Extranodal Sites Research Articles

Prevalence of Non-Hodgkin Lymphoma Patients at High Risk of Failure after CAR T-Cell Therapy Eligible for Bridging Radiation Therapy.

CD19-directed chimeric antigen receptor T-cell therapy (CART) has led to remarkable outcomes in patients with relapsed or refractory (R/R) non-Hodgkin's lymphomas (NHL), yet ∼50% of patients relapse. Predictive factors associated with high risk of relapse following CART have been identified in the literature. Studies have shown a potential improvement in outcomes with the use of bridging radiation (RT) prior to CART. The purpose of this study is to determine the incidence of patients meeting high risk criteria who have disease that could be encompassed in a standard radiation plan prior to CART. This was a single-center, retrospective study of patients with R/R NHL who received CART from 2018 to 2022. Data were obtained from the EHR and manual chart review was used to identify patients with disease encompassable in a standard radiation plan defined as <5 malignant lesions on pre-apheresis radiological studies. These patients were then screened for presence of ≥1 high risk criteria: bulky disease ≥10 cm, ≥1 extranodal (EN) sites, LDH ≥normal, or ≥1 lesion with SUVmax ≥10. Descriptive statistics were used to make inferences about the population. Eighty-one R/R NHL patients were evaluated with a median age of 65 years (range 23-84), 60% male, and received a median of 2 (range 1-7) prior lines of therapy. CART products included axi-cel (62%), brexu-cel (7%), liso-cel (16%), and tisa-cel (15%). Forty (49%) patients would have been eligible for bridging RT (<5 sites on pre-apheresis radiologic studies), including 29 patients who met high risk criteria: 19 had ≥1 lesion with SUVmax ≥10, 16 with bulky disease, 6 with ≥1 EN site, and 3 with elevated LDH. At 3 months post-CART, clinical response data were available for 19 high risk patients with ORR of 79% (11 CR, 4 PR, 1 SD, and 3 PD), compared to 8 patients with standard risk disease with ORR of 88% (7 CR and 1 PD). Of those with less than a CR, 8/9 met high risk criteria: 4 with bulky disease, 6 had ≥1 lesion with SUVmax ≥10, and 2 with ≥1 EN site. There were 9/40 patients who received bridging therapy, and only 2 high risk patients received bridging RT. One patient with transformed DLBCL had persistent disease in the nasopharynx following RCHOP x3C and R-HyperCVAD, and received 20 Gy/10 fx as a bridge to CART resulting in a continued CR at 23 months of follow-up. Another patient with non-DH, GCB-like DLBCL received R-CHOP x6C (achieved CR) but relapsed <1 year later and then received R-ICE x2C with PD in the left shoulder, which was radiated with 30 Gy/10 fx for pain as a bridge to CART, but experienced disease relapse 6 months after CART. Approximately 35% (28/81) of patients were classified as high risk of relapse after CART and had disease encompassable in a standard radiation plan. Of these patients, 44% (8/18) experienced either PR, SD or PD at 3 months post-CART. Future studies are needed to determine the role of bridging RT prior to CART as a strategy to improve outcomes and prevent relapse in high-risk NHL patients.

Complete Absence of FAPI Uptake in a Patient With Aggressive Diffuse Large B-Cell Lymphoma Involving Multiple Nodal and Extranodal Sites.

A 73-year-old man with histopathologically confirmed diffuse large B-cell lymphoma underwent both 18F-FDG and 18F-FAPI PET/CT. Although 18F-FDG PET showed abnormally increased tracer uptake in multiple nodal sites and organs, indicating the aggressiveness of the disease status, 18F-FAPI PET showed no obvious FAPI uptake in any of the FDG-avid lesions. Our case suggests that low expression of FAP in diffuse large B-cell lymphoma, as indicated by FAPI PET, might help determine a subgroup of patients with poorer outcome.

CCDC50, an essential driver involved in tumorigenesis, is a potential severity marker of diffuse large B cell lymphoma

Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan–Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3β pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients.

Diffuse large B-cell lymphoma involving osseous sites: utility of response assessment by PET/CT and good longterm outcomes.

Osseous involvement by diffuse large B-cell lymphoma (DLBCL-bone) is a heterogeneous disease. There is limited data regarding response assessment by positron emission tomography with fluorodeoxyglucose, which may demonstrate residual avidity despite a complete response. We analyzed clinical data of patients with newly diagnosed DLBCL and identified all cases with DLBCL-bone. End of treatment scans were reviewed by two independent experts classifying osseous lesions into Deauville (DV) ≤3; DV ≥4, or reactive uptake in the bone marrow (M), site of fracture (F) or surgery (S). We compared outcomes of DLBCL-bone to other extranodal sites (EN) matched on International Prognotic Index features and regimen. Of 1,860 patients with DLBCL (bone 16%; EN 45%; nodal 39%), 41% had localized disease and 59% advanced. Only 9% (n=27) of patients with initial bone involvement had residual fluorodeoxyglucose avidity at the osseous site. In half of these cases, the uptake was attributed to F/S/M, and of the remaining 13, only two were truly refractory (both with persistent disease at other sites). Overall survival and progression-free survival (PFS) were found to be similar for early- stage nodal DLBCL and DLBCL-bone, but inferior in EN-DLBCL. Advanced-stage disease involving the bone had a similar 5-year PFS to nodal disease and EN-DLBCL. After matching for International Prognotic Index and treatment regiments, PFS between bone and other EN sites was similar. Osseous involvement in DLBCL does not portend a worse prognosis. End of treatment DV ≥4 can be expected in 5-10% of cases, but in the absence of other signs of refractory disease, may be followed expectantly.

