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Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 234-239
Author(s):  
Kristie A. Blum

Abstract Positron emission tomography (PET)–adapted chemotherapy and radiotherapy approaches are currently used for the initial treatment of early-stage Hodgkin lymphoma (HL) with progression-free survival and overall survival exceeding 85% and 95%, respectively. However, despite general agreement on the prognostic value of interim PET in HL, frontline treatment approaches vary among institutions with respect to how pretreatment clinical risk factors determine treatment selection, the definition of PET negativity, which chemotherapy regimen to initiate and how many cycles to administer, and when to incorporate radiation. Furthermore, as recent trials have confirmed improved efficacy and manageable toxicity when brentuximab and checkpoint inhibitors are combined with frontline regimens such as doxorubicin, vinblastine, and dacarbazine in advanced-stage HL, these agents are now under evaluation as frontline therapy in early-stage HL. A number of issues will affect the use of these agents in early-stage HL, including the costs, early and late toxicities with these agents, patient population (favorable or unfavorable risk groups), how to incorporate them (concurrently or sequentially), and whether they can ultimately replace cytotoxic therapy with similar efficacy and fewer late effects. Future treatment paradigms for early-stage HL may change significantly once randomized studies are completed incorporating these agents into frontline therapy. Ideally, frontline use of brentuximab and checkpoint inhibitors in early-stage HL will result in improved outcomes compared with current PET-adapted approaches with decreased risks of late toxicities that continue to afflict long-term survivors of HL.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4548-4548
Author(s):  
Ajay Major ◽  
Emily Symes ◽  
Sonali M. Smith ◽  
Girish Venkataraman

Abstract Background Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma that typically presents with early-stage favorable disease and exhibits an indolent clinical course with long-term remissions and eventual relapse. Histopathologic variants of NLPHL have recently been described and may have poorer outcomes compared to typical NLPHL. Risk of transformation of variant NLPHL has not been previously described. Methods We retrieved patients with NLPHL diagnosed between 2001 and 2016 whose cases had been reviewed at the University of Chicago and who had available clinical information. Patient characteristics, initial histology, treatment history, history of progression and histologically-verified transformation, and survival status were obtained from the electronic medical record. Patients were grouped into three cohorts: NLPHL, variant NLPHL, and transformed NLPHL (t-NLPHL) at diagnosis. t-NLPHL included diffuse large B-cell lymphoma (t-NLPHL/DLBCL) and T-cell/histiocyte-rich large B-cell lymphoma (t-NLPHL/THRBCL) histologies. Standard descriptive statistical analyses were performed. Relapse-free survival (RFS), transformation-free survival (TFS), and overall survival (OS) were estimated by the Kaplan-Meier method. All statistical analyses were performed using STATA, version 15.1. Results There were 48 patients with newly-diagnosed NLPHL: 34 with NLPHL (71%), 8 with variant NLPHL (17%), and 6 with t-NLPHL (13%) at diagnosis. Patient, disease and frontline treatment characteristics are displayed in Table 1. There was no significant difference in age, male predominance, initial disease stage, or presence of extranodal disease between the three cohorts. B symptoms were more likely in t-NLPHL, and patients with t-NLPHL at diagnosis were more likely to receive frontline R-CHOP. Patients with variant NLPHL were significantly more likely to have progressive disease after frontline therapy. A total of 26 patients (54%) developed relapsed disease and 6 (13%) developed subsequent t-NLPHL (Table 2). The majority of histologically-confirmed relapses were NLPHL (N = 12, 71%), and the majority of subsequent transformations were t-NLPHL/THRBCL (N = 4, 66%). Nearly all of the patients with subsequent transformations developed t-NLPHL at the time of first relapse (N = 5, 83%). There was no significant difference in incidence of relapse or histology at relapse, nor was there any difference in incidence of transformation or histology at transformation, between the three cohorts. RFS, TFS and OS for each cohort are displayed in Figure 1, with a median follow-up of 8.5 years (range 1.5-34.5 years). Between the three cohorts, there was no significant difference in RFS (p = 0.46) or OS (p = 0.29). There was a significant difference in TFS between the typical and variant NLPHL cohorts (p = 0.048), although the number of transformation events was low. A total of 6 patients (13%) died, with no significant difference in incidence of death or cause of death between the three cohorts (Table 2). Only 1 patient in the entire cohort died from lymphoma, a patient with variant NLPHL who died of transformed lymphoma. There were three deaths secondary to treatment (myelodysplastic syndrome, acute lymphocytic leukemia, and cardiomyopathy). Conclusions This single-center retrospective study suggests that variant NLPHL was less likely to respond to frontline therapy and had a shorter transformation-free survival compared to typical NLPHL, but without compromise in terms of PFS and OS. This suggests that current salvage therapies are effective for relapsed and transformed variant NLPHL. Investigation of transformation risk in variant NLPHL with larger datasets is warranted. Figure 1 Figure 1. Disclosures Smith: Alexion, AstraZeneca Rare Disease: Other: Study investigator; Celgene, Genetech, AbbVie: Consultancy. Venkataraman: EUSA Pharma: Consultancy.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2342-2342
Author(s):  
Andrew Doan ◽  
Holly K.T. Huang ◽  
Ari J. Hadar ◽  
Jemily Malvar ◽  
Teresa Rushing ◽  
...  

