3). Conclusions: Data from this interim analysis suggest that Ix monotherapy is well tolerated and highly active in the frontline treatment of FL with all patients demonstrating tumor reduction to date and augmented responses following the addition of R. Non-FL histologies of B-NHL appear less responsive to Ix, but numbers are small. Accrual on study continues. Correlative analyses are underway to determine if Ix or Ix-R may represent a viable frontline option for some patients with iB-NHL. Figure 1. Waterfall plot of response. Number of cycles of treatment received to date indicated for each subject. Four weekly doses of rituximab are added, per protocol, with the 7th cycle of ixazomib. Asterisk indicates treatment on study ongoing. Disclosures Graf: Acerta: Research Funding; TG Therapeutics: Research Funding; Beigene: Research Funding. Lynch:T.G. Therapeutics: Research Funding; Takeda Pharmaceuticals: Research Funding; Rhizen Pharmaceuticals S.A.: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Shadman:Genentech: Consultancy; Genentech: Research Funding; Verastem: Consultancy; AbbVie: Consultancy; Gilead Sciences: Research Funding; Beigene: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy; AstraZeneca: Consultancy; TG Therapeutics: Research Funding; Mustang Biopharma: Research Funding; Pharmacyclics: Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding. Gopal:Pfizer: Research Funding; Aptevo: Consultancy; BMS: Research Funding; Brim: Consultancy; Asana: Consultancy; Seattle Genetics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Takeda: Research Funding; Merck: Research Funding; Janssen: Consultancy, Research Funding; Spectrum: Research Funding; Incyte: Consultancy; Teva: Research Funding.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Preliminary results of the phase 2 study of zanubrutinib in patients with previously treated B-cell malignancies intolerant to ibrutinib and/or acalabrutinib.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19506-e19506
Author(s):  
Mazyar Shadman ◽  
Jeff Porter Sharman ◽  
Moshe Y. Levy ◽  
Ryan Porter ◽  
Syed Farhan Zafar ◽  
...  
Keyword(s):  
B Cell ◽  
Kinase Inhibitors ◽  
Median Number ◽  
Additional Treatment ◽  
Lymphocytic Leukemia ◽  
Continuous Treatment ◽  
Duration Of Treatment ◽  
B Cell Malignancies ◽  
Preliminary Results ◽  
Grade 3

e19506 Background: Many patients (pts) with B-cell malignancies require continuous treatment with Bruton tyrosine kinase inhibitors (BTKi). Adverse events (AEs) are a common reason for ibrutinib (ibr) or acalabrutinib (acala) discontinuation. Early data from BGB-3111-215 showed zanubrutinib (zanu) was well tolerated in pts with B-cell malignancies intolerant to ibr or acala. We report preliminary results with a median follow-up of 4.2 mo. Methods: Pts meeting protocol criteria for intolerance to ibr, acala or both (without documented progressive disease) were given zanu monotherapy (160 mg twice daily or 320 mg once daily). Recurrence of AEs that led to intolerance of prior BTKi and additional safety measures were assessed based on the Common Terminology Criteria for AEs v5.0. Investigators determined responses using disease status at study entry as baseline. Results: As of November 1, 2020 (cutoff), 44 pts (n=34 chronic lymphocytic leukemia/small lymphocytic lymphoma, n=6 Waldenström macroglobulinemia, n=2 mantle cell lymphoma, n=2 marginal zone lymphoma) were enrolled, received ≥1 dose of zanu, and analyzed for safety. Median age was 70.5 y (range, 49-91); median duration of treatment was 4.2 mo (range, 0.1-12.6). Median number of prior regimens was 2 (range, 1-12). Regarding prior BTKi, 39 pts received ibr only, 4 received ibr and acala, and 1 received acala only. The median number of ibr- or acala-intolerant AEs per pt was 2 (range, 1-5). 83% of ibr and 78% of acala intolerant events did not reccur on zanu; Table. At data cutoff, 43 pts remained on treatment; 1 withdrew consent due to zanu-unrelated grade 3 syncope. Overall, 34 pts (77.3%) reported any AE; most commonly reported AEs were myalgia (n=9; 20.5%), contusion (n=8; 18.2%), dizziness (n=7; 15.9%), fatigue (n=7; 15.9%), and cough (n=5; 11.4%). Grade ≥3 AEs were reported in 6 pts (13.6%), serious AEs in 1 pt (2.3%, febrile neutropenia and salmonella infection), AEs requiring dose interruptions in 6 pts (13.6%), and AEs leading to dose reduction in 2 pts (4.5%). No AEs led to zanu discontinuation. No deaths were reported. All efficacy evaluable pts (26/26 [100%]) maintained (10 [38.5%]) or achieved deepening (16 [61.5%]) of their response. Conclusions: Zanu provides an additional treatment option after intolerance to other BTKi, demonstrating tolerability and sustained or improved efficacy. Updated results will be presented. Recurrence and Severity Change of AEs Leading to Ibr or Acala Intolerance. Clinical trial information: NCT04116437. [Table: see text]

Intravascular large B-cell lymphoma presenting with reticular telangiectasia on the trunk and panhypopituitarism: an autopsy case

2021 ◽  
Vol 14 (3) ◽  
pp. e239422
Author(s):  
Midori Tokushima ◽  
Masaki Tago ◽  
Naoko E Katsuki ◽  
Shu-ichi Yamashita
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Histopathological Examination ◽  
B Cell Lymphoma ◽  
Final Diagnosis ◽  
Skin Lesions ◽  
Lower Abdomen ◽  
Large B Cell Lymphoma ◽  
Skin Induration ◽  
Large B Cell

A 75-year-old woman developed redness and swelling on her truncal skin, spreading from the lower abdomen to left thigh, 2 months before being admitted to our hospital. She was urgently hospitalised because of her worsening respiratory condition. On admission, she had reticular telangiectasia, diffuse skin induration on the lower abdomen and panhypopituitarism. She was diagnosed with intravascular large B-cell lymphoma (IVLBCL) by the third random abdominal skin biopsy. After histopathological examination at autopsy, we made a final diagnosis of IVLBCL causing respiratory failure and panhypopituitarism. This is the rare case of IVLBCL-induced panhypopituitarism showing visible skin lesions.

