Secondary Lymphoma Research Articles

EPID-13. PREDICTORS OF HISTOPATHOLOGIC RESULTS OF BRAIN BIOPSY IN PATIENTS SUSPECTED OF SECONDARY CNS LYMPHOMA

Abstract Patients suspected of secondary CNS lymphoma (SCNSL) often undergo brain biopsies. Recent studies doubt biopsy utility due to high SCNSL diagnosis rates. We sought to enumerate histopathologic biopsy results in suspected SCNSL patients to evaluate utility of biopsy. We furthermore assess clinical and radiographic factors based on ability to distinguishing SCNSL from non-SCNSL. 109 patients with non-CNS lymphoma who subsequently presented with brain lesions that underwent biopsy at MD Anderson Cancer Center were included. Histopathologic diagnoses were obtained. Pre-operative imaging was assessed for contemporary radiologic diagnoses by obtaining the leading differential reported at the time of the study. Subsequently, a staff neuroradiologist, blinded to biopsy outcomes and clinical considerations, provided a retrospective diagnosis. 61 patients had SCNSL whereas 48 did not. Non-SCNSL biopsy results included infection (n=16, 33%), glioma (n=12, 25%), nonspecific (n=12, 25%), and other metastases (n=3, 6%). Patients with non-indolent lymphoma (DLBCL, mantle cell, Burkitt’s, and lymphoblastic lymphoma) were more likely to have SCNSL on biopsy (p<0.001, OR 12.55). Patients with SCNSL had shorter time interval since initial diagnosis (median 18.1mo vs. 63.2mo, p=0.008). Systemic progression of disease at biopsy was not associated with SCNSL (p=0.35). There was no difference in age, stage, LDH, Albumin, ECOG, IPI, anatomic location, or B-symptoms at times of diagnosis or neurosurgery. No patient had positive CSF cytology prior to biopsy. Neither retrospective nor contemporary radiographic diagnoses had sufficient accuracy to replace biopsy. A positive retrospective diagnosis trended towards association with SCNSL pathology (sensitivity=0.94, specificity=0.23, PPV=0.65, NPV=0.70, p=0.08). A positive contemporary diagnosis was associated with SCNSL pathology (sensitivity=0.67, specificity=0.73, PPV=0.76, NPV=0.64, p<0.001). Similar biopsy proportions yielded SCNSL and non-SCNSL. Although some factors are associated with SCNSL, none can reliably distinguish patients. Given the divergent treatments for the reported pathologies, our study reiterates the necessity of biopsy in suspected SCNSL.

Clinical outcomes of chimeric antigen receptor T-cell therapy following autologous hematopoietic stem cell transplantation in 38 patients with refractory/relapsed primary or secondary central nervous system lymphoma.

Several reports have indicated that chimeric antigen receptor (CAR) T-cell therapy following autologous hematopoietic stem cell transplantation (ASCT) is a promising strategy for refractory/relapsed (r/r) central nervous system lymphoma (CNSL), but the number of reported cases is limited. The cohort in this retrospective study consisted of 38 patients with r/r CNSL who received CAR T-cell therapy following ASCT at our center between January 2019 and April 2024. Group comparisons of continuous variables were tested using the unpaired Student's t-test or the Mann-Whitney U-test, while categorical variables were analyzed using Fisher's exact test. The Kaplan-Meier method was employed to estimate survival curves, and group comparisons were performed using the log-rank test. The cohort comprised 38 patients with r/r CNSL, all of whom had active CNS involvement. After therapy, the best overall response rate (ORR) of all patients was 78.9%. Subgroup analysis found that a lower ORR was observed in patients with lactate dehydrogenase levels above the upper limit of normal (60.0% vs. 91.3%, P = 0.039). With a median follow-up of 37.5months, the estimated 1-year overall survival (OS) and progression-free survival (PFS) rates were 72.8% and 57.4%, respectively. The risk factors associated with PFS was no response to current therapy (adjusted hazard ratio: 22.87, P < 0.001). The incidence rates of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were both 13.2%. Among the 25 patients with secondary CNSL (SCNSL), the best ORRs were 91.7% for those with CNS lesions only and 61.5% for those with CNS and systemic lesions (P = 0.160), while the estimated 1-year PFS rates were 83.3% and 38.5%, respectively (P = 0.030). CAR T-cell therapy following ASCT shows promising efficacy for r/r CNSL patients. Besides, SCNSL patients with CNS and systemic lesions have inferior treatment efficacy compared to those with CNS lesions only.

Breast metastasis from large cell neuroendocrine carcinoma of the lung: a case report

Abstract Background Primary breast carcinoma is far more common than breast metastases. Common breast metastases usually come from lymphoma, leukemia, melanoma, and ovarian cancers. Breast metastases from neuroendocrine carcinomas are considered an exceeding rare entity. It has been reported in the literature that the pathological presentation of this particular metastatic tumor is very challenging as it shares many morphological characteristics with primary breast carcinoma. Case presentation We report a case of a patient with large cell neuroendocrine carcinoma of the lung metastasizes to both breasts. The patient was initially presented with brain metastasis of unknown origin. Further radiological imaging workup showed multiple bilateral breast masses and bilateral lymphadenopathy, which raised concern for secondary lymphoma of the breast. The histopathology of this case was challenging, particularly when triple negative invasive ductal carcinoma diagnosis had been made. Multidisciplinary meetings between medical oncologists, radiologists, and pathologists profoundly helped confirming the diagnosis of metastatic large cell neuroendocrine tumor to the breast. Conclusion Large cell neuroendocrine carcinoma of the lung is a relatively uncommon diagnosis with generally poor prognosis. Large cell neuroendocrine carcinoma that metastasizes to the breast is even scarcer. Correlation between clinical assessment, radiological imaging, and pathological evaluation is the key in making such an unusual and complex diagnosis. Additionally, radiologists should be aware of metastatic presentations of the breast and avoid confusion with mimicking benign entities or primary breast carcinomas.

CAR T-cell Therapy for Central Nervous System Lymphoma.

While anti-CD19 CAR T-cell therapy represents a major advance in systemic diffuse large B-cell lymphomas, central nervous system (CNS) lymphomas have been excluded from pivotal trials because of the fear of neurotoxicity. The purpose of this review was to assess the efficacy and tolerance of CAR T-cells in CNS lymphomas based on recently published studies. All the studies on CAR T-cell therapy for both primary and secondary CNS lymphomas reported high response rates (complete response rates ranging from 32 to 67%) in highly pre-treated patients. One-year PFS reached 40 to 60% in several studies. Neurotoxicity occurred in 36 to 68% of patients, including grade 3-4 neurotoxicity in 4.5 to 29% of patients. CAR T-cell therapy appears to be a very promising treatment in CNS lymphomas, with efficacy results close to those observed in systemic lymphomas. The toxicity profile, notably regarding neurotoxicity, is reassuring and should not prevent the development of CAR T-cells in the disease.

Frequency of secondary T-cell lymphoma in chimeric antigen receptor Tcell naïve B-cell lymphoid-lineage cancers is higher than that reported on chimeric antigen receptor T-cell therapy.

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RE-VISITING BIOPSIES FOR SUSPECTED CNS LYMPHOMAS: TO BIOPSY OR NOT TO BIOPSY?

Abstract AIMS It is a common practice to get a histological diagnosis before treatment of suspected CNS (central nervous system) lymphoma. Should CNS lesions be routinely biopsied in patients with background systemic lymphoma? METHOD A 10-year retrospective review of biopsy-proven CNS lymphoma was conducted. Data was analyzed using SPSS for Windows, version 25 (SPSS, Inc., Chicago, Illinois, USA), and a p-value &amp;lt; 0.05 was considered significant for the appropriate test statistic. RESULTS Patients with background systemic lymphoma whose brain MRI appearances were in favour of lymphoma after MDT discussion all had histologically-proven lymphoma after brain biopsy. Pre-biopsy MDT diagnosis was congruent with post-biopsy histology in 87.6% of cranial lesions (p-value 0.003) and 40% of spinal lymphomas (p-value 0.002). Secondary CNS lymphoma was seen in 21.2%. Stereotactic brain biopsy was the most common biopsy technique for cranial lesions (79.8%). Histology was Diffuse B Cell Lymphoma in 93% of cases. The mean Ki67 percentage for cranial lymphomas was higher than that of spine (p-value 0.028) The complication rate for cranial biopsy was 8.9%. Transient motor deficits (4.4%) and post-operative haematoma (2.2%) were the most common. The 24-hour post-brain biopsy mortality rate was 1.1%, while overall 30-day post-op mortality rate was 4.4%. The mean percentage of Ki67 was higher among patients who had complications (p-value 0.001). CONCLUSION In a setting of properly constituted neurooncology MDT, a sub-set of patients with suspected brain lymphoma and background systemic lymphoma might not require brain biopsy. KEY WORDS Lymphoma, Brain, Spine, Biopsy, Complication