Renal mucosa-associated lymphoid tissue lymphoma: a case report and literature review

Background: Renal MALT lymphoma is a rare entity with few reports in the literature. These neoplasms arise at extranodal sites, usually related with chronic inflammation due to infection or autoimmune disorder and share histologic and immunophenotypic features. To date, 10 cases of renal MALT lymphoma have been described. Case presentation: We present a case of a MALT renal lymphoma in a 69-year-old woman with suspected preoperative diagnosis of renal cell carcinoma (papillary vs chromophobe type), RENAL SCORE 9p. We performed a retroperitoneal laparoscopic left partial nephrectomy guided by intraoperative ultrasound. Conclusion: There are few reports in the literature regarding renal MALT lymphoma. We consider that this might be considered as a differential diagnosis of renal mass.

Cytotoxic peripheral T-cell lymphomas and EBV-positive T/NK-cell lymphoproliferative diseases: emerging concepts, recent advances, and the putative role of clonal hematopoiesis. A report of the 2022 EA4HP/SH lymphoma workshop

Cytotoxic peripheral T-cell lymphomas and EBV-positive T/NK-cell lymphoproliferative diseases were discussed at the 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop held in Florence, Italy. This session focused on (i) primary nodal EBV-positive T and NK-cell lymphomas (primary nodal-EBV-TNKL), (ii) extranodal EBV-positive T/NK lymphoproliferative diseases (LPD) in children and adults, (iii) cytotoxic peripheral T-cell lymphomas, NOS (cPTCL-NOS), EBV-negative, and (iv) miscellaneous cases. Primary nodal-EBV-TNKL is a newly recognized entity which is rare, aggressive, and associated with underlying immune deficiency/immune dysregulation. All cases presented with lymphadenopathy but some demonstrated involvement of tonsil/Waldeyer’s ring and extranodal sites. The majority of tumors are of T-cell lineage, and the most frequent mutations involve the epigenetic modifier genes, such as TET2 and DNMT3A, and JAK-STAT genes. A spectrum of EBV-positive T/NK LPD involving extranodal sites were discussed and highlight the diagnostic challenge with primary nodal-EBV-TNKL when these extranodal EBV-positive T/NK LPD cases demonstrate predominant nodal disease either at presentation or during disease progression from chronic active EBV disease. The majority of cPTCL-NOS demonstrated the TBX21 phenotype. Some cases had a background of immunosuppression or immune dysregulation. Interestingly, an unexpected association of cPTCL-NOS, EBV-positive and negative, with TFH lymphomas/LPDs was observed in the workshop cases. Similar to a published literature, the genetic landscape of cPTCL-NOS from the workshop showed frequent mutations in epigenetic modifiers, including TET2 and DNMT3A, suggesting a role of clonal hematopoiesis in the disease pathogenesis.

Primary Esophageal Mucosa-associated Lymphoid Tissue Lymphoma: A Rare Case Report and Review of Other Published Data

The gastrointestinal tract is the most common extranodal site for lymphomas, and mucosa-associated lymphoid tissue lymphoma is the second most common histological lymphoma subtype. However, primary esophageal mucosa-associated lymphoid tissue lymphomas are extremely rare. Few such cases are documented, and the reports demonstrate inconsistent diagnostic and therapeutic strategies. Herein, a 54-year-old man was referred to our hospital for treatment of dysphagia. Esophagogastroduodenoscopy revealed a large, horseshoe-shaped subepithelial mass in the upper esophagus. Endoscopic ultrasonography and computed tomography revealed that the mass was well-demarcated and confined to the muscularis mucosa, with no abnormalities in other organs or lymph nodes. The mass was presumptively diagnosed as benign, and the patient underwent endoscopic mucosal dissection for pathological confirmation and symptom relief. Pathological examination of the dissection specimen revealed that it was a primary esophageal mucosa-associated lymphoid tissue lymphoma. As the patient had an elevated immunoglobulin G level and &lt;i&gt;Helicobacter pylori&lt;/i&gt; infection, we administered adjuvant eradication therapy. The patient remains under surveillance and is free of lymphoma recurrence 36 months postoperatively. This case report demonstrates that endoscopic resection and &lt;i&gt;H. pylori&lt;/i&gt; eradication are effective treatment strategies for early-stage esophageal mucosa-associated lymphoid tissue lymphoma.