Abstract Children with acute myeloid leukemia (AML) are commonly treated using a daunorubicin-cytarabine ±etoposide (DA/ADE) backbone as developed by the Medical Research Council (MRC) AML 12 trial and since adopted by the Children's Oncology Group (COG). This regimen is an anthracycline-intensive regimen, incorporating mitoxantrone in the consolidation phase, with a stated cumulative cardiotoxic exposure of ~444 mg/m 2 doxorubicin equivalents, though recent data suggests mitoxantrone is more cardiotoxic than previously considered (~10x more cardiotoxic than doxorubicin instead of 3x). The MRC AML15 trial randomized DA/ADE versus fludarabine-cytarabine-idarubicin (FLAG-Ida) and found superior event-free survival (EFS) from FLAG-Ida, with fewer cycles of intensive chemotherapy (4 vs 5), and less than half the cardiotoxic exposure, potentially reducing acute and long-term morbidity. Experience with FLAG-Ida as frontline therapy in children with de novo AML is limited. Following MRC 15, minimal residual disease (MRD) monitoring has become standard of care for risk stratification in AML, but MRD data for the FLAG-Ida regimen in children has not yet been reported. We collected data from 30 pediatric patients (age 0.3-20.0 years) with newly diagnosed de novo AML (no preceding myelodysplastic syndrome, secondary AML, or prior malignancy) and no underlying genetic disease (e.g., Trisomy 21, Fanconi Anemia, Kostmann Syndrome, Shwachman-Diamond Syndrome) treated at our institution with MRC 15-style FLAG-Ida between 2014 and 2021 (Table 1). Each case was characterized by cytogenetics, chromosomal microarray analysis (since 2015, in 29/30), and a proprietary molecular testing panel (since 2017, in 21/30); AML risk category was assigned at diagnosis using the contemporary COG classification (AAML1831). Following Induction I and II, MRD was measured in each patient by multiparameter flow cytometry using a 'difference from normal' approach (MRD+ defined by contemporary COG threshold, MRD≥0.05%). Patients with poor disease response (MRD+) or high-risk cytogenetics proceeded to hematopoietic stem cell transplantation (HSCT) in first remission. Patients routinely received antimicrobial prophylaxis with sulfamethoxazole-trimethoprim, an azole or echinocandin, and levofloxacin. The study was approved by the Institutional Review Board. Following Induction I, 28/30 (93%) patients were MRD negative, and 30/30 (100%) patients following Induction II. Only 1/20 (5%) patients without high-risk AML required HSCT for slow-responding disease; 1/30 (3%) patients were unable to proceed to consolidation (prolonged myelosuppression). No patient developed treatment-related mortality (TRM) during pre-HSCT chemotherapy (2 subsequent to HSCT). Cardiac evaluation in surviving patients was normal (LVSF>28%) post-therapy in 23/24 (96%). Median survival for patients alive at last follow-up was 2.3 years with overall 3-year EFS and overall survival (OS) of 73±9% and 80±8%, respectively (Figure 1A). Survival for patients in the low-risk subset is depicted (Figure 1B, 1C); all low-risk patients were alive at last follow-up. FLAG-Ida was well tolerated and effective in our pediatric AML population with no TRM, excellent early disease response by MRD, and encouraging albeit early EFS and OS. This compares favorably with the adult MRC AML 15 experience as well as with the COG DA/ADE regimen, particularly for MRD response (in AAML0531, ~30% patients were MRD+ following Induction I [Brodersen et al 2020]). These data support our continued use of FLAG-Ida in pediatric AML alone or in combination with targeted and/or molecular therapies. Further study of FLAG-Ida as frontline therapy in children with AML is warranted. Figure 1 Figure 1. Disclosures Gaynon: Takeda pharmaceuticals: Other: member of DSMC committee. Orgel: Jazz Pharmaceuticals: Consultancy.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4730-4730
Author(s):  
Omur Gokmen Sevindik ◽  
Zubeyde Nur Ozkurt ◽  
Can Boga ◽  
Sevgi Kalayoglu Besisik ◽  
Yildiz Ipek ◽  
...  

