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Chimeric antigen receptor (CAR) T‐cell therapy has become a commercially available treatment option for relapsed or refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) with two or more lines of prior therapies, and recently for high‐risk r/r DLBCL with one prior line of therapy. The successful development of CAR T‐cell therapy for multiple relapsed DLBCL has led to a boom in subsequent trials that investigated its utility in patients with other r/r B‐cell lymphoma subtypes. However, CAR T‐cell therapy is a multistep process that includes leukapheresis and manipulation which take several weeks. Therefore, patients with rapidly progressing or bulky disease may not be able to complete the therapeutic regimen involving CAR T‐cell products. This raises the question of the generalizability of the results of pivotal studies to the entire population. In this review, we summarize the development of CAR‐T cell therapy for B‐cell lymphoma and discuss strategies to further improve the clinical outcomes of this treatment. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) as first‐line treatment, we performed this post‐hoc analysis of patients with advanced indolent B‐cell lymphoma in a randomized clinical trial wherein six cycles of R‐CHOP were administered every 2–3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676–9.466) and high‐ (OR 2.236, 95% CI 0.160–31.226) risks, B symptoms (OR 2.091, 95% CI 0.747–5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634–5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow‐up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806–8.575) and high‐risk FLIPI (OR 4.401, 95% CI 0.186–104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer‐term analysis had a greater impact on HT. G3A and high‐risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced‐stage FL in future trials, particularly to address the unmet needs of patients with POD24. [ABSTRACT FROM AUTHOR]

Summary: Anti‐CD20 antibody in combination with chemotherapy extends overall survival (OS) in untreated advanced‐stage follicular lymphoma (FL), yet the optimal associated therapy is unclear. Data on the cumulative incidence of secondary malignancies postrelapse after conventional immunochemotherapy are scarce. A long‐term analysis of rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) as first‐line treatment was conducted in a randomised clinical trial. A six‐cycle R‐CHOP regimen was administered every 2 or 3 weeks without rituximab maintenance. A prespecified evaluation was conducted 15 years after the completion of enrolment, following initial analysis results that showed no significant differences in outcomes at the 3‐year mark. In‐depth analyses were performed on the cohort of 248 patients with FL who were allocated to the two treatment arms. With a median follow‐up period of 15.9 years, the 15‐year OS was 76.2%. There were no protocol treatment‐related deaths, nor were there any fatal infections attributable to subsequent lymphoma treatment. At 15 years, the cumulative incidence of non‐haematological and haematological malignancies was 12.8% and 3.7% respectively. Histological transformation appeared after a median of 8 years. R‐CHOP maintains safety and efficacy in patients with advanced FL over extended follow‐up, making it a viable first‐line option for patients with advanced‐stage FL. [ABSTRACT FROM AUTHOR]

Abstract: Patients with relapsed or refractory (R/R) mature natural killer cell and T-cell lymphoma have limited treatment options. To evaluate pralatrexate's performance and factors influencing its safety and efficacy in R/R peripheral T-cell lymphoma (PTCL), we performed a pooled analysis of data from 4 similarly designed, regulatory-mandated prospective clinical trials. Of 221 patients (median age, 59 years; 67.0% male) in the study population, 48.9% had PTCL not otherwise specified (PTCL-NOS), 21.3% angioimmunoblastic T-cell lymphoma, and 11.8% ALK-negative anaplastic large cell lymphoma (ALCL). Patients received pralatrexate for a median of 2.56 months (range, 0.03-24.18) and had a 40.7% objective response rate with a median duration of response of 9.1 months, progression-free survival 4.6 months, and overall survival 16.3 months. The most common treatment-related all-grade adverse events were stomatitis, thrombocytopenia, white blood cell count decrease, pyrexia, and vomiting. Subgroup exploratory analyses suggest improved efficacy with 1 prior line of chemotherapy vs 2 or ≥4 prior lines; PTCL-NOS or ALCL vs transformed mycosis fungoides; chemotherapy and transplant before pralatrexate vs chemotherapy alone or chemotherapy with other nontransplant treatments. In conclusion, these pooled analysis results further support using pralatrexate in patients with R/R PTCL. Prospective studies are needed to confirm the findings of subgroups analyses., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

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The leaves of Odontonema strictum, a tropical plant used for its antihypertensive properties, are rich in nutrients and biologically active phytochemicals, such as β-sitosterol, stigmasterol, umuravumbolide, deacetylumuravumbolide, dideacetylboronolide, deacetylboronolide, verbascoside, and isoverbascoside. In addition, its roots are rich in β-sitosterol, stigmasterol, and the iridoid glycoside β-O-methyl-unedoside. Ingestion of the roots was reported to have a sedative effect in a dog was previously reported on a dog eating the roots of this plant. In the present study, we report for the first time the cell proliferation- and neurite outgrowth-promoting effects in PC12 neuronal cells of the isolated organic compounds and crude extracts from O. strictum. Pituitary adenylate cyclase-activating peptide (PACAP) and quercetin were used as positive controls. At the concentration of 0.2 μg/mL, β-sitosterol was more potent than quercetin and displayed the same activity (>45 μm/cell) as PACAP (100 nM). At a low concentration (0.04 μg/mL), verbascoside and isoverbascoside showed the strongest neurite outgrowth-promoting effect (neurite length of 30 to 35 μm/cell). Our results indicate that phytomedicines made from O. strictum may be useful in preventing neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There are two main types of clinical trials: industry-sponsored trials and investigator-initiated trials. Both of these, like the two sets of wheels on a car, are essential to development of treatments. Numerous clinical trials have been conducted in multiple myeloma, contributing to the development of new drugs and the current treatment landscape. Highly effective novel immunotherapies, such as bispecific antibodies and chimeric antigen receptor T-cell therapy, have emerged, and could be incorporated into the treatment landscape in the near future. However, given the improved performance of current standard therapies, the drawbacks (e.g., toxicity) of immunotherapy can be expected to outweigh the benefits (efficacy) in some patients. Therefore, clinical trials are designed to evaluate treatments stratified based on factors such as post-treatment efficacy and disease risk, and stratified treatment approaches are increasingly being considered as well as one-size-fits-all approaches to treatment development. In addition, the use of real-world data is being explored to make clinical trials more efficient. These approaches are expected to further improve the individualization and efficiency of multiple myeloma treatment.

High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.