Follicular lymphoma and diffuse large B-cell lymphoma with BCL2 and IRF4 rearrangements in adult patients

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) with concurrent BCL2 and IRF4 rearrangements are rare. It is unclear whether such cases should be classified as large B- cell lymphoma with IRF4 rearrangement or FL/DLBCL-not otherwise specified. We identified 5 adult patients (FL, N=3 and FL/DLBCL, N=2) with concurrent BCL2 and IRF4 rearrangements. The median age at presentation was 77 years, and three patients presented with advanced stage disease. Both nodal and extranodal sites were involved and involvement was not limited to head and neck region. With a median follow-up of 18 months, 1 patient died and 4 patients were alive, including 3 who received chemotherapy and 1 who was observed. The neoplasms were histologically heterogeneous, including grade 2 and 3 FL and DLBCL. Four cases coexpressed CD10, BCL6, BCL2 and MUM1/IRF4. The Ki67 labelling index ranged from 20% to 95%. In 4 patients, the percentage of cells with BCL2 rearrangement was equal to or slightly greater than the cells harboring IRF4 rearrangement. Two cases underwent next generation sequencing tailored for lymphoid neoplasms. Both lacked mutations involving IRF4 and NF-kB pathway genes that are frequently detected in large B-cell lymphoma with IRF4 rearrangement, and one case showed DLBCL-EZH2 type mutations, including KMT2D and BCL2 mutations, similar to 2 previously reported DLBCL with BCL2 and IRF4 rearrangements. Adults with FL and FL/DLBCL with BCL2 and IRF4 rearrangements display clinicopathologic and mutational features more akin to FL and DLBCL and should not be characterized as large B-cell lymphoma with IRF4 rearrangement.

Clinico-Epidemiological Presentation and Treatment Outcome of Peripheral T-Cell Lymphoma– Not Otherwise Specified (PTCL-NOS): A Single Institutional Experience

Background: Peripheral T-Cell Lymphomas (PTCL) are aggressive malignant lymphoproliferative disorders that represent 10-15% of all non-Hodgkin’s lymphomas (NHL). PTCL- not otherwise specified (PTCL-NOS), comprises approximately 6% of all NHLs, which do not meet the criteria for other mature peripheral T-Cell lymphoma as defined in WHO classification. With limited long-term data evaluating the outcome of PTCL-NOS in the Indian population, we aimed to determine the clinico-epidemiological profile and treatment outcome of patients with PTCL-NOS in a cancer care center from North-East India. Material and Methods: A retrospective observational analysis was performed on the medical records of patients who were diagnosed with PTCL-NOS between January 2015 and December 2018 at Dr. B. Borooah Cancer Institute. Results: Our study evaluated fifty-three patients with PTCL-NOS with the mean age at presentation being 45.3 years (SD ± 16.3 years). The majority of the patients (77.3%) presented with advanced stage (III/IV) with bone marrow involvement in 35.8% of the patients. B-symptoms were present in 58.4% of the patients. Extra-nodal sites of involvement were seen in 64.1% of the patients. The anthracycline-based chemotherapy regimen was the most commonly used in the frontline setting in 71.6% of the patients. Radiation therapy (IFRT) was received by 26.4% of the patients. The overall response rate (ORR) to first-line chemotherapy was 94.3% with complete response (CR) achieved by 62.3% of patients. Twenty-nine (58%) patients had relapsed/ progressive disease. With a median follow-up duration of 38 months, the 3-year progression-free survival (PFS) rate and 3-year overall survival (OS) rate were 27.6% and 33.9% respectively. The median PFS was 22 ± 3.3 months and the median OS was 28 ± 7.1 months.Conclusion: PTCL-NOS is one of the aggressive subtypes of NHL with limited therapeutic options and poor outcomes. Proper treatment adherence and the availability of newer therapeutic options can further enhance the overall outcome.

Marginal zone lymphoma: 2023 update on diagnosis and management.

Marginal zone lymphomas (MZL) are collectively the second most common type of indolent lymphoma. Three subtypes of MZL are recognized:splenic, extranodal, and nodal. The diagnosis is secured following biopsy of an involved nodal or extranodal site demonstrating a clonal B-cell infiltrate with CD5 and CD10 negative immunophenotype most common. Some cases will features IgM paraprotein, but MYD88 L256P mutations are less frequent than in Waldenstrom macroglobulinemia. Prognostication Several prognostic models have been developed, including the MALT-IPI and the MZL-IPI. The latter is broadly applicable across MZL subtypes and incorporates elevated serum LDH, anemia, lymphopenia, thrombocytopenia and nodal or disseminated subtypes as independent predictors of outcome. We discuss suggested approach to therapy for both early and advanced-stage disease, with reference to chemo-immunotherapy, radiotherapy, and emerging treatments in relapsed/refractory disease such as BTK inhibitors.

P04 Leg ulceration in a patient with antisynthetase syndrome

Abstract A 42-year-old woman presented with leg ulceration on a background of antisynthetase syndrome and immunosuppression with rituximab, azathioprine and prednisolone. The initial lesion was an erythematous patch on the lower leg, which increased in size with violaceous changes. The area subsequently broke down to form an ulcer. On examination, she had a 7-cm ulcerating lesion with central necrosis. Clinically, the appearance was suspicious of pyoderma gangrenosum; biopsy demonstrated scarring without features of vasculitis, atypia or malignancy. The ulcer did not show improvement as expected after oral and topical steroid treatment, with new fleshy nodular growth. Repeat biopsy showed angiocentric atypical lymphocytes with positive Epstein–Barr virus (EBV)-encoded RNA (EBER) staining. Further incisional biopsy demonstrated large, atypical B lymphocytes with a diffuse sheet-like morphology and a poorly circumscribed base. Immunohistochemistry was positive for CD79a, CD30, CD20, MUM1, BCL6, and EBER. Overall, the findings were consistent with EBV-positive diffuse large B-cell lymphoma (DLBCL). The main differential diagnosis was EBV-positive mucocutaneous ulcer (MCU), another EBV-associated lymphoproliferative disorder, albeit with an indolent course (Dojcinov SD, Venkataraman G, Raffeld M et al. EBV positive mucocutaneous ulcer—a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010; 34:405–17). In this case, the diffuse sheet-like morphology and poorly circumscribed base favoured EBV-positive DLBCL. The lesion fully healed with withdrawal of immunosuppression and treatment with rituximab therapy, and involved field radiotherapy. First described in 2003, EBV-positive DLBCL is a rare, classically aggressive lymphoma initially believed to only occur in patients older than 50 years of age (Oyama T, Ichimura K, Suzuki R et al. Senile EBV+ B-cell lymphoproliferative disorders. Am J Surg Pathol 2003; 27:16–26). Since the revision of the World Health Organization classification in 2016, it is also recognized to present in younger patients, with an associated better prognosis. EBV-positive DLBCL occurs in both nodal and extranodal sites. Therefore, cutaneous presentations must complete staging investigations to rule out skin involvement secondary to a nodal lymphoma. Our patient highlights a rare complication of immunosuppression. We illustrate the relevance of considering rare causes of ulceration in patients with autoimmune conditions and immunosuppression and demonstrate the importance of considering malignancy in a nonhealing ulcer. Multiple biopsies may be needed in ulcers that poorly respond to treatment. While EBV-positive DLBCL and EBV-positive MCU can be difficult to differentiate, it is vital for prognostication.

Primary Extranodal Non-Hodgkin Lymphoma of Cheek

Non-Hodgkin’s lymphomas (NHL) comprise a group of extremely diverse lymphoproliferative neoplamas that have a predisposition for extranodal sites. Amongst the extranodal locations rare involvement of oral cavity has been reported and occurrence of these neoplasms on the cheek are thin on the ground. The most commonly encountered is the Diffuse large B-cell lymphoma. The B-cell neoplasms are clonal tumors of mature and immature B cells and the relatedness of B-cell lymphomas to normal B-cell counterparts forms a key aspect in their nomenclature of classification. Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), consists of medium-sized to large B cells with a diffuse growth pattern. This lesion is a morphologically and molecularly heterogeneous entity which does not meet the diagnostic criteria of any specific large B-cell lymphoma neoplasms. Amongst the cases of DLBCL in n the head and neck region involvement of cheek/ buccal mucosa is scarce.

Multi-site pre-therapeutic biopsies demonstrate genetic heterogeneity in patients with newly diagnosed diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, both regarding clinical presentation, response to treatment and outcome. Recently, subclassification of DLBCL based on mutational profile has been suggested, and next generation sequencing (NGS) analysis may be relevant as part of the diagnostic workflow. This will, however, often be based on analysis of one tumor biopsy. Here, we present a prospective study where multi-site sampling was performed prior to treatment in patients with newly diagnosed DLBCL. Two spatially different biopsies from 16 patients were analyzed using NGS with an in-house 59-gene lymphoma panel. In 8/16 (50%) patients, mutational differences were found between the two biopsy sites, including differences in TP53 mutational status. Our data indicate that a biopsy from the extra-nodal site may represent the most advanced clone, and an extra-nodal biopsy should be preferred for analysis, if safely accessible. This will help ensure a standardized stratification and treatment decision.

Rosai-dorfman disease in pregnancy with rare presentations – A case report

Rosai-Dorfman disease (RDD) also known as sinus histiocytosis with massive lymphadenopathy is a rare disorder of histiocytes characterized histologically by intracellular engulfment of lymphocytes. It may occur in any age group, but is most commonly seen in children and young adults. It is characterized by painless, bilateral massive cervical lymphadenopathy. In approximately one-third of patients it can occur in a variety of extranodal sites where it can have abundant plasma cells and sclerosis. We present a rare case of RDD in a pregnant women who presented with unilateral cervical lymph node with features of RDD showing increase in plasma cells and sclerosis as seen in extranodal sites.