Abstract Introduction: To investigate the demographics and treatment details of the myeloma patients who were diagnosed and followed up in Turkey and received up to two lines of therapy. Methods: Patients who were recorded on the database of Turkish Myeloma Registry project were included in this study if they had only received one or two lines of therapy. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. Results: A total of 532 patients were included in the study, and 44% of the patients were female. Median age at the time of diagnosis was 63 (30-106). 47.7% of the patients were diagnosed with IgG myeloma. According to the ISS risk stratification, 20.4% of patients had ISS 1, 34.7% of patients had ISS 2 and remaining 44.9% had ISS 3 disease. Defining high risk disease as harboring one or more of these following cytogenetic abnormalities; del 17p, t(4;14), t(14;16) or t(14;20); 7.1% of the patients were classified as having a high risk disease. Most commonly used frontline therapy approach was bortezomib cyclophosphamide dexamethasone combination (VCD) (76.5%) and followed by bortezomib dexamethasone (VD) (8.8%), and bortezomib lenalidomide and dexamethasone combination (VRd) (7.1%). Overall response rates (a better response than stable disease according to IMWG response assessment criteria) were 87.6% in VCD induced patients; 63.3% in VD induced patients and 92% in VRd induced patients. The PFS obtained by these frontline approaches was 17.8 months in patients who were able to proceed with high dose chemotherapy with ASCT support and 8.4 in patients who were not able to (p<0.01), with an overall PFS of 15.3 months. With regard to the induction approach, PFS was 21.1 months for VRD, 15.3 months for VCD and 7.6 months for VD (p=0.08). Regarding maintenance, 23.6% of patients were maintained by lenalidomide alone, 62.7% of patients were maintained by a combination of lenalidomide and dexamethasone or bortezomib alone (2.7%). PFS after the first line of the treatment was 22.2 months in maintained patients and 12.2 in un-maintained patients (HR: 0.532, p=0.001, CI95% 0.359-0.790). Regarding the second line therapy Rd was the leading option (34.8%) and VRd (17.8%), Carfilzomib based (16.3%), VCD (8.1%) were the followings. Conclusion: As the main concern of this study was to document the demographic features and clinical parameters of a Turkish Myeloma population and to give an idea about the treatment patterns and outcomes in frontline setting and first relapse an overall survival was not calculated. Progression free survival obtained after frontline therapy was relatively shorter than the ones which were presented by other real- world registries. Outcomes of second line therapy will be presented as follow up after 2nd line therapy exceeds a certain threshold. We hope, the results obtained from this study can have a role in the approval and re-imbursement of the current standard of care options. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2465-2465
Author(s):  
Christopher J. Forlenza ◽  
Jaclyn Rosenzweig ◽  
Audrey Mauguen ◽  
Ilia Buhtoiarov ◽  
Branko Cuglievan ◽  
...  

Abstract Background: Although the prognosis for children with Hodgkin lymphoma (HL) is excellent, up to 25% of patients experience relapse and require salvage therapy. Event-free survival (EFS) for patients with relapsed or refractory disease (R/R) who require high-dose therapy with autologous stem cell transplantation (ASCT) is between 31-67% (Daw, 2011), and efforts to improve these outcomes are an area of urgent clinical need. Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate combined with monomethyl auristatin E. The phase III AETHERA study (NCT01100502) was a randomized, placebo-controlled trial that demonstrated consolidation with BV following ASCT for adults with R/R HL improved progression-free survival (PFS) in comparison to placebo (5-year PFS 59% vs. 41%) in patients identified as having a high-risk of post-ASCT progression (Moskowitz, 2015, 2018). However, there is limited data on post-ASCT BV consolidation in pediatric patients. Here, we report a retrospective multi-center study of BV as consolidation post-ASCT in pediatric patients with R/R HL. Patients and Methods: We performed a retrospective analysis of pediatric patients aged ≤ 21 years who received BV as consolidative therapy following ASCT for the treatment of relapsed/refractory HL. Data was collected on disease risk factors (refractory disease or relapse ≤ 12 months after frontline therapy, best response of partial remission or stable disease to salvage therapy, presence of extranodal involvement, presence of B symptoms, and number of systemic treatments pre-ASCT ≥ 2), treatment history, BV-related toxicity, and response to therapy. The primary endpoint was 3-year EFS. Events were defined as relapse, progression of disease, or death from any cause. Results: Seventy patients were identified from 14 academic centers. Eighteen received BV >90 days after ASCT and were excluded due to significant delay in initiation of BV. Of the remaining 52 patients, the median age at diagnosis was 15 years (range 4-21), and the median age at diagnosis of R/R disease was 16 years (range 8-22). Twenty-eight patients (54%) were male, 13 (25%) had B symptoms, 19 (37%) had extranodal disease. Six patients (12%) had primary refractory disease and 24 patients (47%) relapsed <12 months after frontline therapy. The median number of salvage regimens received pre-ASCT was 2 (range 1-7). Forty-two patients (81%) received BV as part of a pre-ASCT salvage regimen, 4 (8%) of whom did not receive BV in the regimen immediately prior to ASCT. Radiation therapy was used pre or post-ASCT in 16 patients (31%). Prior to ASCT, 40 patients (77%) were PET-negative (Deauville 1-3), 11 (21%) were PET-positive (Deauville 4-5), and response in 1 (2%) was unknown. The median time from ASCT to the start of BV consolidation was 52 days (range 30-90 days). The most frequent adverse events were peripheral neuropathy of any grade (sensory 19/52 [37%]; motor (14/52 [27%]), and cytopenias (grade 3 or 4: (25/52 [48%]), including neutropenia (13/52 [25%]), thrombocytopenia (7/52 [14%]), and anemia (5/52 [10%]). Three patients (6%) experienced infusion-related reactions. The median number of BV cycles completed post-ASCT was 12 (range 1-17), and 16 patients (31%) completed the full 16 cycles of BV. The most common reason for premature termination was adverse effects (22/36 [61%]). Additional reasons included: physician plan for shorter duration (4/36 [11%]), patient/family decision (3/36 [8%]), and progression (1/36 [3%]). Treatment was still ongoing in 3 patients and reason for premature termination was not reported for 17/36 patients (47%). With a median follow of 2.8 years (range 0.1 to 6.25 years) the three-year EFS was 92% [95%CI: 83-100]. Patients with 0-1 risk factors (15/52 [29%]) and ≥ 2 risk factors (37/52 [71%]), had a 3-year EFS of 100% and 90% [95%CI: 79-100], respectively. Fifty patients (96%) are alive with no evidence of disease, while 2 (4%) patients are alive with disease. No deaths have occurred. Conclusion: The use of post-ASCT BV consolidation for pediatric patients with R/R HL is associated with a favorable safety and tolerability profile. In this cohort, the combination of salvage therapy, HD-chemotherapy/ASCT, and BV consolidation resulted in extremely promising outcomes and warrants further investigation in a prospective pediatric trial. Figure 1 Figure 1. Disclosures Leger: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbott Diagnostics: Research Funding. Roth: Merck: Consultancy; Janssen: Consultancy.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3996-3996
Author(s):  
Serageldin Kamel ◽  
Li-Wei Chen ◽  
Gregory Ravizzini ◽  
Ho-Feng Chen ◽  
Joo Schmidt ◽  
...  

