CNS Lymphoma: Clinical Pearls and Management Considerations

Michel, Michelot; Lucke-Wold, Noelle; Hosseini, M. Reza; Panther, Eric; Reddy, Ramya; Lucke‐Wold, Brandon

doi:10.31579/2692-9406/121

Cited by 3 publications

(1 citation statement)

References 105 publications

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“…The prognosis of relapsed/refractory (R/R) central nervous system lymphoma (CNSL) has been extremely poor, with a median overall survival (OS) of only 4 months. 1 2 Over the past decades, despite improvement of clinical outcomes for R/R CNSL patients by high-dose methotrexate (HD-MTX)-based chemotherapy, small-molecule inhibitors, radiation therapy, and salvage high-dose chemotherapy with autologous stem cell transplantation (ASCT), 3 poor prognosis of patients at high-risk remained to be challenging, 4 5 highlighting the need for new therapeutic strategies and agents. Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of R/R large B-cell lymphoma (R/R LBCL).…”

Section: Introductionmentioning

confidence: 99%

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Yu,

Huang,

Mei

et al. 2024

J Immunother Cancer

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BackgroundRelapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the “real-world” use of relma-cel, especially for patients with CNS involvement.Patients and methodsRetrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events.ResultsAmong the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55–618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12–32 days).ConclusionsThis study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.

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Section: Introductionmentioning

confidence: 99%

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Yu,

Huang,

Mei

et al. 2024

J Immunother Cancer

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The effects of thymoquinone and cytozine arabinoside on apoptosis and cell proliferation in acute myeloide leukemia

Aslı¹,

Kara²,

Tural³

et al. 2022

Glob J Cancer Ther

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Purpose: The aim of this study was to investigate the effects of a chemotherapeutic agent Cytosine Arabinoside (Ara-C) and a natural anticancer agent of Thymoquinone (TQ) on apoptosis and cell proliferation of AML cell lines (Kasumi-6) both alone and in combined form. Material and method: Kasumi-6 AML cells were treated with three different doses of Ara-C (0.1, 0.5 and 1 µmol) and TQ (25, 50 and 100 µM) for 48 and 72 hours incubations. After Annexin V and Propidium Iodide (PI) staining, apoptosis, viability, and cell proliferation were evaluated for each group in flow cytometry. Results: As a result, AML cell lines showed a statistically significant difference in a single treatment of the active substances. Their combined treatment showed an increase in apoptosis and a decrease in viability in both groups at 48 and 72 hours incubation times (p < 0.001). In each group, it was observed that apoptosis was increased and viability was decreased and consequently cell proliferation was suppressed. Conclusion: Ara-C was used for the first time in this study with TQ in AML. It was determined that the combined use of TQ and Ara-C did not have a synergistic effect on apoptosis.

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Optimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting

Krishnamurthy,

Oh,

Gautham

et al. 2024

Cureus

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Introduction: Brain metastases are difficult to treat due to the blood-brain barrier limiting the delivery of therapeutic agents to the brain effectively. Intraventricular drug delivery has not been well studied for intraaxial pathologies. However, our prior work demonstrated that intraventricular drug delivery in a hyperosmolar vehicle showed preferential accumulation of drug within breast cancer tissue compared to surrounding brain parenchyma. The focus of this study was to explore the molecular parameters of intraventricular drug administration that may optimize drug delivery to intra-axial brain metastases. Our hypothesis was that a low molecular weight drug with a high osmolarity solution would increase drug delivery to tumor tissue.Methods: We used an intracerebral breast cancer tumor model in adult female nude rats divided into six experimental groups. We examined three iron-labeled dextran molecules (3 kD, 5 kD, and 10 kD) in 337 mOsm/L solution and three different osmolarities of delivery solution (307, 353, and 368 mOsm/L) with 10 kD dextran. 7T magnetic resonance imaging (MRI) was used to analyze dextran distribution at different time points. All animals were sacrificed after two hours, and the quantity of dextran particles was determined by histopathology.Results: Breast cancer tumor cells were successfully implanted in all rats. The MRI quantification of dextran concentration was well corroborated by histopathology. Varying the molecular size of dextran resulted in the smallest molecule reaching peak levels in tumor tissue earlier than the larger molecules, but the larger molecules remained concentrated in tumor tissue for a longer time. Varying the osmolarity of the delivery solution resulted in the preferential accumulation of 10 kD dextran in tumor tissue except for when dextran was delivered in 368 mOsm/L solution where no preferential distribution was seen.Conclusion: Hyperosmolar intraventricular delivery of chemotherapeutic drugs could be effective in preferentially delivering drugs to abnormal tumor tissues.

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CNS Lymphoma: Clinical Pearls and Management Considerations

Cited by 3 publications

References 105 publications

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China

The effects of thymoquinone and cytozine arabinoside on apoptosis and cell proliferation in acute myeloide leukemia

Optimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting

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