Safety and Efficacy of Teclistamab in Patients With Relapsed or Refractory AL Amyloidosis.

Introduction: Teclistamab has demonstrated deep responses in patients with multiple myeloma in the MajesTEC-1 study. However, the safety and efficacy of teclistamab in patients with AL amyloidosis are unknown.

Methods: We retrospectively analyzed patients with biopsy-proven relapsed/refractory AL amyloidosis who were treated with teclistamab from December 2022 to February 2024 at the University of Pennsylvania.

Human IL-6 fosters long-term engraftment of patient-derived disease-driving myeloma cells in immunodeficient mice.

Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned human IL-6-transgenic (hIL-6-transgenic) NSG (NSG+hIL6) mice reliably support the engraftment of malignant and premalignant human plasma cells, including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and postrelapse myeloma, plasma cell leukemia, and amyloid light chain amyloidosis.

Human IL-6 fosters long-term engraftment of patient derived disease-driving myeloma cells in immunodeficient mice.

Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with monoclonal gammopathy of undetermined significance, pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis.

Progressive multifocal leukoencephalopathy in multiple myeloma.

Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal demyelinating disease of the central nervous system caused by reactivation of the JC virus in the context of immune suppression such as HIV, malignancy, and certain immunomodulatory medications. PML has been reported only rarely in multiple myeloma patients, and its presenting features and natural history in this population are not well known. We describe six cases of PML among multiple myeloma patients treated at our institution between 2013 and 2022, including two that developed on or shortly after treatment with recently developed BCMA-directed immunotherapies.

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

Unlabelled: We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)-negative complete response/stringent complete response.

Radiation Therapy for Plasma Cell Disease of the Brain and Skull: Poor Palliation and Survival After Treatment for Central Nervous System Involvement.

Purpose: Myeloma lesions of the head can present with central nervous system (CNS) involvement (leptomeningeal disease or brain metastasis), cranial neuropathy (CN), or impending neurologic involvement (INI). We analyzed response and survival after palliative radiation therapy (RT) to the brain and/or skull for myeloma lesions to determine whether CNS involvement fared worse than other RT indications.

Methods And Materials: We retrospectively analyzed 54 palliative RT courses administered at our institution from 2008 to 2019.

Detailed phenotyping reveals distinct trajectories of cardiovascular function and symptoms with exposure to modern breast cancer therapy.

Background: Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership.

Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysis.

Importance: Cardiovascular adverse events (CVAE) with carfilzomib in patients with multiple myeloma can be potentially life-threatening and remain incompletely characterized. We performed the first systematic review and meta-analysis of carfilzomib-associated CVAE.

Objective: To determine the incidence of carfilzomib-associated CVAE and to compare the rates of carfilzomib CVAE among different doses and companion therapies.

Proteasome inhibitor associated thrombotic microangiopathy.

A variety of medications have been implicated in the causation of thrombotic microangiopathy (TMA). Recently, a few case reports have emerged of TMA attributed to the proteasome inhibitors (PI) bortezomib and carfilzomib in patients with multiple myeloma. The aim of this case series was to better characterize the role of PI in the etiology of drug-induced TMA.

Multiple myeloma precursor disease.

Recent data indicate that multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. Currently, multiple myeloma is a clinical diagnosis based on manifestations including hypercalcemia, renal failure, anemia, and bone lesions, whereas MGUS and smoldering myeloma are diagnosed based on laboratory abnormalities. Current clinical markers allow for more individualized risk stratification and counseling of these patients.

Racial disparities in incidence and outcome in multiple myeloma: a population-based study.

Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some prior studies suggest inferior survival in blacks; others suggest similar survival. Using the original 9 Surveillance, Epidemiology, and End Results registries, we conducted a large-scale population-based study including 5798 black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006.

Smoldering (asymptomatic) multiple myeloma: revisiting the clinical dilemma and looking into the future.

Recent studies show that multiple myeloma (MM) is consistently preceded by an asymptomatic precursor state. Smoldering MM (SMM) is a MM precursor defined by an M-protein concentration >or= 3 g/dL and/or >or= 10% bone marrow plasma cells, in the absence of end-organ damage. Compared with individuals diagnosed with monoclonal gammopathy of undetermined significance (MGUS), patients with SMM have a much higher annual risk of developing MM.

A case study progression to multiple myeloma.

Multiple myeloma consistently is preceded by precursor states, which often are diagnosed incidentally in the laboratory. This case report illustrates the clinical dilemma of progression from precursor to full malignancy. The article also discusses future directions in management and research focusing on myelomagenesis.