Extranodal Disease Research Articles

Bridging Radiotherapy Prior to Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphomas: An ILROG Multi-Institutional Study

To report an ILROG multi-institutional analysis of bridging radiotherapy (BRT) prior to CD19-targeting chimeric antigen receptor T-cell (CAR T) therapy for relapsed/refractory aggressive B-cell lymphomas (BCL). Weretrospectively reviewed 115 patients (pts) with diffuse large BCL (n = 101, 88%), primary mediastinal BCL (n = 11, 10%), mantle cell lymphoma (n = 2, 2%), and T-cell/histiocyte rich large BCL (n = 1, 1%) who received BRT prior to commercial CAR T from 2018-2020 across 6 institutions. BRT toxicities were graded per CTCAE v5.0, cytokine release syndrome (CRS) per ASTCT, and immune effector cell-associated neurotoxicity syndrome (ICANS) per either ASTCT or CTCAE v5.0. Progression-free survival (PFS) and overall survival (OS), measured from CAR T infusion, were estimated using the Kaplan-Meier method. PFS was modeled using Cox regression with stepwise variable selection. BRTwas given prior to axicabtagene ciloleucel (axi-cel; n = 82, 71%), tisagenlecleucel (tisa-cel; n = 31, 27%), or brexucabtagene autoleucel (n = 2, 2%). Median age was 62 years with median of two prior lines of therapy. Most pts had advanced stage III/IV disease at leukapheresis (n = 87, 76%), elevated pre-leukapheresis LDH (n = 73, 63%), and bulky disease (n = 55, 50%) (1 lesion ≥7.5 cm). 78 pts (68%) had extranodal disease, 12 (10%) had central nervous system (CNS) involvement, and 36 (31%) had bone involvement. Systemic bridging therapy was given to 42 pts (37%). Median intervals from leukapheresis to BRT start and from BRT completion to CAR T infusion were 5 days (IQR -6, 11) and 12 days (IQR 9, 23), respectively. BRT was delivered to 163 total sites; most commonly the abdomen/pelvis (n = 58, 50%), head/neck (n = 34, 30%), thorax (n = 20, 17%), extremity/soft tissue (n = 20, 17%), and CNS (n = 13, 11%). Median biologically effective dose was 31.3 Gy (IQR 24, 39). Most common regimen was 30 Gy in 10 fractions (n = 27, 17%). 40 pts (35%) received comprehensive BRT (to all active lesions). There were no grade ≥3 BRT toxicities. Grade ≥3 CRS occurred in 9 pts (8%), including 8/82 (10%) after axi-cel and 1/31 (3%) after tisa-cel. Grade ≥3 ICANS occurred in 23 pts (20%), including 22/82 (27%) after axi-cel and 1/31 (3%) after tisa-cel. Median follow up was 26.9 months. 1- and 2-year OS rates were 60% and 49%. 1- and 2-year PFS rates were 41% and 35%. Comprehensive BRT associated with superior PFS (HR 0.34, 95% CI 0.19-0.62, p<0.001) in a multivariable model with age ≥60, ECOG ≥2, advanced stage, CNS disease, pre-leukapheresis LDH, and axi-cel. In this multi-institutional study, pts receiving BRT prior to CAR T therapy for BCL frequently had bulky disease yet experienced favorable PFS and OS. There were no serious toxicities attributable to BRT, and the rates of CRS and ICANS are comparable to those after CAR T alone. Comprehensive BRT associated with superior PFS.

Consolidative Radio therapy in Place of Autologous Stem Cell Transplant in Patients with Low-Risk Relapsed/Refractory (R/R) Classic Hodgkin Lymphoma (cHL) Treated with Nivolumab plus Brentuximab Vedotin: CheckMate 744

