Siobhan Glavey

The chorioallantoic membrane (CAM) is a well-vascularised extra-embryonic membrane that supports avian embryonic development and can be used as an implantation site for xenograft models of various cancers. CAM tumour research models are powerful and versatile, offering a rapid, cost-effective and ethical complement to mouse xenograft studies. Their capacity for real-time observation of tumour growth, angiogenesis and metastasis within an immunocompetent living organism is particularly compelling. While CAM models have been extensively utilised for investigating solid cancers, such as breast, lung and pancreatic, their potential for haematological malignancy research remains comparatively underexplored. This review examines the relevance, advantages and translational potential of avian CAM models in studying blood cancers. Their applications across three primary categories are discussed—leukaemias, lymphomas and myelomas—highlighting experimental approaches that replicate aspects of human disease progression and therapeutic responsiveness. Moreover, the review evaluates species-specific considerations relevant to model fidelity, including evolutionary distance and functional parallels between avian and human haematopoiesis. These comparisons underscore both the opportunities and limitations for utilising CAM models in haematologic malignancy research. For their potential to investigate mechanisms of cancer development and treatment in simple but immunocompetent in vivo settings, we propose that CAM tumour models offer high value as a bridge between in vitro and mammalian in vivo studies for haematology translational research.

The chorioallantoic membrane (CAM) is a well-vascularised extra-embryonic mem-brane that supports avian embryonic development, and can be used as an implantation site for xenograft models of various cancers. CAM tumour research models are powerful and versatile, offering a rapid, cost-effective and ethical complement to mouse xenograft studies. Their capacity for real-time observation of tumour growth, angiogenesis and metastasis within an immunocompetent living organism are particularly compelling. While CAM models have been extensively utilised for investigating solid cancers such as breast, lung and pancreatic, their potential for haematological malignancy research remains comparatively underexplored. This review examines the relevance, advantages and translational potential of avian CAM models in studying blood cancers. Their ap-plications across three primary categories are discussed – leukaemias, lymphomas and myelomas – highlighting experimental approaches that replicate aspects of human disease progression and therapeutic responsiveness. Moreover, the review evaluates species-specific considerations relevant to model fidelity, including evolutionary dis-tance and functional parallels between avian and human haematopoiesis. These com-parisons underscore both the opportunities and limitations for utilising CAM models in haematologic malignancy research. For their potential to investigate mechanisms of cancer development and treatment in simple but immunocompetent in vivo settings, we propose that CAM tumour models offer high value as a bridge between in vitro and mammalian in vivo studies for haematology translational research.

Multiple myeloma (MM) is an incurable blood malignancy characterized by the clonal expansion of plasma cells and the secretion of monoclonal immunoglobulins. High‐risk MM, defined by specific cytogenetic abnormalities, poses significant therapeutic challenges and is associated with inferior survival outcomes compared to standard‐risk disease. Although molecularly targeted therapies have shown efficacy in other hematologic malignancies, currently venetoclax is the only targeted therapy approved for MM (t(11;14)). However, chromosome 1q gains, amplifications, and 1p deletions are frequently observed in MM, and have been linked to drug resistance and poor patient prognosis. Accordingly, this review focuses on emerging MM precision therapies capable of targeting dysregulated genes within these regions. It addresses gene therapies, small molecule inhibitors and monoclonal antibodies currently under investigation to antagonize oncogenic drivers including MCL‐1, BCL9, F11R, and CKS1B, all of which are implicated in cell survival, proliferation or drug resistance. In conclusion, the link between chromosome 1 abnormalities and high‐risk disease in MM patients offers a compelling rationale to identify and explore therapeutic targeting of chromosome 1 gene products as a novel precision medicine approach for a poorly served patient population.

Despite significant improvements in the treatment of multiple myeloma (MM), it remains mostly incurable, highlighting a need for new therapeutic approaches. Patients with high-risk disease characteristics have a particularly poor prognosis and limited response to current frontline therapies. The recent development of immunotherapeutic strategies, particularly T cell-based agents have changed the treatment landscape for patients with relapsed and refractory disease. Adoptive cellular therapies include chimeric antigen receptor (CAR) T cells, which have emerged as a highly promising therapy, particularly for patients with refractory disease. Other adoptive cellular approaches currently in trials include T cell receptor-based therapy (TCR), and the expansion of CAR technology to natural killer (NK) cells. In this review we explore the emerging therapeutic field of adoptive cellular therapy for MM, with a particular focus on the clinical impact of these therapies for patients with high-risk myeloma.

Multiple myeloma (MM) is the second most common haematological neoplasm of adults in the Western world. Overall survival has doubled since the advent of proteosome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. However, patients with adverse cytogenetics or high-risk disease as determined by the Revised International Staging System (R-ISS) continue to have poorer outcomes, and triple-refractory patients have a median survival of less than 1 year. Bispecific antibodies (BsAbs) commonly bind to a tumour epitope along with CD3 on T-cells, leading to T-cell activation and tumour cell killing. These treatments show great promise in MM patients, with the first agent, teclistamab, receiving regulatory approval in 2022. Their potential utility is hampered by the immunosuppressive tumour microenvironment (TME), a hallmark of MM, which may limit efficacy, and by undesirable adverse events, including cytokine release syndrome (CRS) and infections, some of which may be fatal. In this review, we first consider the means of enhancing the efficacy of BsAbs in MM. These include combining BsAbs with other drugs that ameliorate the effect of the immunosuppressive TME, improving target availability, the use of BsAbs directed against multiple target antigens, and the optimal time in the treatment pathway to employ BsAbs. We then discuss methods to improve safety, focusing on reducing infection rates associated with treatment-induced hypogammaglobulinaemia, and decreasing the frequency and severity of CRS. BsAbs offer a highly-active therapeutic option in MM. Improving the efficacy and safety profiles of these agents may enable more patients to benefit from these novel therapies and improve outcomes for patients with high-risk disease.

Multiple myeloma (MM) is an aggressive plasma cell malignancy with high degrees of variability in outcome, some patients experience long remissions, whilst others survive less than two years from diagnosis. Therapy refractoriness and relapse remain challenges in MM management, and there is a need for improved prognostication and targeted therapies to improve overall survival (OS). The past decade has seen a surge in gene expression profiling (GEP) studies which have elucidated the molecular landscape of MM and led to the identification of novel gene signatures that predict OS and outperform current clinical predictors. In this review, we discuss the limitations of current prognostic tools and the emerging role of GEP in diagnostics and in the development of personalised medicine approaches to combat drug resistance.

The development of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is well recognised in multiple myeloma (MM). SIADH, due to either MM or Bortezomib can be hazardous as severe hyponatremia may develop if large volumes of hypotonic intravenous fluid are used as an adjunct to chemotherapy. We report a case of Bortezomib-induced SIADH, in whom the use of tolvaptan, a vasopressin receptor-2 antagonist, permitted the continuation of triple combination anti-MM therapy with lenalidomide, Bortezomib and dexamethasone (RVD) in a female with aggressive disease, without the development of hyponatremia. Our patient had a rapid relapse, in which the use of Bortezomib as part of an RVD regimen was life-saving. The use of tolvaptan allowed continuation of therapy that is usually halted in other similarly reported cases. This case highlights the possible use of vaptans, which allows an aquaresis to occur by blocking the antidiuretic effects of vasopressin, as a treatment for Bortezomib-induced hyponatremia.