Concurrent TTR and AL Amyloidosis: Diagnostic Challenges and Clinical Implications.

Background: Amyloidosis is a disorder characterized by misfolded protein deposits in organs, often manifesting as cardiac disease.

Case Summary: A 60-year-old male with a history of isolated proteinuria and recent fat biopsy-proven transthyretin (TTR) amyloidosis was referred to us for evaluation of cardiac involvement with amyloidosis. He underwent a technetium pyrophosphate scan which showed Perugini grade 3 uptake concerning for cardiac involvement.

GCK inhibition enhances iberdomide antimyeloma effects by promoting IKZF1 degradation via a CRBN-independent mechanism.

Our recent study identifies germinal center kinase (GCK) as a novel therapeutic target in RAS-mutated multiple myeloma (MM). Inhibiting GCK downregulates critical transcriptional factors, notably IKZF1/3, BCL-6, and c-MYC proteins, leading to MM cell growth inhibition and cell death. Distinct from immunomodulatory drug (IMiD)-induced IKZF1/3 degradation, GCK inhibition triggers IKZF1/3 proteolysis through a cereblon (CRBN) E3 ligase-independent mechanism.

Therapeutic anti-cancer vaccines: a systematic review of prospective intervention trials for common hematological malignancies.

Background: This review comprehensively assesses all prospective trials on anti-cancer vaccines for common hematological malignancies by analyzing trial designs, endpoints, and whether these endpoints are met across these trials.

Methods: We included onco prospective clinical trials involving therapeutic anti-cancer vaccines for hematological malignancies published up to May 2025. We excluded retrospective cohort studies, case reports, non-research opinion publications, and studies not related to hematological malignancies.

Quality of Patient-Reported Outcomes in Multiple Myeloma Randomized Controlled Trial Protocols and Publications According to the SPIRIT-PRO and CONSORT-PRO guidelines: A Systematic Review.

Background: Patient-reported outcomes (PROs) are now frequently incorporated into multiple myeloma (MM) randomized controlled trials (RCTs) to help inform clinical decision making. Although the quality of PRO components in cancer RCT protocols is generally recognized as suboptimal, there are limited data on adherence to international quality standards in MM RCT protocols.

Methods: We performed a systematic review to identify MM RCTs published between January 2014 and June 2023 that utilized the EORTC QLQ-C30 questionnaire.

Safety and Efficacy of Elranatamab in Patients with Relapsed and/or Refractory immunoglobulin Light-Chain Amyloidosis.

Immunoglobulin light chain (AL) amyloidosis is a plasma cell disorder characterized by progressive organ dysfunction secondary to deposition of organized immunoglobulin light chain aggregates. Achievement of rapid and deep normalization of involved immunoglobulin free light chains is necessary to maximize chances of reversibility of organ dysfunction, which in turn results in improved quality and length of life. There are no FDA-approved therapies for patients with relapsed and/or refractory immunoglobulin light chain (AL) amyloidosis.

Patient Preferences on Clinical Decision Making in Multiple Myeloma.

Purpose: To better understand the priorities that guide patients with multiple myeloma, we surveyed patients on four different treatment scenarios, each of treatment strategies shown to improve progression-free survival (PFS) but offering similar overall survival (OS) outcomes.

Methods: We conducted a survey using the HealthTree Cure Hub by the HealthTree Foundation, the largest online portal for people with plasma cell dyscrasias.

Results: The primary analysis cohort included 466 participants with myeloma, while an additional 297 responses from patients with smoldering myeloma or monoclonal gammopathy of uncertain significance were analyzed separately.

Effect of Intravenous Immunoglobulin (IVIG) Supplementation on infection-free survival in recipients of BCMA-directed bispecific antibody therapy for multiple myeloma.

The main objective of this multi-institutional study is to understand the effect of primary intravenous immunoglobulin (IVIG) replacement on clinical outcomes in recipients of BCMA-directed bispecific antibody (bsAb), where infection remains an important cause of morbidity and mortality. This is a retrospective study of patients treated with either standard of care teclistamab or BCMA-directed investigational bsAb between Nov 2017 and Dec 2023. Primary IVIG prophylaxis was defined as starting IVIG prior to first documented infection.

The Impact of Melphalan Conditioning and CD34 Cell Dose and Schedule on Post-Transplant Outcomes in AL Amyloidosis.

The optimal conditioning schedule and CD34+ cell dose for autologous stem cell transplantation (ASCT) for AL amyloidosis is unknown. Patients (n = 1704) who underwent ASCT for AL amyloidosis between 2003 and 2020 in 9 centers were included. Data on melphalan conditioning dose, number of conditioning days, whether a rest day between conditioning and stem cell infusion was given or not, and infused CD34 cell dose were collected.

A model for predicting day-100 stem cell transplant-related mortality in AL amyloidosis.

Autologous stem cell Transplant (ASCT)-related mortality (TRM) in AL amyloidosis remains elevated. AL amyloidosis patients (n = 1718) from 9 centers, transplanted 2003-2020 were included. Pre-ASCT variables of interest were assessed for association with day-100 all-cause mortality.

Improved Outcomes of Myeloma Cast Nephropathy in Newly Diagnosed Multiple Myeloma With Modern Anti-Myeloma Therapies.

Myeloma cast nephropathy (MCN) is a driver of renal failure in newly diagnosed multiple myeloma (NDMM) and has been historically associated with increased early mortality. Since patients with moderate to severe renal insufficiency are typically excluded from trials, we performed a retrospective study to characterize modern-era outcomes in MCN. We reviewed 274 consecutive NDMM patients from 2017 to 2023 at an academic center and identified 46 patients (16.

Treatment of Refractory Monoclonal Immunoglobulin Deposition Disease With BCMA Bispecific Antibody.

Monoclonal immunoglobulin deposition disease (MIDD) is characterized by deposits of intact monoclonal immunoglobulin protein, most commonly in the kidney, but other organs such as the heart can be involved. Patients are treated with plasma cell-directed therapies. Here we describe the first reported case of a patient with refractory MIDD with renal and cardiac involvement who was successfully treated with a BCMA-drected therapy.

Patient-reported outcome domains in multiple myeloma randomized controlled trials and association with survival outcomes.

Patient-reported outcomes (PROs) are crucial endpoints in multiple myeloma (MM) randomized controlled trials (RCTs), yet there is significant variability in their methodology and reporting. Our study aimed to (a) identify the most commonly pre-specified PRO domains in MM RCTs and those most responsive to modern therapies, and (b) examine the association between PROs and progression-free survival (PFS)/overall survival (OS). We performed a systematic review of MM RCTs that used EORTC QLQ-C30 and published between 01/2014-06/2023.

Evaluating early intervention in smoldering myeloma clinical trials: a systematic review.

Background: Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM.