Therapy For Lymphoma Research Articles

Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma

Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma

QLTI-03. REAL-WORLD PARADIGM FOR TREATMENT OF PRIMARY CNS LYMPHOMA PATIENTS IN CLINICAL PRACTICE

Abstract Although high-dose methotrexate (HD-MTX) is the foundation of induction therapy for primary CNS lymphoma (PCNSL), a gold-standard regimen has yet to be established. A 10-case-based survey, to assess the practice patterns at key decision-points in adult PCNSL management outside of clinical trials, was distributed through IPCG, HOVON, and AAN Neuro-Oncology Section. Eighty-five responses were collected from North American (N=42), European (N=33), Asian (N=7), and other countries (N=3) from neurologist neurooncologists (N=35), hem-onc neurooncologists (N=24), hematologist-oncologists (N=18), neurosurgeons (N=5), radiation-oncologist (N=2), and hematopathologist (N=1). The most common first-line induction regimen was R-MP+/-V: rituximab, HD-MTX, procarbazine, +/-vincristine (N=28) followed by MATRix: HD-MTX, cytarabine, thiotepa, rituximab (N=23), then R-MT: rituximab, HD-MTX, temozolomide (N=19). For elderly patients, R-MP+/-V remained most common (N=32). The majority preferred to omit intra-CSF chemotherapy (N=50). The most preferred consolidation after complete response was high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT, N=57), or high-dose cytarabine (N=17) in elderly patients. In cases of partial response, the most common approach was still HDC-ASCT (N=24). For stable disease, participants would move to various salvage chemotherapy (N=33), continue additional induction (N=39), or to move to radiotherapy (N=10). If early progression was noted, the most preferred approach was non-methotrexate chemotherapy (N=31). For recurrences after previous complete response and HDC-ASCT consolidation, the majority preferred to try chemotherapy before moving to radiotherapy in scenarios < 1 year (N=64) or > 1 year from consolidation (N=68), and even if the performance status was poor (N=57). Close to half (N=34) participants felt there is a role for stereotactic radiosurgery in various clinical settings. This survey noted clear consensus to use multi-drug MD-MTX based chemotherapy, and common induction regimens, however, highlighted a great variety of treatment preferences after first-line therapy even amongst disease experts through clinical consortiums, suggesting likely wider range of treatments and disease response in larger community settings.

BIOM-08. LEVERAGING CSF PROTEOMICS TO OPTIMIZE CNS LYMPHOMA MANAGEMENT

Abstract INTRODUCTION Despite exquisite responses to initial therapy for CNS lymphoma (CNSL), relapse is common and overall responses are disappointing compared to other non-CNS diffuse large B-cell lymphomas. Incorporation of multi-agent intraventricular chemotherapy (MAIVC) alongside systemic therapy is novel. Identification of minimally-invasive biomarkers of response to MAIVC are necessary but lacking. The objectives of this study were to 1) identify baseline cerebrospinal fluid (CSF)-based proteomic predictive biomarkers of MAIVC treatment response and 2) identify tumor burden markers for longitudinal monitoring of MAIVC treatment response in CNSL. METHODS A cohort of patients with primary or secondary CNSL that were treated with MAIVC at Penn State Health (2015-2021) was included. Each MAIVC cycle was administered via Ommaya reservoir and included a 2-drug combination comprised of methotrexate, rituximab, cytarabine, etoposide, topotecan, gemcitabine, or thiotepa. Patient-matched CSF was sampled at pre- and post-therapeutic endpoints and profiled using shotgun proteomics. Patients were grouped by treatment response status. Early responders were defined as patients that achieved malignant cell-free CSF within 6 MAIVC cycles, whereas never responders were those patients that i) did not achieve malignant cell-free CSF by endpoint or ii) required salvage surgery or radiation during MAIVC. RESULTS 59 patients were included (21 primary; 38 secondary CNSL) with a median age of 66 years (range 25-90) and median number of MAIVC cycles of 8 (range 2-23). A proteomic-based classifier, comprised of SGCE, LCP1 and AGRN, discriminated between early and never responders with an AUROC of 0.95. Comparison of CSF at baseline (<3 cycles MAIVC) vs. post-treatment (>12 cycles MAIVC) identified H3F3A, YWHAE, LCP1, CA1 and GAPDH as tumor burden biomarkers. CONCLUSION Here we developed a proteomic signature capable of predicting CNSL patient response to MAIVC, with potential to improve clinical decision making. Furthermore, the biomarkers associated with tumor burden represent important indicators of treatment response. Ongoing efforts are underway to evaluate these candidates as actionable therapeutic targets.