IVAC +/- R for Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas: Real-World Experience in the Modern Era

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Michael J Buege ◽  
Phuong H Dao ◽  
Esther Drill ◽  
Andréa C LeVoir ◽  
Terry Pak ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Advisory Committees ◽  
Prophylactic Measures ◽  
Grade 3

Introduction Part B of the modified Magrath regimen (ifosfamide, etoposide, and cytarabine; IVAC) with or without rituximab (R) is utilized as a standalone regimen in the management of relapsed/refractory Burkitt lymphoma and other non-Hodgkin lymphomas (NHL). There are no comparative or prospective data and a paucity of retrospective, non-comparative data to support use of this regimen. A small retrospective study described second-line IVAC use without R in a mixed cohort of patients with diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma, suggesting utility as a bridge to hematopoietic cell transplantation (HCT) (Pereira J, et al. Leuk Res. 2006 Jun;30(6):681-5). The activity of this regimen in B-cell NHL, particularly in conjunction with R, and its toxicity remain incompletely described. In this study, we describe our institutional experience with IVAC +/- R in relapsed/refractory B-cell NHL. Methods We reviewed all patients with relapsed/refractory B-cell NHL treated with IVAC +/- R between 1 January 2004 and 30 September 2019 at Memorial Sloan Kettering Cancer Center to assess efficacy and toxicity. Patients who received IVAC as part of sequential or alternating chemotherapy were excluded. Standard dosing consisted of ifosfamide 1500mg/m2 IV over 60min days 1-5, etoposide 60mg/m2 IV over 60min days 1-5, cytarabine 2000mg/m2 IV over 3 hours every 12 hours days 1-2, with or without rituximab 375mg/m2 IV day 0 or 1 in 21- to 28-day cycles (Lacasce A, et al. Leuk Lymphoma. 2004 Apr;45(4):761-7). Results Cohort and treatment characteristics are described in Table 1. Among 54 eligible patients (median age 51 years), 76% had DLBCL; 30% had lymphomatous central nervous system involvement at the time of initiating IVAC. Patients had received median 2 prior lines of therapy, with the last dose of the most recent line of therapy administered a median of 3 weeks prior to initiating IVAC. Patients received median 2 cycles of IVAC +/- R; 48% received IVAC-R. Prophylactic antimicrobials with cycle 1 were utilized in 94%. Most patients received herpesvirus- (81%) and Pneumocystis- (80%) directed prophylaxis; broad-spectrum prophylaxis with a fluoroquinolone was less common (24%). Primary granulocyte colony stimulating factor (GCSF) was utilized in 93% of patients with cycle 1; primary or secondary GCSF was utilized in 94% of cycles. Efficacy outcomes are described in Table 1. Objective response rate (ORR) among 46 evaluated patients was 48%; 17% achieved CR. ORR did not vary significantly between patients who did or did not receive R (58% vs 42%; p = 0.5) but was associated with number of IVAC cycles administered (among responders, 69% received 3-4 cycles while 31% received 1-2 cycles; p &lt; 0.001). At median follow-up of 22 months, median progression-free survival (PFS) and overall survival (OS) were 3.1 months and 4.9 months, respectively (Figure). In Cox proportional hazard regression analysis of survival, patients who received R with every cycle (p = 0.025) and received 3 or more cycles (p &lt; 0.001) experienced significantly longer PFS. Patients who achieved CR (p &lt; 0.001) or PR (p = 0.003), received R with every cycle (p &lt; 0.001), received 3 or more cycles (p &lt; 0.001), or underwent subsequent HCT or CAR-T cell therapy (p = 0.001) experienced significantly longer OS. Toxicity outcomes are described in Table 2. Grade ≥ 3 anemia (93%), neutropenia (94%), and thrombocytopenia (100%; all grade 4) were common, regardless of number of cycles received. Febrile neutropenia (FN) occurred in 65% of patients and complicated 47% of cycles; documented infection occurred in 44%. Risk of FN and infection did not appear to be influenced by use of antimicrobial or GCSF prophylaxis. Grade ≥ 3 elevations in AST/ALT or total bilirubin were uncommon (5.6% and 9.3%, respectively). Neurotoxicity attributed to cytarabine or ifosfamide occurred in 17% of patients and was usually low-grade; hemorrhagic cystitis occurred in one patient. In patients for whom cause of death was documented (n = 37), mortality was attributed to a treatment-related complication in 19%. Conclusion IVAC-R may be a useful bridging therapy for patients with relapsed/refractory B-cell NHL who are planned for HCT. However, its potential for profound hematologic toxicity and life-threatening complications despite prophylactic measures requires careful consideration of less toxic alternatives. Disclosures Straus: Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer; Targeted Oncology: Consultancy, Speakers Bureau; Imedex, Inc.: Speakers Bureau; NY Lymphoma Rounds: Consultancy; Takeda Pharmaceuticals: Research Funding, Speakers Bureau; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Speakers Bureau; ASH: Other: Conference in December 2019 on HL to other physicians during ASH; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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