Standard of care treatment for patients with relapsed and refractory classic Hodgkin lymphoma (RRHL) involves second line therapy followed by high dose therapy and autologous stem cell transplant (HDT/ASCT) and carries with it significant costs and toxicities to the patient. Some patients with RRHL may not require such intensive therapy, especially in the era of targeted chemotherapy and checkpoint inhibitors. CheckMate 744 (NCT02927769) evaluated a novel second-line therapy that omits HDT/ASCT by combining brentuximab vedotin (BV) and a nivolumab (N) followed by consolidative ISRT for low risk RRHL. Pts were aged 5-30 y and had one prior treatment without HDT/ASCT. Low-risk RRHL were those at relapse without B symptoms or extranodal disease, limited sites of relapse (≤4 sites of disease above the diaphragm or ≤3 sites above/below the diaphragm) AND with initial Stage IA, IIA with relapse <1 year if they received ≤3 cycles of chemotherapy and no RT OR Stage IA/B, IIA/B, IIIA ≥ 1 year. Patients received 4 cycles of N + BV induction. Patients with complete metabolic response (CMR) received an additional 2 cycles of N + BV before RT consolidation. Patients with suboptimal response received 2 cycles of BV + bendamustine intensification. Those patients achieving CMR proceeded to RT consolidation. RT was delivered to a dose of 30-30.6 Gy at 1.5-1.8 Gy/fraction to an ISRT volume. Among 28 pts treated, the median age (range) was 17 (6-27) years old and 64% of patients were aged < 18 y. Most (79%) pts had stage II disease at diagnosis and 82% had relapsed ≥ 12 months after first line treatment. Of 27 pts continuing in study after induction N + BV, 6 received bendamustine + BV intensification, and 92.9% achieved complete metabolic response. Twenty-two patients received RT consolidation. RT consolidation was delivered using 3D-CRT, IMRT, or proton therapy. After a median (range) follow-up of 31.8 (2.2-55.1) months, the 3-y event-free survival rate and progression-free survival were 86.9% (69.5-94.7%) and 95% (76.7-99%), respectively. A novel combination of N + BV followed by ISRT was an effective second line therapy. This treatment regimen allowed patients to forgo high dose therapy and transplant in favor of consolidative radiotherapy using ISRT. Larger studies challenging the role of high dose therapy and transplant are needed for RRHL.

Outcomes of Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Large B-Cell Lymphoma (LBCL): A Single-Institution Experience.

Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We describe the real-world baseline characteristics, efficacy, safety, and post-relapse outcomes of adult patients with R/R LBCL who received CAR T-cell therapy at the University of California San Diego. A total of 66 patients with LBCL were treated with tisagenlecleucel or axicabtagene ciloleucel. The median age was 59.5, and 21% were over 70 years old. Additionally, 20% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Cytokine release syndrome incidence was 88%; immune effector cell-associated neurotoxicity syndrome incidence was 56%. All-grade infection occurred in 48% of patients and in 79% of patients > 70 years old. Complete response (CR) was achieved in 53% and partial response in 14%. Median progression-free survival (PFS) was 10.3 months; median overall survival (OS) was 28.4 months. Patients who relapsed post-CAR T-cell therapy had poor outcomes, with a median OS2 of 4.8 months. Upon multivariate analysis, both ECOG (HR 2.65, 95% CI: 1.30-5.41; p = 0.007) and ≥2 sites of extranodal involvement (HR 2.22, 95% CI: 1.15-4.31; p = 0.018) were significant predictors of PFS. Twenty-six patients were R/R to CAR T-cell therapy; six patients were in remission at the time of data cut off, one of whom received allogeneic transplant. Overall, older patients can safely undergo CAR T-cell therapy, despite the increased risk of all-grade infection. In our cohort, ECOG performance score and ≥2 sites of extranodal disease are significant predictors of PFS.

Outcome and prognostic factors of pediatric patients with Hodgkin lymphoma: a single-center experience

BackgroundHodgkin lymphoma (HL) is a highly curable malignant tumor. Risk-adapted treatment for children with HL aims to maximize survival while minimizing toxicity. The purpose of this study is to evaluate the outcome and prognostic characteristics of Egyptian pediatric HL patients treated at the National Cancer Institute (NCI), Cairo University.MethodsAll newly diagnosed cases of classic HL treated between January 2016 and December 2018 were included in this study.ResultsThe median age at initial presentation was 8 years in 69 eligible individuals, with a male-to-female ratio of 4.7:1. Eighteen percent of patients had an elevated erythrocyte sedimentation rate (ESR) of more than 50, 42% had more than three lymph node (LN) group involvements, 18.8% had bulky disease, 52.2% were at an advanced stage, and 34% had B symptoms. Age > 15 years, B symptoms, > 3 LN group involvement, extra-nodal disease, and advanced stages significantly affected the overall survival rate (OS) (P-values = 0.03, 0.033, 0.008, 0.017, and 0.032). There was no statistically significant difference between patients who got combined modality therapy (CMT) and those who received chemotherapy alone (3-year OS and event-free survival (EFS) were 95.5% and 87.6% vs. 89.9% and 83.3%, P-values of 0.70 and 0.90). Patients with an interim-negative positron emission tomography-computed tomography (PET-CT) had a 3-year OS of 94.7%, compared to 74.1% in patients with an interim-positive PET-CT (P = 0.06), suggesting that rapid early response (RER) is a significant prognostic factor. There was no statistically significant survival difference between patients with a negative interim PET-CT who got CMT and those who received chemotherapy alone (3-year OS and EFS: 100% and 88.2% vs. 95% and 90%; P = 0.35 and 0.70, respectively). Three-year OS was 93.3% and 100%, and EFS was 74.3% and 100% (P = 0.495 and 0.196%) for those who got 15 Gy versus those who received 20 Gy or more, respectively. At the end of the study, the OS and EFS at 3 years for the whole group were 91.9% and 83.6%.ConclusionTreatment with risk- and response-adaptive treatment should be the standard of care for treating pediatric patients with HL.