INNV-30. TOXICITIES AND OUTCOME AFTER CD19-DIRECTED CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY FOR NEUROLYMPHOMATOSIS

Abstract BACKGROUND Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis. METHODS Neurolymphomatosis treated with CD19-CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification. Management, and response rates were recorded. RESULTS Eleven neurolymphomatosis cases, who had received a median 2 prior PNS-directed treatments (range: 1-3) before CD19-CAR T-cell exposure, were identified. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome was detected in 8/11 (73%; grade 1: N = 7; grade 2: N =1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions were achieved in three cases (27%), of which two are still sustained now 9 and 46 months after CD19-CAR T-cell infusion. All radiographic responses were associated with remission of neurological symptoms. CONCLUSIONS CD19-CAR T-cell treatment was well tolerated and yielded promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier, and toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.

RADT-39. CENTRAL NERVOUS SYSTEM BRIDGING RADIOTHERAPY (CNS-BRT) ACHIEVES RAPID CYTOREDUCTION PRIOR TO CAR T-CELL THERAPY FOR AGGRESSIVE B-CELL LYMPHOMAS

Abstract BACKGROUND CAR T-cell therapy (CART) for central nervous system lymphoma (CNSL) is a promising strategy, yet responses are frequently not durable. Bridging radiotherapy (BRT) is used for extra-cranial lymphoma to improve CART outcomes through cytoreduction of high-risk lesions. We hypothesized that CNS-BRT would achieve similar, significant cytoreduction prior to CART for CNSL. METHODS We analyzed CNSL patients with non-Hodgkin B-cell lymphomas who received CNS-BRT prior to commercial CART. Best CNS response post-CART was evaluated using the International Primary CNS Lymphoma Collaborative Group (IPCG) or RANO for parenchymal or leptomeningeal lesions, respectively. Cytoreduction from CNS-BRT was calculated as change in lesion size prior to CART. RESULTS Twelve patients received CNS-BRT, with median follow up of 11.8m (IQR: 8.5–21.9). Ten had CNSL (9 secondary, 1 primary) and 2 patients had epidural disease (evaluable for toxicity). All ten CNSL patients had progressive disease at the time of CNS-BRT. RT targets included whole brain (n=3), involved site (partial) brain (n=4), involved site spine (n=4), and orbits (n=1) with median dose 24Gy (range: 15-33). 1/12 patients experienced grade ≥3 cytokine release syndrome (CRS), and 3/12 patients experienced grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS). CNS-BRT achieved a 74.0% (95%CI: 62.0–86.0) mean reduction in lesion size from baseline (p=0.014) at a median of only 12d from BRT completion and pre-CART infusion. Best CNS response included 8 complete responses (CR), 1 partial response (PR), and 1 progressive disease (PD). Three patients experienced CNS relapse outside the BRT field for a 12-month estimated risk of CNS progression post-CART of 20.0% (95%CI: 3–49). CONCLUSIONS Early data suggest CNS-BRT achieves rapid cytoreduction and favorable CNS response. The rates of severe CRS/ICANS were similar to comparison series of CNSL patients treated with CART without BRT suggesting an acceptable safety profile. Our data support further study of BRT as a bridging strategy for CNSL-directed CART.

Application of CAR-T cell therapy in B-cell lymphoma: a meta-analysis of randomized controlled trials.

