Clinical and Pathological Characteristics of Non-AL Amyloidosis MGRS: A Single-Center Experience Over 10 Years.

Objective: Monoclonal gammopathy of renal significance (MGRS) is a heterogeneous and relatively recently defined disorder that encompasses many kidney and hematologic pathologies. MGRS remains a rare disease and there is a need for more literature regarding its treatment and outcomes. In this study, we share our center's experience with MGRS including incidence of different kidney pathologies, clone type, kidney and hematologic response, and progression-free survival.

Prevalence and Significance of Incidental PET/CT Findings of Cancer Detected in Patients Evaluated for Their Primary Hematologic Malignancy: A Systematic Review.

In the evaluation of a patient's primary hematologic malignancy, positron emission tomography/computed tomography (PET/CT) imaging may incidentally detect a concerning abnormality suggestive of a second concurrent cancer. Despite accounting for nearly 10% of all cancers diagnosed in Canada, there has yet to be a systematic review focused on the prevalence and significance of these incidental PET/CT findings in the context of primary hematologic malignancies. As such, a systematic search strategy was employed on MEDLINE and Embase to document the prevalence and clinical significance of incidental PET/CT findings suggestive of a second concurrent cancer detected in patients evaluated for their primary hematologic malignancy.

Impact of soluble BCMA and non-T-cell factors on refractoriness to BCMA-targeting T-cell engagers in multiple myeloma.

Adoptive T-cell therapy is a promising therapy for multiple myeloma (MM), but its efficacy hinges on understanding the relevant biologic and predictive markers of response. B-cell maturation antigen (BCMA) is a key target antigen in MM with active development of multiple anti-BCMA T-cell engagers (TCEs) and chimeric antigen receptor T-cell therapies. The regulation of surface BCMA expression by MM cells, which leads to shedding of soluble BCMA (sBCMA), has triggered debate about the significance of sBCMA as a predictive marker and its potential impact on treatment outcomes.

Timing antigenic escape in multiple myeloma treated with T-cell redirecting immunotherapies.

Recent data highlight genomic events driving antigen escape as a recurring cause of chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (TCE) resistance in multiple myeloma (MM). Yet, it remains unclear if these events, leading to clonal dominance at progression, result from acquisition under treatment selection or selection of pre-existing undetectable clones. This differentiation gains importance as these immunotherapies progress to earlier lines of treatment, prompting the need for innovative diagnostic testing to detect these events early on.

Cereblon-Targeting Ligase Degraders in Myeloma: Mechanisms of Action and Resistance.

Cereblon-targeting degraders, including immunomodulatory imide drugs lenalidomide and pomalidomide alongside cereblon E3 ligase modulators like iberdomide and mezigdomide, have demonstrated significant anti-myeloma effects. These drugs play a crucial role in diverse therapeutic approaches for multiple myeloma (MM), emphasizing their therapeutic importance across various disease stages. Despite their evident efficacy, approximately 5% to 10% of MM patients exhibit primary resistance to lenalidomide, and resistance commonly develops over time.

Current use of bispecific antibodies to treat multiple myeloma.

Targeted immunotherapy has significantly improved the outcome of patients with hematological malignancies by leveraging the power of the immune system to eliminate tumor cells. In multiple myeloma (MM), bispecific T-cell engagers (BsAb) targeting B-cell maturation antigen (BCMA), G protein-coupled receptor, class C, group 5, member D (GPRC5D), and Fc receptor-like 5 (FcRL5) have already demonstrated remarkable clinical activity in triple-class refractory patients. However, responses to BsAb are not universal, and resistance often emerges while on therapy.

ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma.

Unlabelled: Immunomodulatory drugs (IMiD) are a backbone therapy for multiple myeloma (MM). Despite their efficacy, most patients develop resistance, and the mechanisms are not fully defined. Here, we show that IMiD responses are directed by IMiD-dependent degradation of IKZF1 and IKZF3 that bind to enhancers necessary to sustain the expression of MYC and other myeloma oncogenes.

Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma.

B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy.

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response.

Monoclonal Gammopathy of Undetermined Significance in Patients With Transthyretin Amyloidosis (ATTR): Analysis Using the iStopMM Criteria.

Introduction: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin amyloid (ATTR). We used the iStopMM study revised reference ranges for serum free light-chain (sFLC) corrected for eGFR to identify ATTR patients with light-chain MGUS (LC-MGUS). Characteristics and frequencies of the ATTR cohort with underlying MGUS was compared to a cohort of MGUS patients without ATTR.

Real-world Outcomes With Cumulative Bortezomib Dose and Efficacy in the Treatment of Transplant-ineligible Multiple Myeloma With Cyclophosphamide, Bortezomib, and Dexamethasone.

Background: Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients.

Patients And Methods: Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate.

Cyclophosphamide, Bortezomib and Methylprednisolone (CyBorMe) for the Treatment of AL Amyloidosis: Initial Experience From a Single Center.

The use of cyclophosphamide, bortezomib and dexamethasone (CyBorD) is widely accepted in the treatment of AL amyloidosis (AL). Recently, the substitution of dexamethasone by methylprednisolone (CyBorMe) appeared to improve response rates and survival outcomes. All consecutive newly diagnosed AL amyloidosis treated with CyBorMe from 01/19 to 08/20 were evaluated.

Impact of COVID-19 on the Diagnosis and Management of Multiple Myeloma: Experience from a Canadian Center.

Background: The impact of coronavirus disease-19 on the management of multiple myeloma (MM) has been recognized. However, the real effect on clinical outcomes remains poorly understood.

Objective: We describe a local experience of the management of MM patients and report their outcomes during the current pandemic.

N-Terminal pro-brain natriuretic peptide (NTproBNP) in patients with symptomatic multiple myeloma: report from a single institution.

Elevated levels of serum cardiovascular markers including natriuretic peptides (NPs) such as amino terminal pro-brain natriuretic peptide (NTproBNP) have been associated with disease severity and survival in cancer patients and more recently in multiple myeloma (MM). In the present study, we retrospectively reviewed 87 consecutive symptomatic TEMM (transplant-eligible) and 126 TIMM (transplant-ineligible) patients treated at our institution that did undergo NTproBNP testing from 2017 to 2020. Median age at diagnosis was 59.

Treatment response measurements and survival outcomes in a cohort of newly diagnosed AL amyloidosis.

Introduction: The assessment of AL amyloidosis response is based on serum free light chains (sFLC) levels, and serum and urine monoclonal protein investigations. Recently, difference between involved and uninvolved free light chains (dFLC), involved free light chain (iFLC) and complete response (CR) has been reported as independent predictor of survival and a refinement of the hematological response criteria has been proposed by several groups.

Methods: In the current study, all consecutive newly diagnosed symptomatic AL amyloidosis patients were evaluated.

Monoclonal Gammopathy of Undetermined Significance Clinic during the Coronavirus Disease-19 Pandemic: Caring for the Vulnerable in an Academic Medical Center.

Background: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic.

Objective: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes.

Methods: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020).