A Rare Case of Pseudo-Malignant Paranasal Extranodal Rosai-Dorfman Disease.

Rosai-Dorfman disease is a very rare disease characterized by histiocytic accumulation in the head and neck region and lymph node enlargement. We report a rare pseudo-malignant paranasal extranodal Rosai-Dorfman disease. A 69-year-old-man presented nasal bleeding and nasal obstruction. Paranasal mass was detected in the left nasal cavity and computed tomography (CT) findings are the sphenoid sinus, maxillary sinus, and ethmoid sinus were involved with inconstant bone thickening, however, no bone destruction was detected. Magnetic resonance imaging scans show iso-intensity signal in T1-weighed image and T2-weighed image. Positron emission tomography/CT fluorodeoxyglucose (FDG) uptake in posterior ethmoid sinus and sphenoid sinus, bilateral cervical lymph node, clavicle, and sternum. Based on the above results, we considered malignant lymphoma and performed a biopsy. After pathological examination, a diagnosis of Rosai-Dorfman disease was established.

Central Nervous System Relapse in T and NK cell Lymphomas.

T and NK cell lymphomas are relatively rare and heterogeneous forms of non-Hodgkin lymphoma that are associated with high rates of mortality. Central nervous system relapse carries significant morbidity, though management is largely extrapolated from literature in B cell neoplasms. As such, outcomes for central nervous system involvement in T/NK cell lymphomas are dismal with no standard of care. In this review, we discuss the epidemiology of central nervous system relapse in T/NK cell lymphomas and critically analyze available literature regarding prophylaxis and treatment. Retrospective studies of central nervous system involvement in T/NK cell lymphomas have been limited by small sample sizes and heterogeneity of subtypes, though sites of extranodal involvement and disease subtypes are consistently reported as risk factors. Compelling evidence for the use of central nervous system-directed prophylactic therapy has not yet been established, though recent reports of central nervous system activity with novel agents may suggest promising therapeutic options. The overall rarity of T and NK cell lymphomas has precluded adequate study of prophylaxis and treatment of central nervous system relapse. Collaborative efforts are needed to better define strategies to address CNS disease in T/NK cell lymphomas. These should involve the use of targeted agents, which may hold an advantage over traditional cytotoxic drugs.

Prediction of regional lymph node metastasis in intrahepatic cholangiocarcinoma: it’s not all about size

ObjectivesLymph node metastases (LNM) are frequent in patients with intrahepatic cholangiocarcinoma (iCC) and worsen their prognosis even after surgery. Our aim was to investigate the predictive value of lymph node (LN) short axis, the most common discriminator for identifying LNM in tumor-imaging and to develop a predictive model for regional LNM in iCC taking computed tomography (CT) features of extranodal disease into account.Materials and methodsWe enrolled 102 patients with pathologically proven iCC who underwent CT prior to hepatic resection and hilar lymph node dissection (LND) from 2005 to 2021. Two blinded radiologists assessed various imaging characteristics and LN diameters, which were analyzed by bivariate and multivariate logistic regression to develop a prediction model for LNM.ResultsPrevalence of LNM was high (42.4 %) and estimated survival was shorter in LN-positive patients (p = 0.07). An LN short axis diameter of ≥ 9 mm demonstrated the highest predictive power for LNM. Three additional, statistically significant imaging features, presence of intrahepatic metastasis (p = 0.003), hilar tumor infiltration (p = 0.003), and tumor growth along the liver capsule (p = 0.004), were integrated into a prediction model, which substantially outperformed use of LN axis alone in ROC analysis (AUC 0.856 vs 0.701).ConclusionsLN diameter alone proved to be a relevant but unreliable imaging-marker for LNM prediction in iCC. Our proposed prognostic model, which additionally considers intrahepatic metastases and hilar and capsular infiltration, significantly improves discriminatory power. Hilar and capsular involvement might indicate direct tumor extension to lymphatic liver structures.

TREATMENT STRATEGIES AND PROGNOSTIC FACTORS FOR THE OUTCOME OF PATIENTS WITH HODGKIN LYMPHOMA EXPERIENCING VERY LATE RELAPSES AFTER CHEMOTHERAPY ± RADIOTHERAPY