Analysis of Therapeutic Efficacy and Adverse Prognostic Factors of Secondary Central Nervous System Lymphoma

To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma (SCNSL). Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected. A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival. Multivariate logistic regression analysis was used to explore the adverse prognostic factors. Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research. Their 2-year overall survival (OS) rate was 46.01% and median survival time was 18.1 months. The 2-year OS rates of HD-MTX group and TMZ group were 34.3% and 61%, median survival time were 8.7 and 38.3 months, and median progression-free survival time were 8.1 and 47 months, respectively. Multivariate logistic regression analysis showed that age, sex, IPI, Ann Arbor stage were correlated with patient survival time. The median survival time of patients with CD79B, KMT2D, CXCR4, ERBB2, TBL1XR1, BTG2, MYC, MYD88, and PIM1 mutations was 8.2 months, which was lower than the overall level. HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.

MO59-1 An investigator-initiated phase II trial of tirabrutinib in patients with relapsed or refractory secondary CNS lymphoma

MO59-1 An investigator-initiated phase II trial of tirabrutinib in patients with relapsed or refractory secondary CNS lymphoma

Treatment of refractory diffuse large B-cell lymphoma involving the central nervous system with polatuzumab vedotin-based regimen: a case report and literature review

Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b, which has been shown to be effective in treating newly diagnosed and relapsed/refractory diffuse large B cell lymphoma (DLBCL) during clinical trials. This study aims to conduct a retrospective analysis of the clinical characteristics, diagnosis, and treatment of a patient with refractory secondary central nervous system lymphoma at Beijing Hospital, alongside a review of relevant literature. This study included a 79-year-old female patient who was diagnosed with DLBCL affecting the ilium, sacrum, spinal cord, and nerve roots and had an IPI score of 5 and a high-risk score according to MSKCC. She showed a geriatric comprehensive assessment (IACA) score of 2, which was categorized under the unfit group. Her initial treatment comprised chemo-free therapy and radiotherapy, followed by progression. In the second-line treatment, a Pola-based regimen was applied, and the patient achieved a complete response, suggesting that this regimen may be a therapeutic option for patients with DLBCL involving the central nervous system.

A Phase II Study Assessing Long-term Response to Ibrutinib Monotherapy in Recurrent or Refractory CNS Lymphoma.

Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase. We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL). We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined cohort of 46 patients (31 with PCNSL and 15 with SCNSL). Patients received ibrutinib at 560 or 840 mg daily in the dose-escalation cohort and ibrutinib at 840 mg daily in the expansion cohort. The median follow-up was 49.9 and 62.1 months for patients with PCNSL and SCNSL, respectively. We sequenced DNA from available tumor biopsies and cerebrospinal fluid collected before and during ibrutinib therapy. Tumor responses were observed in 23/31 (74%) patients with PCNSL and 9/15 (60%) patients with SCNSL, including 12 complete responses in PCNSL and 7 in SCNSL. The median progression-free survival (PFS) for PCNSL was 4.5 months [95% confidence interval (CI), 2.8-9.2] with 1-year PFS at 23.7% (95% CI, 12.4%-45.1%). The median duration of response in the 23 PCNSL responders was 5.5 months. The median PFS in SCNSL was 5.3 months (95% CI, 1.3-14.5) with a median duration of response of 8.7 months for the 9 responders. Exploratory biomarker analysis suggests that mutations in TBL1XR1 may be associated with a long-term response to ibrutinib in PCNSL (P = 0.0075). Clearance of ctDNA from cerebrospinal fluid was associated with complete and long-term ibrutinib responses. Our study confirms single-agent activity of ibrutinib in r/r CNS lymphoma and identifies molecular determinants of response based on long-term follow-up.

Two-year Outcomes of Ultra-low-dose Radiotherapy in the Treatment of Ocular Adnexal B-cell Lymphomas.

This study focuses on the efficacy and 2-year outcomes of ultra-low-dose radiotherapy (RT) in treating primary and secondary ocular adnexal lymphoma (OAL). A retrospective analysis was conducted on patients with OAL between 2017 and 2022, treated with 4 Gy of RT. The primary and secondary outcomes assessed were response rate, progression-free survival, and lymphoma-related death. Twenty-one patients with primary and secondary OAL of diverse, presentations, subtypes, and stages were included. The orbital tumors had an average size of 17 × 16 × 16 mm. Of the 14 primary OAL cases, 3 (14%) had T1N0M0 disease, 8 (38%) T2N0M0, and 3 (14%) T3N0M0 (AJCC 8th edition staging); of the 7 secondary OALs, 4 (19%) were stage IE, 2 (10%) stage IIE, and 1 (5%) stage IIIE (Ann Arbor staging). Ultra-low-dose RT yielded a 95% complete response rate and 100% progression-free survival rates, both locally and systemically at 2 years. Mild dry eyes were reported in 14% of patients as a late treatment toxicity. Ultra-low-dose RT emerges as an effective and well-tolerated treatment approach for OAL. Our findings support the use of 4 Gy, showcasing high complete response rates (95%) and durable disease control without significant local relapses over an average follow up of 27 months. Our results align with earlier investigations, validating the curative potential of ultra-low-dose RT and reinforcing the concept of achieving favorable outcomes with minimal intervention. This approach may potentially alleviate the burden of long-term ocular side effects associated with higher radiation doses, enhancing the overall quality of life for OAL patients.

Clinical Features and Prognosis of Secondary Intestinal Diffuse Large B-Cell Lymphoma

To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma (SI-DLBCL), in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology. The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted, the clinical and pathological features, diagnosis, treatment and prognosis were analyzed. Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors. Among the 138 patients with SI-DLBCL included in this study, 85 (61.59%) were male, 53 (38.41%) were female, the median age of onset was 59.5 (16-84) years, the clinical manifestations lacked specificity, the first-line treatment regimen was mainly chemotherapy (67.39%), 94 cases (68.12%) received chemotherapy alone, 40 cases (28.98%) were treated with chemotherapy combined with surgery, and 4 cases (2.90%) were treated with surgery alone. The median follow-up time was 72 (1-148) months. Among the 138 patients with SI-DLBCL, 79 (57.25%) survived, 34 (24.64%) died, 25 cases (18.12%) lost to follow-up, the PFS rates of 1-year, 3-year and 5-year were 57.97%, 49.28% and 32.61%, and the OS rates of 1-year, 3-year and 5-year were 60.14%, 54.35% and 34.06%, respectively. The results of univariate Cox regression analysis showed that age, Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients, and age, Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients. The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients. Patients with SI-DLBCL are more common in middle-aged and elderly men, and the early clinical manifestations lack specificity, and the first-line treatment regimen is mainly R-CHOP chemotherapy, and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Secondary Breast Lymphoma: A Case Report and Review of Literature

Secondary Breast Lymphoma: A Case Report and Review of Literature

De novo primary malignant lymphoma of the dura following recurrent episodes of subdural abscess presenting as chronic subdural hematoma: illustrative case.

Chronic inflammation of the thorax, as in tuberculosis-related pyothorax, can cause secondary malignant lymphomas. However, primary malignant lymphoma of the central nervous system, specifically of the dura mater, developing after intracranial infection or inflammation has rarely been reported. Herein, the authors describe a case of primary dural lymphoma that developed secondary to subdural empyema, with an initial presentation mimicking a chronic subdural hematoma. A 51-year-old man had undergone single burr hole drainage for subdural empyema 2 years prior. The patient subsequently underwent multiple craniotomy and drainage procedures, with successful remission of the subdural empyema. He was subsequently referred to the authors' hospital approximately a year after his initial treatment because of a recollection of subdural fluid, which was suspected to be recurrent empyema. After another single burr hole drainage, which revealed only a subdural hematoma, a histopathological diagnosis of B-cell lymphoma of the dural/subdural membrane was made. Subsequent radiation therapy was completed, with good local control and no recurrence of the subdural hematoma confirmed at 2 months posttreatment. Intracranial lymphoma triggered by chronic inflammation is rare but should be considered a differential diagnosis in subdural hematomas for which the background pathology is unclear. https://thejns.org/doi/10.3171/CASE24153.

Nodal T follicular helper cell lymphoma with aberrant CD20 expression and monoclonal TCR, IG rearrangements secondary to Classical Hodgkin Lymphoma: a case report.