This study aims to compare the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) immunotherapy with standard treatment for B-cell lymphoma, providing evidence-based support for the more efficient use of CAR-T cell immunotherapy. We conducted a comprehensive literature search of high-quality randomized controlled trials (RCTs) on CAR-T therapy for B-cell lymphoma in the following databases: Wanfang, Web of Science, CNKI, VIP database, and PubMed, up to February 2024. The outcome measures included objective remission rate (ORR), complete remission rate (CRR), and incidence of adverse reactions. Subgroup analysis was performed based on the differences in co-stimulatory domains. Meta-analysis was conducted using Review Manager 5.4 and Stata software. A total of five RCTs involving 1670 patients were included in this meta-analysis. The results showed that the CAR-T treatment group had significantly higher ORR (RR: 1.47, 95% CI 1.23-1.76, I2 = 80%, p < 0.0001), CRR (RR: 2.19, 95% CI 2.16-3.79, I2 = 93%, p = 0.005), cytokine release syndrome (CRS) incidence (RR: 34.51, 95% CI 2.27-523.78, I2 = 98%, p = 0.01), neurotoxicity (NT) incidence (RR: 6.00, 95% CI 1.82-19.75, I2 = 80%, p = 0.003), neutropenia incidence (RR: 1.39, 95% CI 1.02-1.88, I2 = 93%, p = 0.03), leukopenia incidence (RR: 1.39, 95% CI 1.04-1.87, I2 = 61%, p = 0.03), and headache incidence (RR: 1.56, 95% CI 1.25-1.95, I2 = 34%, p < 0.0001) compared to the standard treatment group. Subgroup analysis based on co-stimulatory domains revealed that the 4-1BB subgroup had higher incidences of CRR, CRS, NT and leukopenia than the CD28 subgroup; however, the CD28 subgroup exhibited higher ORR and neutropenia than the 4-1BB subgroup. CAR-T cell immunotherapy demonstrates superior efficacy compared to standard therapy in treating B-cell lymphoma. However, CAR-T treatment can lead to adverse reactions such as CRS and NT. Infusion of an appropriate dose of CAR-T cells (e.g., 100 × 106) may be a strategy to mitigate the risk of CRS and NT.

Assessment of fitness for bleomycin use and management of bleomycin pulmonary toxicity in patients with classical Hodgkin lymphoma: A British Society for Haematology Good Practice Paper.

This good practice paper (GPP) is intended to support clinicians in assessing patient fitness for bleomycin and in management of bleomycin pulmonary toxicity (BPT) where it occurs. Bleomycin, originally developed as an antibiotic in the 1960s, has been a cornerstone of therapy for classical Hodgkin lymphoma (CHL) since results of its use in combination with doxorubicin, vincristine and dacarbazine (ABVD) were first published by Bonadonna etal in 1975 1. The same author recognised high rates of respiratory morbidity in these patients 2, and bleomycin-;related pulmonary toxicity (BPT) is now a well-;recognised and feared complication with its use. ABVD and BEACOPP/ BEACOPDac (bleomycin, cyclophosphamide, etoposide, doxorubicin, vincristine and prednisolone, with procarbazine or dacarbazine) are standard first-;line treatments in CHL patients, but considerable variation remains in assessing patient fitness for bleomycin both clinically and with respiratory investigations. A recent survey of British haematologists regularly using bleomycin revealed that 87.5% have no local protocols for assessing patients in an evidence-;based fashion, with wide variations in practice captured in the same survey (personal data). A working group was established and a literature review undertaken with the goal of presenting practical recommendations for clinicians regarding bleomycin use based on available evidence and expert opinion.

Cancer cachexia and weight loss before CAR T-cell therapy for lymphoma are independently associated with poor outcomes

AbstractChimeric antigen receptor (CAR) T-cell therapy has transformed the care of lymphoma, yet many patients relapse. Several prognostic markers have been associated with CAR T-cell outcomes, such as tumor burden, response to bridging chemotherapy, and laboratory parameters at the time of lymphodepletion or infusion. The effect of cancer cachexia and weight loss before CAR T cells on toxicity and outcomes is not well understood. Here, we present a retrospective single-institution cohort study of 259 patients with lymphoma treated with CAR T cells between 2017 and 2023. We observed that patients with >5% decrease in their body mass index in the 3 months preceding CAR T-cell treatment (weight loss group; all meeting one of the commonly accepted definitions of cancer cachexia) had higher disease burden and inflammatory parameters (C-reactive protein, ferritin, interleukin-6, and tumor necrosis factor α) at the time of lymphodepletion and CAR T-cell infusion. Patients with weight loss experienced higher rates of grade 3+ neurotoxicity and early hematotoxicity, but those effects were not seen upon multivariable adjustment. However, in both univariate and multivariable analysis, patients with weight loss had worse response rates, overall survival, and event-free survival, indicating that weight loss is an independent poor prognostic factor. Our data suggest that weight loss in the 3 months preceding CAR T-cell therapy represents a worrisome “alarm signal” and a potentially modifiable factor, alongside tumor burden and inflammation, and warrants further investigation in patients treated with CAR T-cell therapy.