Background: Despite the excellent long-term outcome of patients with Hodgkin Lymphoma (HL), some cases will be primary refractory or will eventually relapse, mainly within the first 2 years from diagnosis. Patients with sustained complete remission (CR) for ≥5 years are generally considered “cured”. However, Very Late Relapses (VLRs), occurring ≥5 years after treatment initiation, are a non-negligible event and possibly comprise a distinct entity with unique characteristics. Aim: The aim of the current study is to describe the treatment strategies adopted for patients with VLRs as well as their outcome and relevant prognostic factors. Patients/Methods: Patients with HL who experienced VLRs ≥5 years after treatment Initiation with chemotherapy ± radiotherapy (CT±RT), were identified retrospectively from the databases of 8 referral centers. Statistical endpoints were the estimation of time to second failure (TT2F) and Overall Survival after failure (O2S). Results: 145 patients with VLRs were identified. The median age was 49 years (19–82), 69% were males and 18% were ≥65 years old. In 23% of the patients, relapse occurred >15 years after the initial diagnosis. Reinduction with the same regimen was given in 24% of the cases, and 26% were indented to proceeded to high-dose therapy and autologous stem cell transplantation (HDT/ASCT). The 5- and 10-year TT2F were 57% and 53% and the 10-year and 15-year O2S were 59% and 46% respectively. Among 52 deaths, only 28 were disease-related whereas others were attributed to secondary malignancies or unrelated causes. Re-induction with the same regimen did not significantly affect TTF2 and O2S. Despite the numerical difference regarding 5-year FF2P for patients <65 years old who received HDT/ASCT, this was not statistical significant and there was no difference at 10 years. In multivariate analysis B-symptoms, extranodal disease, age ≥65 at relapse, and occurrence of relapse <15 years from diagnosis were independent adverse prognostic factors for TT2F (p = 0.03, 0.003, 0.005 and 0.006 respectively). Anemia, age ≥ 65 and extranodal disease at relapse were also associated with impaired O2S (p = 0.02, <0.001 and 0.044 respectively). We assigned one point to each of the aforementioned unfavorable factors and constructed prognostic scores. Patients combining 2–3 adverse characteristics had significantly compromised outcomes. None of the patients survived at 10-years with the 10-year disease-free-survival being only 36%. Conclusion: The prognosis of VLRs does not appear very favorable, however a considerable proportion of patients were ≥65 years old at the time of relapse when treatment options are limited and also, many patients succumb to disease-unrelated causes. Treatment approaches were heterogenous. In our study B-symptoms, extranodal disease and age ≥65 at relapse were the most important prognostic factors for the outcome of patients with VLRs. Keyword: Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Epidemiologic characteristics, treatment patterns, and survival analysis of plasmablastic lymphoma in the US.

7570 Background: Plasmablastic Lymphoma (PBL) is a rare aggressive subtype of diffuse large B-cell lymphoma primarily affecting the immunocompromised, including those living with HIV. There is no established standard of care, and current survival estimates range from 8-15 months (mos). With the largest previous study of PBL limited to 590 patients (pts), we aimed to evaluate epidemiologic characteristics, treatment patterns and survival trends on a national scale. Methods: Pts diagnosed with PBL from 2010-2020 were identified in the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program. Age-adjusted incidence rates (IR) were calculated using SEER. Demographic and treatment characteristics and overall survival were evaluated in the NCDB using Kaplan-Meier and multivariate Cox regression analysis. Results: For the 1,153 pts identified in SEER, the incidence of PBL was 0.07 per 100,000 person-years, with higher IR in males (0.12) and pts age &gt; 75 years (0.23). IR increased on average by 4.2% per year from 2010 to 2020 (95% CI 1.51-6.96). Of the 1,822 PBL pts in NCDB, the median age at diagnosis was 57 years. PBL was more common in male (77.2%) and White pts (76.8%). Most pts presented at an advanced (III or IV) Ann Arbor stage (59.9%). Pts were HIV+ in 50.2% of cases and 51.2% had extranodal disease. The median OS (mOS) was 22.4 mos (95% CI 16.2-28.6), with a 1-, 5-, and 10-yr OS of 56%, 40%, 32%, respectively. PBL pts treated with multiagent chemotherapy (N = 862, 66%) had mOS of 58.6 mos (95% CI 43.0-74.3). Pts who received no systemic treatment (N = 456, 25%) had mOS of 1.9 mos (95% CI 1.2-2.5). Pts with Stage I disease had a mOS of 86.2 mos, Stage II of 51.1 mos, Stage III of 35.9 mos, and Stage IV of 8.8 mos. Pts with HIV had a greater mOS (44.0 mos [95% CI 28.7-59.3]) than HIV- pts (21.7 mos [95% CI 12.4-30.9]). On multivariate Cox regression adjusted for age, race, and socioeconomic status, factors associated with worse OS included age (HR 1.03 [95% CI 1.02-1.04], p &lt; 0.001), B symptoms (HR 1.35 [95% CI 1.11-1.65], p = 0.003) and advancing stage. Factors associated with improved OS included Hispanic ethnicity (HR 0.70 [95% CI 0.52-0.93], p = 0.014) and extranodal disease (HR 0.77 [95% CI 0.63-0.93], p = 0.001). HIV+ status had no significant impact on survival (HR 1.09 [95% CI 0.87-1.38], p = 0.443). Conclusions: We present the largest study to date describing the epidemiologic, survival, and treatment patterns of PBL. In contrast to prior studies, we found a longer mOS of 58.6 mos among those treated. This may represent a large real-world population providing more accurate estimates or reflect improved outcomes from a growing number of novel therapeutic options. Notably, HIV+ status did not have a significant impact on OS. While OS remains poor, advances in treatment over the last decade are promising and highlight the need for clinical advances to improve front line therapeutic options for PBL.

