Expert Opinion on Biological Therapy最新文献

Introduction: Small-cell lung cancer (SCLC) is a rapidly progressive form of cancer often expressing DLL3. Tarlatamab is a bispecific antibody which blocks DLL3-related downstream pathways and activates antitumor host immunity. It is currently authorized in the U.S.A. for the treatment of extensive SCLC.

Areas covered: This is a review evaluating the basic pharmacology and clinical data regarding tarlatamab. Most data come from SCLC; in the other two diseases, tarlatamab is in early clinical development.

Expert opinion: Tarlatamab is an effective therapy mainly in relapsed/progressed SCLC, and its assessment in limited SCLC alone or combined with other therapies is supported by the existing data.

Introduction: Talquetamab is a GPRC5DxCD3 T-cell-engaging bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma. GPRC5D represents a novel and emerging target in antimyeloma therapy, and there is substantial drug development for new therapies targeting this antigen.

Areas covered: Herein, we review the efficacy, safety, and future development directions of talquetamab, including emerging talquetamab-based combination regimens and ongoing clinical trials. We will also review the growing landscape of GPRC5D-targeting immunotherapies in development for multiple myeloma, including CAR-T and trispecific antibodies.

Expert opinion: Talquetamab, a GPRC5D-targeting bispecific antibody, was FDA-approved in 2023 for relapsed/refractory multiple myeloma after 4 or more prior lines of therapy. In contrast to the historic overall response rate (ORR) of 29.5%, talquetamab monotherapy achieved a promising ORR of ~70% in a triple-class-exposed population. Real-world evidence supports talquetamab as a bridging therapy to CAR-T. Notable adverse drug reactions include CRS, dysgeusia, nail/skin toxicities, and infections, which are often manageable but can be persistent. Sequencing studies suggest talquetamab retains efficacy before or after BCMA-directed therapies without diminishing effectiveness. Potential future directions for talquetamab include combination regimens with other antimyeloma therapies. Additional GPRC5D-directed therapies are also under development, including trispecific antibodies and CAR-T.

Introduction: Bispecific antibodies (BsAbs) are a novel class of immunotherapy agents that engage endogenous T cells to target and eradicate malignant B cells by simultaneously binding CD3 and CD20. BsAbs such as epcoritamab, glofitamab, and mosunetuzumab have demonstrated substantial efficacy across both aggressive and indolent B-cell non-Hodgkin lymphomas (B-NHL), with largely manageable safety profiles. Their off-the-shelf administration offers a practical alternative to CAR T-cell therapy, particularly for patients who are transplant-ineligible or lack access to cellular approaches.

Areas covered: This review provides a comprehensive overview of BsAbs in B-NHL. We detail pivotal studies in relapsed/refractory (R/R) DLBCL, FL, and MCL, highlighting single-agent outcomes and emerging combination strategies. Approaches incorporating BsAbs into cytotoxic backbones and antibody-drug conjugates, as well as chemotherapy-free regimens such as BsAbs combined with lenalidomide, are discussed. We also examine their potential to address poor-risk disease features and historically refractory subsets.

Expert opinion: BsAbs represent a major advance in B-NHL, offering high rates of deep remission with predictable safety and outpatient feasibility. As trial data continues to mature, BsAb-based regimens are poised to become foundational across multiple lines of therapy, reshaping expectations for patients with both aggressive and indolent lymphomas.

Objectives: To assess the use of rituximab in non-Hodgkin lymphoma (nHL) and chronic lymphocytic leukemia (CLL) in light of the evolving regulatory landscape, including the introduction of subcutaneous and biosimilar formulations in the past decade.

Methods: A retrospective cohort study was conducted using the VALORE distributed database network covering nine Italian regions (2012-2022). Patients with at least one rituximab dispensing and a previous nHL or CLL diagnosis were included. Annual prevalence rates (per 10,000 inhabitants) were estimated for intravenous originator, biosimilar, and subcutaneous formulations. Switch rates between originator and biosimilar were assessed by index year at 1 year of follow-up.

Results: We selected 73,870 prevalent rituximab users. Prevalence peaked in 2019 (4.6/10,000) and declined in 2022 (3.4/10,000), with originator use dropping from 4.2 to 0.2/10,000. Among 24,258 incident users (nHL: 21,001; CLL: 3,257), originator-to-biosimilar switch rates rose from 12.5% (2017) to 33.3% (2022) in nHL (p < 0.05) and from 10.3% (2017) to 78.3% (2020) in CLL (p < 0.05). Biosimilar-to-originator switches were rare in CLL (3.8%) but more frequent in nHL (15.3%), due to subcutaneous switch.

Conclusions: These findings show a shift from originator to biosimilar rituximab in Italy, alongside a recent decline in its use, likely driven by COVID-19 pandemic and new treatment strategies.