Alternative therapy for lymphoma with febrile neutropenia using traditional Chinese medicine: A case report

IntroductionFebrile neutropenia is a common complication in patients undergoing chemotherapy for hematologic malignancies and is associated with significant morbidity and mortality. Primary granulocyte colony-stimulating factor (G-CSF) prophylaxis is consistently associated with a notable reduction in the risk of febrile neutropenia. However, the use of G-CSF in patients who are already neutropenic from chemotherapy remains controversial. Studies have shown that 12.9% of cancer patients incorporate traditional Chinese medicine (TCM) to alleviate chemotherapy side effects in Taiwan; thereby providing an alternative management strategy for neutropenic fever in cancer patients. Case presentationThis is an 18-year-old female with newly diagnosed precursor T-lymphoblastic lymphoma. After chemotherapy, the patient developed febrile neutropenia. Despite the use of antibiotics and G-CSF, the febrile neutropenia persisted for two months. Approximately ten days after the initiation of traditional Chinese medicine decoction with the strategy of tonifying the spleen and stomach, clearing yin fire, and uplifting yang, her absolute neutrophil count (ANC) had gradually increased. Additionally, after two weeks of treatment, her fever subsided. The patient continued with chemotherapy and was discharged in stable condition. DiscussionAntibiotic use aligns with the TCM perspective of an “attack” approach. Conversely, our TCM decoction was designed to raise the ANC by tonifying the spleen and stomach, clearing Yin Fire, and uplifting Yang. Li Dongyuan, one of the four great masters of the Jin Yuan Dynasty, created the formula: Bupiwei Shengyang Sanhuo Decoction that is notable in this regard. The herbs in our decoction have shown hematopoietic and myelosuppression-alleviating effect. For many patients who do not respond adequately to G-CSF alone, integrative treatments involving both TCM and Western medicine can offer additional therapeutic benefits by increasing blood cell counts.

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.

Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma.

The treatment landscape for relapsed/refractory follicular lymphoma (RR-FL) is marked by a pivotal debate between chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs). While both CAR-T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons. Key trials, such as the ZUMA-5 study, underscore axicabtagene ciloleucel (axi-cel)'s efficacy in treating RR-FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso-cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR-FL patients. Thus, CAR-T therapy offers potential curative benefits with a single infusion. However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles. When considering cost-effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost-effectiveness considerations are essential; while CAR-T therapies incur higher initial costs, their potential for long-term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR-FL management strategies.

Risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma.

BACKGROUND: Osteoporosis is characterized by a discharge of bone mass, which contributes to the development of pathological fractures. Hodgkin's lymphoma can cause a violation of bone microarchitectonics. The development of Hodgkin's lymphoma is characteristic of young people, on average from 16 to 35 years old. Early diagnosis of osteoporosis in young patients with Hodgkin's lymphoma is an urgent issue due to a prolonged asymptomatic decrease in bone mineral density, with the development of pathological fractures. AIMS: to study the risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma who received pathogenetic therapy. MATERIALS AND METHODS: the study included 63 patients with Hodgkin's lymphoma and 30 volunteers from the control group. All patients answered the questionnaire questions in order to identify risk factors for osteoporosis. Common risk factors included: gender, age, body mass index; fractures in the history of the patient and his immediate family; taking hormone replacement therapy, proton pump inhibitors, glucocorticosteroids; the presence of concomitant diseases; the presence of amenorrhea in women; physical activity level and calcium intake. Specific factors include the use of chemotherapy drugs for the treatment of Hodgkin's lymphoma. The data obtained were subjected to statistical analysis in order to identify the most significant risk factors. RESULTS: osteopenia and osteoporosis are a serious complication of antitumor therapy of Hodgkin's lymphoma in young people. Unfortunately, today a small number of researchers are engaged in the problem of identifying predictors of osteoporosis in young patients with Hodgkin's lymphoma. Because of this study, the most significant risk factors for the development of osteoporosis were identified, namely low physical activity, taking proton pump inhibitors and glucocorticosteroids, as well as the development of secondary postcytostatic amenorrhea in women. CONCLUSIONS: timely diagnosis and prevention of osteoporosis in young patients will prevent a decrease in bone mineral density and reduce the risks of early disability in this category of patients.