Abstract Background: Hodgkin's lymphoma (HL) is a curable malignancy. However, some patients are refractory to frontline therapy. Early prediction of response to frontline therapy could identify patients who may benefit from more intensive therapy. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has an established role in the management of HL. Radiomic features provide a way of quantifying imaging phenotypes and have shown promising results as predictors of outcomes in different lymphomas. Furthermore, great interest has been focused on the heterogeneity of standardized uptake value (SUV) within a single lesion. Since high SUV component (HSc) and low-SUV component (LSc) regions within a single lesion may be associated with different phenotypical characteristics, the radiomic analysis for each regional SUV component may provide a more complete description of lesions. Therefore, we proposed and evaluated new descriptors to quantify the image phenotypes based on HSc and LSc of lesions in HL. Methods: A total of 61 patients with HL of all stages who were seen at MD Anderson Cancer Center between 2016 and 2020 and had analyzable pre-treatment PET/CT were selected. All patients received standard of care ABVD or AVD regimens with or without radiation (Table 1A). Pre-treatment PET/CT scans were analyzed, and HL lesions were semi-automatically segmented using MIM 7 (Cleveland, OH) based on a SUV max threshold of 2.5. Manual edits were made and reviewed by a nuclear medicine physician and a lymphoma specialist. A total of 110 radiomic features were extracted from the segmented lesions in CT and PET using the open-source package of 'PyRadiomics' (Table 1B). Detailed description and algorithms of the extracted radiomics features are available at https://pyradiomics.readthedocs.io/en/latest/features.html. Additionally, each lesion was partitioned into HSc and LSc based on a cutoff value of 3 times the liver SUV mean (Figure A). The ratio of features between SUV components (HSc, LSc) and the lesion area was calculated. Furthermore, the feature difference between HSc and LSc was obtained. The maximum, minimum, average, and standard deviation of the radiomic features within multiple lesions were computed to reveal the distribution of features. A sequential forward feature selection was applied to select the significant features for building a logistic regression model, to predict refractory disease according to Lugano criteria. Two logistic regression models were constructed for early and advanced stage patients. Quantitative measures, namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUV max were measured for comparison. The leave-one-out-cross-validation (LOOCV) was applied to yield the receiver-operator-characteristics curve; the area under the curve (AUC) was then computed to evaluate the performance of the proposed model compared to quantitative measurements using DeLong's test. Results: The average of small dependence high gray level emphasis (GLDM) from PET, the difference of major axis length between high- and low- SUV component from PET, and the difference of 10th Percentile (histogram) between high- and low- SUV component from PET were selected for identifying the refractory disease in early stage lesions; the maximum of correlation (GLCM) from PET, SD of small dependence emphasis (GLDM) from PET, and SD of the inverse difference moment normalized (GLCM) from PET were selected for identifying refractory disease in advanced stage lesions. Based on LOOCV, the proposed radiomics model achieved an AUC of 0.93 for refractory disease prediction, which was significantly superior to MTV (AUC, 0.66; P = 0.01), TLG (AUC, 0.64; P = 0.01), and SUV max (AUC, 0.61; P = 0.01) (Figure B) Conclusion: High and low SUV components-based radiomic model of PET/CT was potentially useful for upfront prediction of refractory HL. Validation in a larger cohort using different segmentation methods, inclusion of additional treatment subgroups, comparison to other predictors, and correlation with survival outcomes are underway. Figure 1 Figure 1. Disclosures Ahmed: Seagen: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Research Funding. Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Pinnix: Merck Inc: Research Funding. Wang: Molecular Templates: Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; Hebei Cancer Prevention Federation: Honoraria; Bayer Healthcare: Consultancy; Mumbai Hematology Group: Honoraria; Pharmacyclics: Consultancy, Research Funding; BioInvent: Research Funding; Celgene: Research Funding; Physicians Education Resources (PER): Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Scripps: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Dava Oncology: Honoraria; Epizyme: Consultancy, Honoraria; Clinical Care Options: Honoraria; BGICS: Honoraria; CAHON: Honoraria; VelosBio: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; Genentech: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; CStone: Consultancy; Newbridge Pharmaceuticals: Honoraria; Juno: Consultancy, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Chinese Medical Association: Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Oncternal: Consultancy, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; OMI: Honoraria; Moffit Cancer Center: Honoraria; Lilly: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2435-2435
Author(s):  
Eduardo Saul ◽  
Juan Pablo Alderuccio ◽  
Isildinha M. Reis ◽  
Wei Zhao ◽  
Sunil G. Iyer ◽  
...  