PROGNOSTIC SIGNIFICANCE OF CD30 EXPRESSION IN DIFFUSE LARGE B-CELL LYMPHOMA: A SYSTEMATIC REVIEW WITH META-ANALYSIS

Objective To determine the frequency of CD30 expression in DLBCL and its potential for prognostic determination. Study Design A systematic review was performed, followed by a quantitative meta-analysis to assess the frequency of CD30 expression with positivity cut-off values of >0% and >20%, and determine its association with clinicopathological features and patient survival. Results Using a cut-off value >0%, we observed that 3.5%-59.1% of the cases were considered positive for CD30. There was a significant association of the protein expression with a lower number of extra-nodal sites affected by the neoplasm, with Ann Arbor advanced stage, the absence of B-symptoms, the lack of MYC and BCL2 translocations, and a lower ECOG performance. Using a cut-off value >20%, we observed that 2.5%-36.7% of the cases were considered positive for CD30, being significantly associated with a lower number of extra-nodal sites affected by the neoplasm, Ann Arbor stages III/IV, non-GCB tumours, the lack of MYC and BCL2 translocations, and a lower ECOG value. Conclusion Despite variations in the cut-off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis. To determine the frequency of CD30 expression in DLBCL and its potential for prognostic determination. A systematic review was performed, followed by a quantitative meta-analysis to assess the frequency of CD30 expression with positivity cut-off values of >0% and >20%, and determine its association with clinicopathological features and patient survival. Using a cut-off value >0%, we observed that 3.5%-59.1% of the cases were considered positive for CD30. There was a significant association of the protein expression with a lower number of extra-nodal sites affected by the neoplasm, with Ann Arbor advanced stage, the absence of B-symptoms, the lack of MYC and BCL2 translocations, and a lower ECOG performance. Using a cut-off value >20%, we observed that 2.5%-36.7% of the cases were considered positive for CD30, being significantly associated with a lower number of extra-nodal sites affected by the neoplasm, Ann Arbor stages III/IV, non-GCB tumours, the lack of MYC and BCL2 translocations, and a lower ECOG value. Despite variations in the cut-off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis.

Diffuse large B-cell lymphoma in HHV8+ multicentric castleman disease: A national analysis of demographic features.

e19535 Background: Diffuse large B-cell lymphoma (DLBCL) in human herpesvirus 8 associated (HHV8+) multicentric Castleman disease (MCD) is a rare type of DLBCL. DLBCL, the most common non-Hodgkin lymphoma, is a cancer arising in the lymphatics. HHV8+ MCD is a lymphoproliferative disorder usually occurring in HIV patients. Patients who develop DLBCL in this setting typically die within a year. Prior National Cancer Database (NCDB) studies have assessed survival and demographics in the broader category of CD20- LBCLs, but have not specifically examined the socioeconomic and demographics associated with DLBCL in HHV8+ MCD. Methods: A retrospective analysis of NCDB data from 2010 – 2020 included patients diagnosed with DLBCL in HHV8+ MCD (N = 237). Demographic factors such as sex, race, Hispanic ethnicity, income status, insurance status, Charlson-Deyo score, facility type/location, and metastasis at diagnosis were evaluated with descriptive statistics. Primary site was also examined. Incidence trends were assessed via regression analysis. Results: A total of 237 patients with DLBCL in HHV8+ MCD were identified in the database, with an average incidence of 21.5 cases per year (R2 = 0.236, SD = 5.7, range = 9 – 29). 74.7% were male and the average age of diagnosis was 53.8 years (SD = 18.62, range = 3 – 90). 40 different primary sites were identified, with the most common being lymph nodes of multiple regions (32.9%). Extranodal primary sites were rare but documented. Charlson-Deyo comorbidity scores varied: Score 0 = 61.6%, Score 1 = 8.4%, Score 2 = 4.2%, Score ≥ 3 = 25.7%. Incidence for race was highest among Whites (69.2%), followed by Blacks (25.3%), then Asians (3.4%). 8.4% of patients were of Hispanic ethnicity. A greater percentage of patients were in the top income quartile (33.8%), compared to the second (19.7%), third (23.9%), and fourth (22.5%). Most patients were either insured privately or by Medicare (73.9%), whereas 8.9% were uninsured. Most were treated at academic facilities (54.7%), and many were treated at facilities in the Eastern United States (47.5%). 19.1% of patients had metastases at diagnosis, most often in distant lymph nodes (6.1%). Conclusions: This study provides insight into the demographics of patients diagnosed with DLBCL in HHV8+ MCD. This cancer showed a nearly 3-fold male preponderance and primarily affected Whites, mirroring existing trends in DLBCL overall. About one fifth of patients presented with metastasis at diagnosis. Interestingly, patient Charlson-Deyo scores displayed a bimodal distribution, with 87.3% of patients having a Score of either 0 or ≥3. The top income quartile was most affected, but patients were more evenly distributed among the bottom three. Further investigation is needed to better define the role of demographics in shaping diagnostic, therapeutic, and outcome discrepancies in those with DLBCL in HHV8+ MCD.