Treatment outcomes of Limited Stage Grade 3A Follicular Lymphoma

Introduction: While radiotherapy is an established standard of care for limited stage, low grade follicular lymphoma (FL), the management of localized FL grade 3A (FL3A) disease remains controversial. We reviewed the outcomes of grade 3A patients treated with definitive RT, combined modality therapy (CMT), or systemic therapy (ST) alone. Methods: We retrospectively analyzed a single institution database to identify newly-diagnosed, grade FL3A patients with Ann Arbor stage I/II disease treated between 2000 and 2021. Patients were stratified by definitive treatment modality including RT monotherapy, CMT, or ST. Best post-RT imaging response was evaluated using Lugano criteria for all by CT, and by PET if available. Rate of complete response (CR) was compared between the three treatment modalities. Progression-free survival (PFS) and Overall survival (OS) were calculated using Kaplan Meier from first day of treatment. Univariable Cox regression was used to assess possible clinicodemographic associations with PFS. Results: 84 patients (median age 62, 38% male) were analyzed with median follow-up of 6.9 years from initiation of treatment. Patients were stage I (73%) or II (27%) and 92% were initially PET staged at diagnosis. 29 (35%) had extranodal disease. The median (IQR) maximum SUV and size prior to treatment were 9.8 (5.4, 14.0) and 3.2 (2.0, 4.5) cm respectively. RT was the most common treatment modality (n = 48, 57%), followed by CMT (n = 21, 25%), then ST (n = 15, 18%). For RT/CMT patients the planned RT dose was most commonly 36 Gy (32%, range 4–40 Gy). 2 patients (3%) received very low dose of 4 Gy. Of the CMT/ST patients the most common regimen was 3–4 cycles of R-CHOP (53%). 3 patients (8%) received Rituximab alone. Compared to RT patients, ST patients were most likely to have been diagnosed after 2010 (p = 0.002) and have stage II disease (p < 0.001), while CMT patients were more likely to be female (p = 0.03) and have grade 3 disease not further characterized (p = 0.002). The rates of CR post-treatment were 88% for RT, 100% for CMT, and 87% for ST. Factors significantly associated with PFS univariably included the treatment modality (CMT vs. RT HR 0.30, 95% CI: 0.10–0.91, p = 0.03), and presence of low-grade FL component in the biopsy (HR 3.33, 95% CI: 1.43–7.78, p = 0.005). Age, sex, stage, extranodal status, Ki67 score, size, and SUV were not predictive of PFS. The probability of transformation to DLBCL was 4.2% (95% CI: 1.1%–11%) at 5 years after treatment. Overall survival was excellent for all treatment modalities with median OS of 18 years for CMT, and not reached for RT or ST. Keywords: Combination Therapies, Indolent non-Hodgkin lymphoma, Radiation Therapy Conflicts of interests pertinent to the abstract. A. Zelenetz Consultant or advisory role: ADC Therapeutics, AbbVie, Adaptive Biotechnologies Corp Arvinas, Inc. AstraZeneca BeiGene, Ltd. Bristol-Myers Squibb, Curio Science LLC, Dava Oncology, Genentech, Instituto de Ciencias Integradas, Kyowa Kirin Co., Ltd. MEI Pharma, Inc., Medscape, Oncopeptides, AB Sandoz, Inc., Secura Bio, Inc., Suzhou Liang Yihui Network Science and Technology Company, Limited G. Salles Consultant or advisory role: AbbVie, Aptitude Health, Bayer, BeiGene, Ltd., Bio Ascend, Bristol-Myers Squibb, Celgene, Epizyme, Everest Clinical Research Corporation, GenMab, Genentech, Gilead Pharmaceutical, Incyte, Ipsen, Janssen Pharmaceutical, Nordic Nanovector ASA, s, Inc., Loxo Oncology, Miltenyi Biotec Incorporated, MorphoSys AG, Novartis, Owkin, Inc., Physicians' Education Resource, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Roche, Scientific Education Support Ltd., Takeda Millennium J. Yahalom Consultant or advisory role: Convergent R.N.R Ltd. B. Imber Consultant or advisory role: GT Medical Technologies, Inc.

Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: a population-based study

Mental health disorders can potentially decrease quality of life and survival in patients with cancer. Little is known about the survival implications of mental health disorders in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the effect of pre-existing depression, anxiety, or both on survival in a US cohort of older patients with DLBCL. Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients aged 67 years or older, diagnosed with DLBCL in the USA between Jan 1, 2001, and Dec 31, 2013. We used billing claims to identify patients with pre-existing depression, anxiety, or both before their DLBCL diagnosis. We compared 5-year overall survival and lymphoma-specific survival between these patients and those without pre-existing depression, anxiety, or both using Cox proportional analyses, adjusting for sociodemographic and clinical characteristics, including DLBCL stage, extranodal disease, and B symptoms. Among 13 244 patients with DLBCL, 2094 (15·8%) had depression, anxiety, or both disorders; 6988 (52·8%) were female, and 12 468 (94·1%) were White. The median follow-up for the cohort was 2·0 years (IQR 0·4-6·9 years). 5-year overall survival was 27·0% (95% CI 25·1-28·9) for patients with these mental health disorders versus 37·4% (36·5-38·3) for those with no mental health disorder (hazard ratio [HR] 1·37, 95% CI 1·29-1·44). Although survival differences between mental health disorders were modest, those with depression alone had the worst survival compared with no mental health disorder (HR 1·37, 95% CI 1·28-1·47), followed by those with depression and anxiety (1·23, 1·08-1·41), and then anxiety alone (1·17, 1·06-1·29). Individuals with these pre-existing mental health disorders also had lower 5-year lymphoma-specific survival, with depression conferring the greatest effect (1·37, 1·26-1·49) followed by those with depression and anxiety (1·25, 1·07-1·47) and then anxiety alone (1·16, 1·03-1·31). Pre-existing depression, anxiety, or both disorders present within 24 months before DLBCL diagnosis, worsens prognosis for patients with DLBCL. Our data underscore the need for universal and systematic mental health screening for this population, as mental health disorders are manageable, and improvements in this prevalent comorbidity might affect lymphoma-specific survival and overall survival. American Society of Hematology, National Cancer Institute, Alan J Hirschfield Award.

CHARACTERISTICS AND TREATMENT OUTCOMES OF AGGRESSIVE HIGH GRADE B CELL LYMPHOMA WITH MYC AND BCL 6 REARRANGEMENTS

According to the International Consensus Classification of Lymphomas (Blood 2022: 140: 1229–53), a new provisional entity high grade B cell lymphoma with MYC and BCL 6 rearrangements (HGBCL-DH-BCL6) was introduced. HGBCL-DH-BCL6 occurred very rare, in less than 10% of patients with HGBCL with rearrangements. Here we assessed clinicopathological features and treatment outcomes of HGBCL-DH-BCL6. We retrospectively collected clinic-pathological data of patients with HGBCL with MYC/BLC6-rearrangements. All cases were evaluated by histopathological/immunohistochemical/flow-cytometry examination (IHC/FCM), with a broad panel of antibodies, including CD10/CD38/ MYC/LMO2/ BCL2/BCL6. Gene status (MYC/BCL2/BCL6) was examined using fluorescence in situ hybridization (FISH), karyotype was successfully achieved in 70% of patients. We identified 18 patients with MYC-rearrangement (median MYC-R: 49% of examined cells; range: 5%–93%), and BCL6-rearrangements (median BCL6-R: 50% of examined cells; range: 5%–93%) with no BCL2- rearrangements was found. Expression of MYC-protein was found only in 22% of patients. Eleven and seven patients, respectively, had DLBCL and BCL-u morphology. Median age at diagnosis was 57 years (range: 18–84). Advanced stage, extranodal disease, increased dehydrogenase lactate were found in 78%, 33%, 83% of patients, respectively. Only 15 patients received immunochemotherapy: 8 were treated with R-CHOP and CNS prophylaxis, other 7 patients had more intensive therapy: GMALL, CODOX/IVAC or DAEPOCH-R. Six patients had consolidative auto-SCT. Morphology of disease, age and intensity of immunochemotherapy had no impact on response and survival. Only 36% of patients achieved complete remission. Median overall survival (OS) and progression free survival (PFS) were 5.6 months and 3.0 months, respectively. OS and PFS for 1 year were 34% and 28% respectively. Actually, 4 patients are alive with no active disease. HGBCL-DH-BCL6 is a rare and aggressive B-cell lymphoma, often without the IHC-protein MYC deletion, with advanced disease presenting at diagnosis. The outcomes is poor and less than 40% of patient are alive from one year from diagnosis. Intensive therapy has not improved treatment results. Keywords: aggressive B-cell non-Hodgkin lymphoma, pathology and classification of lymphomas No conflicts of interests pertinent to the abstract.

Characteristics and Outcomes of Older Patients With Classical Hodgkin Lymphoma: An Australasian Lymphoma Alliance, and Lymphoma and Related Diseases Registry Study.