Classical Hodgkin Lymphoma (CHL) is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse to other subtypes, with the development of secondary peripheral T-cell lymphoma (PTCL) being relatively uncommon. Herein, we report a rare case of nodal T follicular helper cell lymphomas,nos (nTFHL-NOS) secondary to CHL, accompanied by aberrant CD20 expression and clonal rearrangements of T-cell receptor (TCR) and immunoglobulin (IG). A 74-year-old male, was diagnosed with CHL, leaning toward the mixed cell type, 6years ago. He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66months later. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2cm × 1cm. We discuss this rare case and review related literature.

Optic nerve infiltration as a significant feature in the treatment of a rare secondary intraocular lymphoma derived from a primary breast B-cell lymphoma: A case report

Intraocular lymphoma (IOL) is a rare form of lymphocytic malignancy which may pose a significant diagnostic challenge as it may masquerade various uveitis entities, with secondary IOL being less common than primary IOL. A 47-year-old woman presented with blurring of the right eye and floaters since 5 months before admission. She had a history of complete remission from primary breast diffuse large B cell lymphoma for five consecutive years. Both eyes had vitreous haziness and several yellowish, thickened retinal lesions with edematous and infiltrated optic nerves. The best-corrected visual acuity was hand movement for the right eye and 6/45 for the left eye. Cytopathologic exam of the vitreous showed a B cell origin lymphoma. Cerebral magnetic resonance imaging revealed new parenchymal lesions suggestive of metastatic lesions. The patient was given multiple rituximab intravitreal injections and systemic chemotherapy. Treatment options for IOL might be influenced by the central nervous system (CNS) involvement, which is signified by infiltration of the optic nerve in this case.

Comparative Study on the Clinicopathologic and Molecular Characteristics of Primary and Secondary Diffuse Large B-cell Lymphoma in the Central Nervous System.

Diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive B-cell lymphoma with clinical and molecular heterogeneity. Primary CNS-DLBCL (PCNSL) affects the brain, eyes, leptomeninges, or spinal cord without systemic involvement. Secondary CNS-DLBCL (SCNSL) manifests concurrently with systemic lymphoma or as an isolated CNS relapse with poor prognosis. Next-generation sequencing (NGS) was used to identify genomic alterations in 32 PCNSL and 9 SCNSL cases. Single nucleotide variants and copy number variations in addition to the clinicopathologic data and proposed risk predictive values were compared to aid in diagnostic differentiation between the two types of lymphomas. The MCD genotype, characterized by mutations in MYD88 and CD79B, is the most common alteration in PCNSL and is associated with lower survival rates. The frequency of MYD88 mutation was significantly higher in PCNSL compared to SCNSL (75.0% vs. 33.3%; p=0.042). Recurrent copy number loss of 6p21 occurred in 56.1% of cases, more often in PCNSL (65.6%) than in SCNSL (22.2%) (p=0.028). Diagnostic positive predictive values (PPV) of MYD88 mutation and 6p21 loss for PCNSL were 89% and 91%, respectively. PPV of both alterations was 93% for the diagnosis of PCNSL. MYD88 mutation and 6p21 loss were significantly higher in PCNSL than in SCNSL, and novel risk prediction models based on these distinct genomic profiles can aid in the clinical differentiation of PCNSL and SCNSL.

Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy

BackgroundThe risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.MethodsWe reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.ResultsA total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein–Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques.ConclusionsOur results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.)

A pilot study of axicabtagene ciloleucel (axi-cel) for relapsed/refractory primary and secondary central nervous system lymphoma (PCNSL and SCNSL).