RADIOTHERAPY BRIDGING IN LARGE B‐CELL LYMPHOMA PATIENTS RECEIVING CD19 CAR‐T – THE UK EXPERIENCE

Background: Radiotherapy (RT) has potential synergistic effects with CAR T but is not widely used as bridging therapy for lymphoma patients due to logistical challenges, uncertainty about patient selection and lack of standardised protocols. Published data on RT bridging are so far restricted to single-centre analyses. Methods: We analysed RT bridging in a large multi-centre national cohort of large B-cell lymphoma (LBCL) patients approved for 3rd line axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between December 2018 and October 2022 across 12 UK centres. Results: Of 763 approved patients, 722 (95%) were leukapheresed, 717 had data available on bridging therapy. 170/717 (24%) received RT bridging, 129 as single modality and 41 as combined modality treatment (CMT). Use of RT bridging varied between centres from 11% to 32%, and increased from 19% (2018–19) to 26% (2021–22; p = 0.034). Median age of RT bridged patients was 60 y. 69% had de novo LBCL, 8% PMBL, 35% tFL and 6% transformed from other low-grade lymphoma. Disease characteristics for RT bridged patients with available data were as follows: 66% advanced stage, 41% bulk, 87% elevated LDH, 42% IPI ≥ 3, 17% double/triple hit. Patients given single modality RT were less likely to have advanced stage or ≥2 extranodal sites versus those receiving systemic therapy/CMT (61% vs. 85/83% and 18% vs. 30/39%, respectively; p < 0.05). Median time from approval to infusion was 56 days with no difference between bridging modalities. Infusion rates were 88% for RT bridging (vs. 84%, 85%, 85% for no bridging, steroids, or systemic therapy, respectively (p = 0.41)). Data on bridging (in-field) response was available for 46 RT patients: 10% CR, 65% PR, 6% SD, 10% PD. Details on RT techniques, anatomical locations and toxicities were available for 68 patients and will be provided at the meeting. Doses of 2–39 Gy were used, including combination of multiple doses; 40 patients received IMRT. Only one patient experienced G3–4 toxicity from RT. The overall incidence of G ≥ 3 CRS was 5.2% and G ≥ 3 ICANS 16.3%, with no significant difference according to bridging approaches. Median follow-up was 16 months. RT bridged patients had favourable outcomes with 1-y PFS of 56% for single modality and 47% for CMT, and 1-y OS of 65% and 56%, respectively (Figure 1). RT bridging was associated with favourable outcomes both in limited and advanced stage (1-y PFS 59% (43—72) and 50% (39–61), respectively. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, radiation therapy Conflicts of interests pertinent to the abstract A. Kuhnl Consultant or advisory role: Kite/Gilead, Novartis, BMS Honoraria: Kite/Gilead, Novartis A. Kirkwood Honoraria: Kite/Gilead A. Gibb Consultant or advisory role: Kite/Gilead A. Latif Honoraria: Kite/Gilead, Novartis