Abstract Background The most common subtype of B-cell lymphomas presenting in the conjunctiva is extranodal marginal zone lymphoma (EMZL), accounting for ~80% of cases. Most patients (pts) present with localized disease, and radiation therapy (RT) is the preferred treatment strategy. We aimed to retrospectively analyze our single-institution experience to provide further insight into the characteristics and long-term outcomes of conjunctival EMZL. Methods We evaluated 72 pts diagnosed with conjunctival EMZL between 01/1995 and 12/2020 at the University of Miami. Pts' characteristics included age, sex, TNM-AJCC ocular lymphoma and Ann Arbor staging systems, MALT-IPI score, treatment (RT, chemotherapy, rituximab), and treatment response (complete response (CR), partial response, stable disease, progression of disease). Primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meier method, and compared using the log rank test and the univariable Cox regression analysis. We also performed a competing risk univariable analysis (UVA) assessing predictors of cumulative incidence of relapse/progression, with death without relapse as a competing risk, using the Fine and Gray regression analysis. Results Among all 72 pts, mean age was 59.9 yrs (7-93) with 38 (52.8%) being >60 yrs old, 46 (63.9%) were female, 56 (77.8%) had unilateral conjunctival disease, localized disease (T1N0M0 and Ann Arbor stage I) was present in 63 (87.5%), 6 (8.3%) had disseminated disease with more than 1 extranodal site involved, and 29 (40.3%) had a MALT-IPI of 1 or 2. After biopsy and surgical removal, 65 (90.2%) received additional treatment, while 6 (8.3%) were followed only, and in one case therapy information was not available . RT was the most common treatment (53 pts [73.6%], with 46 [86.8%] of those treated with ≥ 30 Gy). In two of these patients RT was combined with chemotherapy. Other treated pts received immunochemotherapy (12 [16.7%], including rituximab in 8). Five pts with stage II-IV disease received systemic therapy. CR was achieved in 63 (87.5%) after first line treatment, and no high-grade lymphoma transformation was seen. With a median follow up of 6.67 yrs (0.56-24.13), there were 14 relapses (19.4%). Among 53 pts treated with RT there were 8 relapses (15.1%), only one (1.9%) within the RT field. There were 23 progression events (31.9%, 14 relapses and 9 deaths without documented relapse), and a total of 14 deaths (19.4%). Mean PFS and OS were 6.69 yrs (0.49-20.37, SD 4.95) and 7.81 yrs (0.56-24.13, SD 5.40), respectively. The 10-yr PFS and OS were 68.4% (95%CI 52.8, 79.8%) and 89.4% (95%CI 77.4, 95.2%), respectively. Variables associated with shorter PFS in UVA Cox model were age > 60 yrs (HR=2.93, 95%CI 1.08, 7.95; p=0.035), high MALT-IPI (1-2) (HR=2.42, 95%CI 1.01, 5.78; p=0.048), and use of chemotherapy only (HR=2.73, 95%CI 1.13, 6.56; p=0.025). Variables associated with shorter OS included age >60 yrs (HR=9.07, 95%CI 1.17, 70.26; p=0.035) and high MALT-IPI (HR=6.19, 95%CI 1.35, 28.33; p=0.019). CR after frontline therapy was associated with longer PFS (HR=0.13, 95%CI 0.04, 0.45; p=0.001) but not OS. PFS of MALT-IPI 0 vs 1-2 was significantly longer (p=0.042), with 10-yr PFS 80.9% (95%CI 63.4%, 90.6%) vs 55.6% (95%CI 32.1%, 73.8%). Similarly, longer OS was observed in MALT-IPI 0 pts (p=0.0077; 10-yr OS 95.2% [95%CI 82.2%, 98.8%] vs 80.6% [95%CI 55.6%, 92.4%]) (Figure). A subset UVA Cox analysis of patients with Ann Arbor stage I showed longer PFS associated with CR after frontline therapy (HR 0.15, 95%CI 0.04, 0.58; p=0.006) with no significant association with age >60 yrs, high MALT-IPI or use of chemotherapy. Variables associated with shorter OS were age >60 yrs (HR 8.01, 95%CI 1.00, 63.98; p=0.05) and high MALT-IPI (HR 13.41, 95%CI 1.67, 107.99; p=0.015), similarly to the primary analysis. On univariable Fine and Gray regression models with death without relapse/progression as a competing risk, RT (SHR=0.33, 95%CI 0.12, 0.96; p=0.041) and CR-post frontline therapy (SHR=0.11, 95%CI 0.03, 0.36; p<0.001) were associated with lower risk of relapse. Conversely, chemotherapy (SHR=3.47, 95%CI 1.20, 10.0; p=0.022) was associated with higher risk of relapse. Conclusion Patients with conjunctival EMZL exhibit excellent long-term survival, and RT remains the most effective frontline therapy. MALT-IPI appropriately identifies patients at risk for treatment failure. Figure 1 Figure 1. Disclosures Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member. Lossos: Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; NCI: Research Funding; Stanford University: Patents & Royalties; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4226-4226