2006 Background: Prognosis of patients with relapsed/refractory (R/R) CNSL is poor with no standard of care treatment options. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) has shown efficacy in R/R systemic large B-cell lymphoma (LBCL) and could be considered for R/R CNSL. Methods: We conducted a pilot study of axi-cel in patients with R/R CNS LBCL. No bridging therapy except corticosteroids was allowed after enrollment. Ommaya reservoir was placed before infusion. Patients underwent lymphodepletion with fludarabine and cyclophosphamide followed by axi-cel dosing of 2x106 cells/kg intravenous infusion. The study enrolled 18 patients, of whom the first 6 patients were observed for treatment-limiting toxicities (TLTs). Primary endpoint was safety, measured by rate of TLTs and grade 3+ adverse events (AEs). Secondary endpoints included objective response rate (ORR), complete response (CR) rate, duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Exploratory analyses include paired peripheral blood (PB) and CSF analyses for axi-cel pharmacokinetics, pharmacodynamics, flow cytometry, single-cell RNA-Seq. Results: We report the results of the entire cohort of 18 patients (13 PCNSL, 4 SCNSL, 1 concurrent systemic &amp; ocular L) enrolled. Median age was 62 years (33-80), 8/18 were women. Median number of prior therapies was 3 (1-7). No TLTs were observed; 16/18 (89%) patients developed cytokine release syndrome/CRS (grade 3+, 0%); 8/18 (44%) developed immune effector cell-associated neurologic syndrome/ICANS, 5/18 (28%) grade 3+. Two patients developed Ommaya-related meningitis requiring explant with recovery. One patient had grade 3 seizures that resolved with anti-epileptic agents. The ORR was 94% (17/18); 67% CR (12/18). The median time to best response was 3 months. As of January 25, 2024, the median follow up was 24.2 months, median DOR 13.4 months and 9 patients had progressed. The median PFS was 14.3 months (95% CI: 6.3-NR) and median OS, 26.4 months (95% CI: 11.2-NR). Seven patients have died, all from disease progression. At the time of presentation, there will be a minimum follow-up of 12 months. Correlative data on all 18 patients will be presented at the meeting. Axi-cel pharmacokinetics in the first 12 CNSL patients was similar to that previously reported for DLBCL patients without CNS involvement in ZUMA-1 and ZUMA-7. Patients with CR demonstrated increased peak levels of pro-inflammatory cytokines. CSF CAR T cells exhibit Type I interferon (IFN) transcriptomic signature compared to proliferative signature in blood. Conclusions: Axi-cel was safe and well-tolerated in CNSL patients with encouraging efficacy and median PFS and durability of response of more than 1 year. There was no apparent additional risk of adverse neurologic events including ICANS from axi-cel. Clinical trial information: NCT04608487 .

Occurrence of Secondary Non-Hodgkin Lymphomas Among Our Classical Hodgkin Lymphoma Patients: A Single-Centre Experience.

Objective Non-Hodgkin lymphoma (NHL) arising as a secondary malignancy in patients treated for classical Hodgkin lymphoma (cHL) is an infrequent and challenging clinical scenario. NHL can be presented synchronously with cHL or may develop later, sequentially, up to years after treatment for cHL. The relationship between the two lymphomas is unclear, and there are no clear guidelines forthe management ofthese patients. We would like to find a better clinical understanding of this issueso this study investigates the occurrence and clinical characteristics of secondary NHL. Materials and methods In this retrospective cohort examination, we collected cHL cases when NHL occurred during or after the course of treating cHL. We performed the histopathologic revisions of the samples, and in every case where the quality of the sample was lower, we performed molecular examinations to find the association between cHL and NHL. We performed next-generation genome sequencing (NGS) and immunoglobulin heavy-chain variable region gene (IgHV) clonality testing. Results In a cohort of 164 cHL patients diagnosed between 2011 and 2020, six patients were identified with NHL during rebiopsy prompted by lymphoma relapse or progression. Among these, five patients were diagnosed with post-germinalcenter-originated diffuse large B-cell lymphoma (post-GC DLBCL), and one patient presented high-grade B-cell lymphoma (HG-BCL). The NHL manifestation differed in its timing: three cases emerged after successful cHL treatment, with at least 18 months of complete remission, while the other three patients faced primary refractory cHL. Notably, the primary refractory cases did not exhibit a confirmed clonal relationship between cHL and NHL, but NGS data raised the possibility of synchronous NHL in one case. In contrast, among the patients with sequentially occurring NHL, polymerase chain reaction (PCR) testing of the IgHV gene affirmed a clonal connection between cHL and secondary DLBCL in one case, while the high morphological similarity suggested a potential clonality between the two lymphomas in another case. Conclusion This study reveals that secondary NHL may manifest both synchronously and sequentially following cHL. Our results suggest that synchronous NHL has a worse prognosis compared to sequentialcaseswhen the different lymphomas are not recognized at the time of diagnosis. As our data showed, in some cases, mutations that accompany the tumor cells throughout their clonal evolution can be identified, with additional mutations later on. In the future, next-generation sequencing (NGS)-based processing of liquid biopsy samples can overcome the limitations resulting from the spatial heterogeneity of lymphoid malignancies. Over the long term, this identification could lead to early patient selection and alternative treatment strategies, ultimately leading to improved prospects for cure.