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients (pts) with relapsed/ refractory (r/ r) LBCL (DLBCL, tFL, PMBCL). Anti-CD19 CAR T-cells (CART) entered the clinical arena around 5 years ago now being considered standard of care for such patients. As >50% of LBCL pts progress or relapse after CART treatment we were interested in identifying prognostic factors for both modalities and their relative role in the treatment of advanced r/r LBCL. Methods: Pts registered with the EBMT database from 1/2016 to 5/2021 having received either a first alloSCT or commercially available CART therapy (Yescarta® or Kymriah ®) as ≥3rd therapy of LBCL were analyzed. To correct for imbalances in patient characteristics we did propensity score analyses considering only pts with complete information on IPI including LDH at the time of cell therapy. We performed multivariate analyses in patients with either low- or high-risk r/r LBCL according to LDH level at cell therapy in pts treated with alloSCT or CART. Results: We identified 515 pts with full information on IPI at cell therapy (212 alloSCT and 303 CART). Patient groups differed significantly in median age, IPI score, and disease status at cell therapy. Median follow up was 46.3 months after alloSCT and 22.1 months after CART treatment. In univariate analysis, type of cell therapy, disease status, and IPI at cell therapy had a significant impact on OS. Amongst IPI risk factors LDH, performance status, and number of extranodal sites had a significant impact on OS, PFS an RI. At 24 months, OS was 41% after allo SCT and 49% after CART. In a propensity score analysis using all IPI factors as covariates, CART was superior to alloSCT in terms of OS (HR 0.62, 95% CI: 45–0.84, p = 0.0193) but not PFS, RI or NRM. In multivariate analysis patients with IPI (o-2) low risk at cell therapy show better OS (HR 0.81, 95% CI 0.59–1.1, p < 0.0001) and PFS (HR 0.62, CI: 0.46–0.83, p = 0.00145), comparable RI and lower NRM (HR 0.21 CI: 0.11–0.42, p = 0.00001) with CART compared to allo SCT. In IPI (3–5) high-risk patients, CART showed significantly higher RI (HR 1.45, CI: 1.03–2.04, p = 0.03549) but lower NRM (HR 0.21, CI: 0.11–0.42), p = 0.00001) compared to allo SCT. OS and PFS did not significantly differ. Refractory disease was an independent adverse prognostic factor for OS (HR 1.74, CI: 1.3–2.33, p = 0.0002), PFS (HR 1.61 CI: 1.23–2.1, p = 0.0006) and RI (HR 1.79 CI: 1.29–2.49, p = 0.0006) but not for NRM. Results at 2 years are given in Table 1. Conclusion: IPI assessed at cell therapy is of prognostic impact for both CART and allo SCT. Overall, pts given CART for ≥3rd line treatment of DLBCL showed better OS than pts treated with alloSCT. In patients with high intermediate/high IPI results of CART must be improved and allogeneic SCT remains a valuable treatment strategy due to its high anti-lymphoma activity. Keyword: Cellular therapies Conflicts of interests pertinent to the abstract. B. Glass Consultant or advisory role: Kite, BMS, Novartis, Milteneyi, Roche, Janssen, Jazz, Abbvie Honoraria: Kite, BMS, Novartis, Milteneyi, Roche, Janssen, Jazz, Abbvie Research funding: Roche, Riemser A. Sureda Consultant or advisory role: Takeda, MSD, BMS, Novartis, Janssen, Roche, Sanofi, Gilead P. Dreger Consultant or advisory role: Kite, Novartis P. Corradini Honoraria: Abbvie, Amgen, Celgene, Giled, Incyte, Janssen, Takeda, R. Ram Honoraria: Novartis, Gilead, Takeda, BMS G. Wulf Consultant or advisory role: Gilead, Novartis A. M. García-Sancho Consultant or advisory role: Roche, BMS, Kyowa Kirin, Clinigen, Eusa Pharma, Novartis, Kite Gilead, Servier, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Kern M. Stelljes Consultant or advisory role: Medac, Pfizer, Jazz, Novartis, MSD, Amgen, BMS, Kite D. Blaise Consultant or advisory role: Jazz E. Forcade Consultant or advisory role: Gilead, Jazz, Novartis, GSK, Sanofi, MSD I. Hilgendorf Consultant or advisory role: Novartis, Abbvie J. A. Perez-Simon Consultant or advisory role: Novartis, Janssen, Gilead, Jazz, Alexion, Abbvie, Pfizer W. Bethge Consultant or advisory role: Gilead, Novartis, Miltenyi, Janssen, Celgene N. Schmitz Consultant or advisory role: Allogene Stock ownership: BMS Honoraria: Allogene Research funding: Janssen, Roche Educational grants: Allogene, Milteneyi

