Leukemia & Lymphoma最新文献

The cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations. This study introduces gneSeqCOO, an algorithm using bulk RNA Sequencing (RNASeq) profiles of individual tumor biopsies for COO classification based on a fixed reference. This method produced consistent per-sample results and was robust to variation in RNA quality and sequencing bias. Validation in >1000 DLBCL samples showed high concordance with the NanoString LST assay, even in cohorts containing only one COO subtype. gneSeqCOO presents a robust and versatile alternative to existing assays, potentially reducing the need for additional samples where RNASeq was already generated. The package is available at https://github.com/Genentech/gneSeqCOO.

Using immunotherapeutic agents like inotuzumab ozogamicin (InO), blinatumomab, or chimeric antigen receptor T (CAR T)-cell therapy in frontline adult B-cell acute lymphoblastic leukemia (B-ALL) therapy is promising. These agents are mostly well tolerated and have different toxicity profiles than conventional chemotherapy, enabling their combination with chemotherapy. Additionally, they have often been shown to overcome the traditional adverse ALL risk features. Recently blinatumomab was approved as part of consolidation therapy in MRD negative B-ALL; however, a significant proportion of patients had progressed or relapsed before reaching the timepoint of blinatumomab administration. Including InO/blinatumomab from induction onwards could induce earlier and deeper remissions. Modifications of dosing and administration schedules, as with the fractionated InO schedule with low-intensity chemotherapy, and subcutaneous blinatumomab, appear to reduce the toxicity and improve the anti-ALL efficacy. CAR T-cell therapies like brexucabtagene autoleucel as a consolidation approach have shown positive outcomes. The feasibility of using CAR T-cells to reduce the need for long-drawn maintenance and the need for allogeneic hematopoietic stem cell transplantation (HSCT) are questions of ongoing clinical trials. Newer generation CAR T-cell products like obecabtagene autoleucel appear as effective and safer. Better disease monitoring through next generation sequencing based measurable residual disease analysis could identify patients where treatment intensification including HSCT, or deintensification, is suitable.

Prognostic assessment in chronic lymphocytic leukemia (CLL) is essential for delivery of timely, personalized therapy. TP53 status, karyotype, IGHV mutational status, minimal residual disease (MRD), gene mutations and markers of cell proliferation were important prognostic tools in the era of chemo-immunotherapy (CIT). With BCL2 inhibitors (BCL2i), outcome is still impacted by IGHV status, TP53 status, complex karyotype, and achievement of undetectable MRD. On the other hand, BTK inhibitors (BTKi) are agnostic to IGHV status, rarely cause MRD negative remissions and are less clearly impacted by TP53 status. Although based on less mature data, outcomes with BCL2i/BTKi combinations are likely influenced by TP53 and IGHV status. Responses to non-covalent BTKI (ncBTKI) are impacted by the mechanism of resistance to previous covalent BTKi. Finally, responses to chimeric antigen receptor T cell therapy (CAR-T) appear independent of TP53 status, but dependent on overall T- cell fitness.

Cardiovascular adverse events (CVAEs) are recognized complications of chimeric antigen receptor (CAR) T-cell therapies. However, data are lacking regarding subtypes of adverse events that develop in patients with different malignancies, and little is known about the timeframe in which different cardiotoxicities are most likely to occur post-CAR T-cell therapies. In this study, 211 patients, including 138 lymphoma patients and 66 myeloma patients who received CAR T-cell therapies were retrospectively identified. Of these, 42 patients (19.9%) developed CVAEs post-treatment. Myeloma patients predominantly experienced heart failure while lymphoma patients predominantly experienced arrhythmia. Severe CVAEs were observed even at >12 months post-treatment. Lower baseline global longitudinal strain was significantly associated with development of post-CAR T-cell therapy CVAEs in both lymphoma and myeloma patients. These findings highlight the spectra of post-CAR T-cell cardiotoxicities in lymphoma and myeloma patients and the importance of echocardiography for pretreatment risk stratification and long-term surveillance.

Subcutaneous (SC) rituximab has demonstrated advantages over intravenous (IV) administration; however, insufficient data exist on its use with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Chinese patients with diffuse large B-cell lymphoma (DLBCL). This multicenter, phase II, randomized, controlled study was conducted across China between February 2021 and October 2022. Fifty adult patients with previously untreated CD20-positive DLBCL were randomized to receive one cycle of IV rituximab and seven cycles of SC rituximab (R^SC-CHOP; n = 26), or eight cycles of IV rituximab (R^IV-CHOP; n = 24), combined with six or eight cycles of CHOP. Geometric mean ratio of trough rituximab serum concentration of SC to that of IV rituximab (C_trough,SC/C_trough,IV) at cycle 7 was 1.52 (90% CI: 1.28-1.79), demonstrating non-inferiority of C_trough,SC. The complete response rate was similar in both treatment arms. SC rituximab is a viable option in Chinese patients with untreated CD20-positive DLBCL, potentially reducing administration burden (ClinicalTrials.gov identifier: NCT04660799).

Patients participating in clinical trials are highly selected and may not represent the general population. The pivotal study of teclistamab (MajesTEC-1), a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, demonstrated impressive response rates and progression free survival in relapsed/refractory multiple myeloma (RRMM) with acceptable toxicity. We performed a retrospective study of 58 patients treated as standard of care at four US academic centers to determine how these results translated to the real-world. Most patients (87.9%) would not have been eligible for the MajesTEC-1 study due to either disease related factors, patient related comorbidities or socio-economic/geographical factors. Despite these 'less-favorable' characteristics we observed similar efficacy and toxicity to MajesTEC-1. A meta-analysis with six other published real-world series (n = 546) confirmed these results. These data support the significant clinical activity of teclistamab in RRMM and highlights the importance of real-world data to accompany the pivotal trial data to further inform daily clinical practice.

Follicular lymphoma (FL) represents the second most frequent type of non-Hodgkin lymphoma and the most common indolent histology. The disease course of FL is heterogeneous, likely resulting from diverse molecular and immunological features that drive a broad spectrum of clinical presentations. While some patients with low-volume and asymptomatic disease are suitable for observation, patients with high tumor burden, advanced-stage, or symptomatic disease more often necessitate treatment initiation. The decision to begin therapy is personalized and typically initiated when GELF criteria are met. The introduction of novel agents has modified the treatment landscape for FL, allowing for more personalized strategies based on the specific characteristics of patients and diseases. In this review, we discuss the indications for treatment initiation and optimization, focusing on long-term follow-up of pivotal studies and emerging non-chemotherapy regimens. We further consider effective novel combination regimens and future directions for the evolution of frontline immunotherapy for the treatment of patients with FL.

This retrospective study aimed to evaluate the efficacy and safety of PBVD (pegylated liposomal doxorubicin [PLD], bleomycin, vinblastine, and dacarbazine) in the first-line treatment of classical Hodgkin lymphoma (cHL) patients with cardiovascular risk factors. Overall, 84 patients (53 had stage I-II and 31 had stage III-IV disease) received PBVD. The median PLD treatment duration was 16 weeks (interquartile range [IQR]: 8-24) for stage I-II and 24 weeks (IQR: 12-24) for stage III-IV. Among them, 56 (66.7%) received radiotherapy (45 with stage I-II and 11 with stage III-IV disease). Seventy-four (88.1%) patients achieved complete response. At a median follow-up of 49.7 months, 2- and 5-year progression-free survival were both 83.2%, and overall survival was 98.7% and 94.9%. Adverse events occurred in 73.8% of patients, including 7.1% cardiac events. No treatment-related deaths were observed. This approach showed a favorable benefit-to-risk profile in this population.