There is no standard front-line therapy for older patients with classical Hodgkin lymphoma (cHL). We analyzed the clinical presentation and front-line management of older Australian patients with cHL and explored factors associated with unplanned hospital admission and survival. Patients aged ≥ 61 years and diagnosed between 2011 and 2020, were retrospectively identified through the Lymphoma and Related Diseases Registry (LaRDR) and Australasian Lymphoma Alliance (ALA) institutional databases. Descriptive statistics and Kaplan-Meier survival analyses were performed using STATA-v17. 195 patients were identified, 72 from LaRDR,123 from ALA. Median age of the combined cohort was 72 years (range 61-93); 56.4% male, 35.3% had stage I-II, bulk present in 9.2%, 33.9% had extra-nodal disease and 48.2% had B-symptoms. Chemotherapy was commenced in 91.3% of patients, with an anthracycline-based regimen used in 81%. Median number of cycles given for stage I-II was 2 and for stage III-IV was 6. Radiotherapy was administered in 26.2% of patients. A complete remission to front-line chemotherapy was achieved in 60.7% of patients. During front-line therapy in the ALA cohort, 89 unplanned hospitalizations occurred in 58 patients, with infection accounting for 59.6% of admissions. Treatment-related mortality was 5.2%. Only performance status and anthracycline use correlated with unplanned hospitalizations. Estimated 2-year progression free survival was 63.7% and 2-year overall survival was 71.2%. Anthracycline use and younger age were independently associated with improved survival. The management of older patients with cHL in Australia is diverse but aligns with international data. Anthracycline-based therapy improved survival but resulted in frequent unplanned hospitalizations.

Whole body MRI with Diffusion Weighted Imaging versus 18F-fluorodeoxyglucose-PET/CT in the staging of lymphomas

PurposeTo assess the diagnostic performance of Whole Body (WB)-MRI in comparison with 18F-Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) in lymphoma staging and to assess whether quantitative metabolic parameters from 18F-FDG-PET/CT and Apparent Diffusion Coefficient (ADC) values are related.Materials and methodsWe prospectively enrolled patients with a histologically proven primary nodal lymphoma to undergo 18F-FDG-PET/CT and WB-MRI, both performed within 15 days one from the other, either before starting treatment (baseline) or during treatment (interim). Positive and negative predictive values of WB-MRI for the identification of nodal and extra-nodal disease were measured. The agreement between WB-MRI and 18F-FDG-PET/CT for the identification of lesions and staging was assessed through Cohen's coefficient k and observed agreement. Quantitative parameters of nodal lesions derived from 18F-FDG-PET/CT and WB-MRI (ADC) were measured and the Pearson or Spearman correlation coefficient was used to assess the correlation between them. The specified level of significance was p ≤ 0.05.ResultsAmong the 91 identified patients, 8 refused to participate and 22 met exclusion criteria, thus images from 61 patients (37 men, mean age 30.7 years) were evaluated. The agreement between 18F-FDG-PET/CT and WB-MRI for the identification of nodal and extra-nodal lesions was 0.95 (95% CI 0.92 to 0.98) and 1.00 (95% CI NA), respectively; for staging it was 1.00 (95% CI NA). A strong negative correlation was found between ADCmean and SUVmean of nodal lesions in patients evaluated at baseline (Spearman coefficient rs = − 0.61, p = 0.001).ConclusionWB-MRI has a good diagnostic performance for staging of patients with lymphoma in comparison with 18F-FDG-PET/CT and is a promising technique for the quantitative assessment of disease burden in these patients.

Effect of cumulative dose of brentuximab vedotin maintenance in relapsed/refractory classical Hodgkin lymphoma after autologous stem cell transplant: an analysis of realworld outcomes.

Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL) demonstrated an improved 2-year progression free survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse < 12 months (RL<12) from the end of frontline therapy. Cohort 1 had patients with > 75% of the planned total cumulative dose, cohort 2 with 51 - 75% of dose, and cohort 3 with ≤ 50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL<12, and 39% had END. Forty-four percent of patients had prior exposure to BV and 65% were in complete remission (CR) before ASCT. Only 14% of patients received the full planned BV dose. Sixty-one percent of patients discontinued maintenance early and majority of those (72%) were due to toxicity. The 2-year PFS for the entire population was 80.7%. The 2-year PFS was 89.2% for cohort 1 (n=39), 86.2% for cohort 2 (n=33), and 77.9% for cohort 3 (n=46) (p = 0.70). These data are reassuring for patients who require dose reductions or discontinuation to manage toxicity.

Primary extranodal lymphomas: five-year experience from a tertiary care center of North India.

Primary extranodal lymphomas (pENL) are lymphomas with minimal nodal involvement and dominant extranodal disease. We aimed to study the prevalence and clinicopathological characteristics of pENL presenting at our center over 5 years from January 2015 to January 2020. This is a cross-sectional study of pENL patients in which relevant clinical and laboratory data was collected including demography, site, stage, international prognostic index-revised, imaging findings, hematological, and biochemical parameters and comorbidities including underlying immunodeficiency. The paraffin blocks were subjected to routine hematoxylin and eosin stain and immunohistochemistry with standard lymphoma panel. Of 341 lymphomas, 73 (21.4%) were pENL with commonest site being gastrointestinal tract (31.5%) followed by head and neck (23.2%) and soft tissues (9.6%). Diffuse large B-cell lymphoma (DLBCL) (39.7%) was the commonest histological type (germinal center type-48%, nongerminal center-52%) followed by marginal zone lymphomas (MZL) (23.3%) and primary CNS lymphoma (8.2%). Primary breast lymphoma, primary bone marrow lymphoma, and follicular lymphoma constituted 4.1, 5.4, and 4.1% of pENL, respectively. There was a case of high grade B cell lymphoma of ileum with features intermediate between DLBCL and Burkitt. Other unusual pENL were anaplastic DLBCL of tonsils, DLBCLs of bone marrow with M band, MZL of base of tongue, Richter's transformation of tonsillar small lymphocytic lymphoma, and follicular lymphoma presenting as pericardial mass. Of 12 cases of T-non-Hodgkin lymphoma, commonest were mycosis fungoides (4/12) followed by mediastinal T-lymphoblastic lymphoma (2/12) and peripheral T-cell lymphoma (2/12). pENL has unique clinical presentation depending on the location with site-specific distribution of histological subtypes.

Progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma and B-cell prolymphocytic leukemia: Report from the 2021 SH/EAHP Workshop.

Session 3 of the 2021 Workshop of the Society for Hematopathology/European Association for Haematopathology examined progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and B-cell prolymphocytic leukemia (B-PLL). Thirty-one cases were reviewed by the panel. Additional studies such as immunohistochemistry and molecular genetic testing, including whole-exome sequencing and expression profiling, were performed in select cases. Session 3 included 27 CLL/SLL cases and miscellaneous associated proliferations, 3 cases of B-PLL, and 1 case of small B-cell lymphoma. The criteria for -accelerated CLL/SLL are established for lymph nodes, but extranodal disease can be diagnostically challenging. Richter transformation (RT) is a broad term and includes true transformation from original CLL/SLL clone(s) and clonally unrelated neoplasms. The morphologic, immunophenotypic, and genetic spectrum is diverse with classical and highly unusual examples. T-cell proliferations can also be encountered in CLL/SLL. B-cell prolymphocytic leukemia is a rare, diagnostically challenging disease due to its overlaps with other lymphoid neoplasms. The workshop highlighted complexity of progression and transformation in CLL/SLL and B-PLL, as well as diagnostic caveats accompanying heterogeneous presentations of RT and other manifestations of disease progression. Molecular genetic studies are pivotal for diagnosis and determination of clonal relationship, and to predict response to treatment and identify resistance to targeted therapy.

Improved outcomes for relapsed/refractory Hodgkin lymphoma after autologous transplantation in the era of novel agents

AbstractThe treatment landscape of relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) has evolved significantly over the past decade after the approval of brentuximab vedotin (BV) and the programmed death-1 (PD-1) inhibitors. We evaluated how outcomes and practice patterns have changed for patients with R/R cHL who underwent autologous hematopoietic cell transplantation (AHCT) at our institution from 2011 to 2020 (N = 183) compared with those from 2001 to 2010 (N = 159) and evaluated prognostic factors for progression-free survival (PFS) and overall survival (OS) in both eras. OS was superior in the modern era with a trend toward lower nonrelapse mortality beyond 2 years after transplant. Among patients who progressed after AHCT, 4-year postprogression survival increased from 43.3% to 71.4% in the modern era, reflecting increasing use of BV and the PD-1 inhibitors. In multivariable analysis for patients that underwent transplant in the modern era, age ≥45 years, primary refractory disease, and lack of complete remission pre-AHCT were associated with inferior PFS, whereas receipt of a PD-1 inhibitor-based regimen pre-AHCT was associated with superior PFS. Extranodal disease at relapse was associated with inferior OS. Our study demonstrates improved survival for R/R cHL after AHCT in the modern era attributed to more effective salvage regimens allowing for better disease control pre-AHCT and improved outcomes for patients who progressed after AHCT. Excellent outcomes were observed with PD-1 inhibitor-based salvage regimens pre-AHCT and support a randomized trial evaluating immunotherapy in the second line setting.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study.

Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study.

Extranodal Rosai-Dorfman disease involving pulmonary artery detected by 68Ga-FAPI PET/CT and fused 68Ga-FAPI PET/MRI.

Extranodal Rosai-Dorfman disease involving pulmonary artery detected by 68Ga-FAPI PET/CT and fused 68Ga-FAPI PET/MRI.