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: DLBCL that fails to achieve a complete response (CR) or relapses early after standard immunochemotherapy (IC, e.g., R-CHOP or similar) is referred to as primary refractory DLBCL (prDLBCL) and has a poor prognosis. Different definitions of prDLBCL have been used in literature, and it is uncertain which definition of primary refractory correlates most closely with survival outcomes. In this study, we examined the association of time to refractory status with survival outcomes in patients with prDLBCL. Methods: Adult patients diagnosed with DLBCL between 2015 and 2020 and seen at an academic center included in the lymphoma epidemiology of outcomes (LEO) cohort were included. PrDLBCL was defined as no response or progressive disease (PD) during frontline IC (primary progressive disease, PD), partial response (PR) at end of treatment (EOT PR), or relapse with 12 months after achieving CR at EOT (early relapse). Clinical characteristics, treatment and response data (by Lugano 2014 response criteria), and follow-up data were abstracted from LEO. Results: Out of 2747 DLBCL patients, 310 (11.3%) had prDLBCL, 147 with PD, 66 with EOT PR, and 97 with early relapse. No significant differences in age, gender, race, number of extranodal sites, stage, IPI, or cell of origin were found between the 3 groups. The proportion of MYC and BCL2/BCL6 rearrangements or Myc/Bcl2 double expressor was small and not different among the 3 groups. Salvage therapies were mainly platinum based high-dose chemotherapy (57%), MTX-based therapy for CNS relapse (12%), or targeted therapies (9%). Patients with PD had significantly lower CR/PR rates (19.6%/19.6%) to second line therapy compared to patients with EOT PR (32.1%/30.4%) or early relapse (50.6%/19.1%)(P < 0.001). The 2-year overall survival (OS) rate was 31% for patients with PD, which was significantly worse compared to patients with EOT PR (2-year OS 50%) or early relapse (2-year OS 58%)(P = 0.001)(Figure 1A). In patients with early relapse, the 2-year OS was not significantly different among those who relapsed within 3 months or between 3 and 6 months but appeared better for those relapsing between 6 and 12 months (Figure 1B). Our findings validate the results in our previously reported Mayo cohort, other than the survival improvement in early relapsing patients between 6 and 12 months in LEO. Keyword: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. Y. Wang Employment or leadership position: Merck - immediate family member Consultant or advisory role: Loxo; Incyte; Innocare; TG Therapeutics; Kite, A Gilead Company; Lilly; Janssen; BeiGene Stock ownership: Merck - immediate family member Honoraria: Kite, A Gilead Company Research funding: InnoCare; Incyte; Novartis; Genentech; Loxo; MorphoSys; Genmab M. J. Maurer Employment or leadership position: Exact Sciences - immediate family member Consultant or advisory role: Genmab; Adpative Biotechnologies Stock ownership: Exact sciences - immediate family member Research funding: MorphoSys; Bristol Myers Squibb; roche/Genentech; Genmab S. Ayyappan Consultant or advisory role: TG Therapeutics, Seattle Genetics, BeiGene, Intellisphere LLC, Fate Therapeutics, AstraZeneca Pharmaceuticals, Abbvie Research funding: Genmab, Regeneron, Genentech T. M. Habermann Consultant or advisory role: Celgene; Kite/Gilead Research funding: Genentech Other remuneration: Uncompensated: Tess Therapeutics; Loxo/Lilly; MorphoSys; Incyte; BeiGene J. R. Cerhan Consultant or advisory role: Bristol-Meyers-Squibb; Protagonist Therapeutics Research funding: NanoString Technologies; Celgene; Genentech; Genmab; Other remuneration: Uncompensated: Regeneron G. S. Nowakowski Consultant or advisory role: Celgene; MorphoSys; Genentech; Selvita; Debiopharm Group; Kite/Gilead; TG Therapeutics; Kymera; Karyopharm Therapeutics; Ryvu Therapeutics; Bantham Research funding: Celgene; NanoString Technologies; MorphoSys

A single‐center experience of low‐dose radiotherapy for primary extranodal marginal zone lymphoma of bronchus‐associated lymphoid tissue (BALT)

Introduction: Extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue (BALT) is a rare cancer for which optimal treatment strategies are not well defined. Retrospective analyses show equivalent or superior outcomes with surgical resection compared to systemic therapy or active surveillance. Despite a well established role for radiotherapy in the management of other types of extranodal marginal zone lymphoma (MZL), its role in BALT lymphoma is underexplored. Methods: We screened 153 patients with a diagnosis of primary BALT lymphoma treated at a single institution from 1995 to 2022. Inclusion criteria comprised patients aged 18 years or older, histologically confirmed BALT lymphoma, and receipt of radiotherapy at initial presentation or disease progression/recurrence. We excluded patients with synchronous evidence of lymphoma involving non-thoracic extranodal sites and/or lymphadenopathy outside of the mediastinum and hilum, as these patients might represent MZL with secondary lung involvement as opposed to primary BALT lymphoma. All patients underwent baseline PET/CT staging. We extracted patient, tumor, imaging, and treatment characteristics from the electronic medical record. We defined active surveillance as at least 3 months of follow up prior to initiating active therapy combined with documentation of this plan in the medical record. We assessed treatment response using the RECIL 2017 criteria. Results: We report the largest to date single-center retrospective analysis of 13 patients (median age 67 years, range 33–84 years) with localized BALT lymphoma treated with radiotherapy. The median tumor size was 3.6 cm (range 0.8–8.2 cm) with a median SUV of 3.9 (range 1.3–11.4). Most patients (n = 8, 62%) received radiotherapy for BALT lymphoma after failing first-line treatment, including active surveillance (n = 3), surgical resection (n = 2), or systemic therapy (n = 3). Of 15 irradiated lesions, most (n = 10, 67%) received very low-dose radiotherapy (VLRDT) of 4 Gy (range 4–36 Gy). With a median follow-up of >50 months, only 3 patients experienced progression of disease, none within the irradiated field (1 following VLDRT and 2 following full-dose RT). Among all treated lesions, the overall response rate was 100% (n = 5, 33% partial response [PR] and n = 10, 67% complete response [CR]). Among 10 lesions treated with VLDRT, 6 (60%) achieved CR; among 5 lesions treated with full-dose RT, 4 (80%) achieved CR. There were no events of secondary lung cancers within or in proximity to the irradiated field. Conclusions: Radiotherapy, including VLDRT, is a feasible, well tolerated, non-invasive and effective treatment strategy for primary BALT lymphoma that can be considered in both the upfront and recurrent treatment settings. The research was funded by: National Cancer Institute (P30 CA008748) Keywords: Extranodal non-Hodgkin lymphoma, Indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.