Author(s):  
Francis N. Ssali ◽  
Joan Aturinde ◽  
Daniel Muyanja ◽  
Cissy Kityo

Abstract Introduction The current International Society on Thrombosis and Hemostasis (ISTH) guideline of Thrombotic Thrombocytopenic Purpura (TTP) recommends Therapeutic Plasma exchange (TPE) and corticosteroid in the management of TTP, with Rituximab and Caplasizumab as additional potential therapies [X Long Zheng et al, J Thromb Haemost. 2020;18:2496-2502]. This potentially fatal condition requires prompt diagnosis and treatment but large volume plasma treatment is not without risk and in settings with limited access with sufficient compatible plasma for apheretic exchange, this can delay this emergency therapy. We have been running the first therapeutic apheresis services with an Optia instrument in Uganda at the Joint Clinical Research Centre in Kampala city and TTP is the main indication for TPE. We present 2 recent sequential cases of TTP that were successfully managed when Bortezomib was combined with plasma therapy. Case1. A 25yr woman referred to our service on 29/09/2020, with recent onset of bruising, icterus, severe anemia Hgb5.7g/dL, Severe thrombocytopenia 8 x 10 3/uL, a high LDH 3909U with schistocytes on the peripheral blood film severe thrombocytopenia and a negative Direct Antiglobulin test. She was Blood Group B+. She was managed with 3 sessions of TPE of 2.1, 1.1 and 2.0 plasma volume exchanges with 6727mL, 3026mL and 5459mL of replacement plasma respectively and oral prednisone 60mg daily without remission. Subsequent quantities of plasma were insufficient for apheresis and were instead transfused. She also received weekly Rituximab 500mg (IV) but without significant recovery in the platelet count until she received Bortezomib 2mg (SC) when there was corresponding recovery of the platelet count and with each dose to a total of 4 doses (Figure 1). Case2. A 55yr man was previously well and shopping in a mall when he had an index episode of seizures on 19.Jun.2021 and was hospitalized that day with altered consciousness and focal motor signs. He required intubation for 3 days and at the time of hospitalization, he had Hgb 9gm/dL, PLT 17 x 10 3/uL, LDH2177U, with numerous schistocytes on the peripheral blood film and a negative Direct Antiglobulin Test. The baseline blood sample functional ADAMTS13 was 3% and had Blood Group AB+. He had received the 1 st dose of the Astra-Zeneca Covid19 vaccine on 06.May.2021. It was not possible to get any AB plasma and we considered it risky to perform large volume TPE with non-AB plasma and he was instead treated with daily transfusion with Group A+ Plasma concurrent with daily Prednisone 60mg. Because of our previous experience of poor response to Rituximab, we opted to treat him upfront with 4 doses of 2mg bortezomib (SC) given 3 days apart. He made brisk recovery to complete remission and was discharged for weekly outpatient CBC and LDH monitoring. His platelet count subsequently dropped without a corresponding drop in the Hgb and no rise in the Hgb. We initially re-hospitalized him for 4 more days of plasma transfusion but without a brisk response and since the LDH was not increasing, the isolated Thrombocytopenia was considered a side effect of Bortezomib that was expected to resolve and he receive no further treatment but continued to recover to complete remission as an out-patient (figure 2). Discussion: Our findings suggest a possible role for Bortezomib in frontline therapy for TTP with potential to reduce the plasma requirement in TPE and this approach warrants a randomized clinical trial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Bortezomib Indicated in the management of Multiple Myeloma and Plasma Cell Dyscrasia


2021 ◽  
Vol 11 ◽  
Author(s):  
Xia Bi ◽  
Sabarina Ramanathan ◽  
Gina Keiffer

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