Antibody-Based Therapies for Peripheral T-Cell Lymphoma.

While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the emergence of new therapies provide hope for the future. In this review, we explore four areas of current and evolving antibody-based strategies for the treatment of peripheral T-cell lymphoma (PTCL): monoclonal antibodies (mAbs), bispecific antibodies (BsAs), chimeric antigen receptor T-cell therapy (CAR-T), and antibody-drug conjugates (ADCs). As part of this discussion, we will also include limitations, lessons learned, and potential future directions.

Biological Findings and Clinical Outcomes in Patients Treated With R-CHOP Plus High-Dose Methotrexate as First-Line Therapy in Large B-Cell Lymphoma With Testis Involvement.

Primary testicular lymphoma (PTL) is a rare occurrence of diffuse large B-cell lymphoma (DLBCL) that accounts for 1%-2% of all cases. Nodal DLBCL with testis involvement (DLBCL-T) and PTL are associated with poor prognosis, with high incidence of central nervous system relapse. Fifteen patients (median age 60 years) with PTL (n = 5) or DLBCL-T (n = 10) received high-dose methotrexate + R-CHOP. Overall, complete response (CR) rate was 73% and overall response rate 86%. With a 3.9-year median follow-up, 100% of patients with PTL had CR and none relapsed. On the contrary, 55% of DLBCL-T patients achieved CR among which only one was still in remission at the end of follow-up. Molecular parallels between PTL and Primary CNS Lymphoma (PCNSL) suggest shared origins, urging further research for tailored treatments and enhanced understanding of these lymphomas' biology.

A small molecule BCL6 inhibitor effectively suppresses diffuse large B cell lymphoma cells growth.

The B-cell lymphoma 6 (BCL6) transcription factor plays a key role in establishment of germinal center (GC) formation. Diffuse large B cell lymphoma (DLBCL) originates from the GC reaction due to dysregulation of BCL6. Disrupting BCL6 and its corepressors interaction has become the foundation for rationally designing lymphoma therapies. However, BCL6 inhibitors with good activities in vitro and in vivo are rare and there are no clinically approved BCL6 inhibitors. Here, we discovered and developed a novel range of [1,2,4] triazolo[1,5-a] pyrimidine derivatives targeting BCL6/SMRT interaction. The analogue WK692 directly bound BCL6BTB, disrupted BCL6BTB/SMRT interaction and activated the expression of BCL6 downstream genes inside cells, inhibited DLBCL growth and induced apoptosis in vitro, inhibited GC formation, decreased proportion of follicular helper T (Tfh) cells and impaired immunoglobulin affinity maturation. Further studies showed that WK692 inhibited the DLBCL growth without toxic effects in vivo and synergizes with the EZH2 and PRMT5 inhibitors. Our results demonstrated that WK692 as a BCL6 inhibitor may be developed as a novel potential anticancer agent against DLBCL.

Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study.

The optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group, 89.2% of CT-group and 78.8% of no-bridge-group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT-group, 28.2% in the CT-group, and 47.6% in the no-bridge-group (p = 0.044, CT-bridging vs RT-bridging); 1-year OS was 86.7% in the RT-group, 52.7% in the CT-group and 69% in the no-bridge-group (p = 0.025, CT-bridging vs RT-bridging). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT-group, 3.3% RT-group, 7.7% no-bridge group; p = 0.05). In conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site.

New and emerging therapies in cutaneous T-cell lymphoma

Mycosis Fungoides (MF) is the most common cutaneous T-cell lymphoma that typically presents in the early phase as inflammatory erythematous patches or plaques, with epidermotropism as the histopathological hallmark of the disease. Traditionally, in the early stages, non-aggressive options represent the first-line strategy: topical corticosteroids, phototherapy, radiotherapy and occasionally adopting a 'wait-and-see' approach for minimally symptomatic patients. In patients with advanced or recurrence disease, good results can be achieved with immune modifiers, chemotherapeutic agents, total skin irradiation or extracorporeal photochemotherapy and maintenance therapy is often required. The past decade has seen an expansion of therapies that can be used in this setting by increasing new therapeutic strategies. Herein are resumed the key advancements coming from recently published trials.

Efficacy of thiotepa-conditioned autologous stem-cell transplantation as consolidation therapy for primary leptomeningeal malignant lymphoma: a case report and review of literature.

Primary leptomeningeal malignant lymphoma (PLML) is a rare subtype of primary central nervous system lymphoma (PCNSL). Treatment is often based on PCNSL, but currently there is no established treatment strategy due to its rarity. We report a case of a 46-year-old male diagnosed with PLML through cerebrospinal fluid cytology and flow cytometry, presenting with multiple cranial nerve palsies and L5 radiculopathy. The patient achieved complete remission (CR) with R-MPV (rituximab, methotrexate, procarbazine, and vincristine) combined with intrathecal chemotherapy (methotrexate, cytarabine, and prednisolone). This was followed by autologous stem-cell transplantation (ASCT) using a thiotepa-based conditioning regimen, resulting in sustained CR. A literature review on the use of ASCT for PLML revealed three reported cases, including ours, all achieving CR with ASCT and minimal adverse events. These findings suggest that ASCT can be a promising consolidation therapy for PLML. Further studies are needed to establish standardized treatment protocols for this rare condition.

Prognostic significance of fludeoxyglucose positron emission tomography delta radiomics following bridging therapy in patients with large B-cell lymphoma undergoing CAR T-cell therapy.

Bridging radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of cytoreduction during bRT impacts outcomes. We retrospectively reviewed patients with LBCL treated with bRT followed by CAR T-cell therapy. Metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), SUVmean, and total lesion glycolysis (TLG) were extracted from F18-fluorodeoxyglucose positron emission tomography (PET) scans acquired prior to bRT and between completion of bRT and CAR T-cell infusion. Delta radiomics based on changes of these values were then calculated. The association between delta radiomics and oncologic outcomes [progression-free survival (PFS), freedom from distant progression (FFDP), and local control (LC)] were then examined. Thirty-three sites across 23 patients with LBCL were irradiated. All metabolically active disease was treated in 10 patients. Following bRT, median overall decreases (including unirradiated sites) in MTV, SUVmax, SUVmean, and TLG were 22.2 cc (63.1%), 8.9 (36.8%), 3.4 (31.1%), and 297.9 cc (75.8%), respectively. Median decreases in MTV, SUVmax, SUVmean, and TLG in irradiated sites were 15.6 cc (91.1%), 17.0 (74.6%), 6.8 (55.3%), and 157.0 cc (94.6%), respectively. Median follow-up was 15.2 months. A decrease in SUVmax of at least 54% was associated with improved PFS (24-month PFS: 83.3% vs. 28.1%; p = 0.037) and FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). A decrease in MTV of at least 90% was associated with improved FFDP (24-month FFDP: 100% vs. 62.4%; p < 0.001). LC was improved in sites with decreases in SUVmax of at least 71% (24-month LC: 100% vs. 72.7%; p < 0.001). Decreases of MTV by at least 90% (100% vs. 53.3%; p = 0.038) and TLG by at least 95% (100% vs. 56.3%; p = 0.067) were associated with an improved complete response rate. bRT led to substantial reductions in MTV, SUVmax, SUVmean, and TLG. The relative extent of these decreases correlated with improved outcomes after CAR T-cell infusion. Prospective cohorts should validate the value of interim PET following bRT for quantifying changes in disease burden and associated prognosis.

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.