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Summary: The growing use of frontline lenalidomide treatment in multiple myeloma (MM) is increasing the proportion of lenalidomide‐refractory patients, which may limit the efficacy of subsequent lines of treatment (LOT). This systematic literature review (January 2008–October 2023) of clinical trials (CT) and real‐world studies (RW) assessed treatment outcomes in adults with relapsed/refractory MM (RRMM) who were previously treated with ≥1 LOT, progressed and were lenalidomide‐refractory. Medline, EMBASE and additional electronic databases were searched for articles published in English. Primary outcomes included progression‐free survival (PFS), overall survival (OS) and overall/objective response rate (ORR); 24 CT and 19 RW were included. For CT, the population‐weighted mean of median PFS (CT = 14) and OS (CT = 6) were shorter in the lenalidomide‐refractory cohort (months: 8.8 [n = 2699] and 21.7 [n = 1066], respectively) than the intent‐to‐treat population (months: 13.8 [n = 5380] and 35.9 [n = 2264], respectively); the population‐weighted (N = 2142) mean ORR for lenalidomide‐refractory patients (CT = 18) was 56.0%. RW reported considerable variation in PFS (RW = 7), OS (RW = 8) and ORR (RW = 8); and median PFS (RW = 2; months) was lower in lenalidomide/bortezomib‐refractory (5.5/5.5; n = 81/n = 25) versus lenalidomide‐refractory (7.3/8.0; n = 81/n = 61) patients. These data provide evidence that clinical trials and real‐world outcomes are suboptimal in lenalidomide‐refractory patients with RRMM, highlighting the need to improve treatment options for this population. [ABSTRACT FROM AUTHOR]

There have been significant advances in the treatment of multiple myeloma in the last two decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, ∼10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival (OS). In the setting of prolonged long-term OS due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation (KTx). Unfortunately, most data regarding outcomes of KTx in patients with myeloma come from single-center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and KTx outcomes in this complex population. We further discuss the future of KTx in patients with paraproteinemia. [ABSTRACT FROM AUTHOR]

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the US. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White patients at diagnosis (median 68 vs. 71 years) and more likely to be female (53.4% vs. 43.5%). Rates of high-risk cytogenetics and 1q21+ were similar between races/ethnicities. The most common primary regimen used was lenalidomide-bortezomib-dexamethasone (50.1% of NH Black/AA and 48.1% of NH White patients). Receipt of stem cell transplantation during first LOT was less common among NH Black/AA (16.5%) than NH White (21.9%) patients. Unadjusted RW progression-free survival (rwPFS) and overall survival (rwOS) were similar between races/ethnicities. After multivariable adjustment, NH Black/AA race/ethnicity was associated with slightly inferior rwPFS (hazard ratio [HR]=1.13; 95% confidence interval [CI]: 1.01-1.27). The difference in rwOS (HR=1.12; 95% CI: 0.98-1.28) was not statistically significant. In general, associations between risk factors for rwPFS and rwOS were consistent between races/ethnicities. Findings from this analysis help to inform clinicians about the impact of race/ethnicity on MM treatment paradigms and outcomes in the US.

Purpose: Quantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM)., Experimental Design: Using LC-MS/MS data, Ig constant region peptides, and transitions were selected for LC-MRM MS. Quantitative assays were used to assess Igs in serum from 83 patients. RNA sequencing and peptide-based LC-MRM are used to define peptides for quantification of the disease-specific Ig., Results: LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1-4, IgA1-2, IgM, IgD, and IgE, as well as kappa (κ) and lambda (λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 MM cell line and two MM patients., Conclusions and Clinical Relevance: LC-MRM assays targeting constant region peptides determine the type and isoform of the involved Ig and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher inter-assay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)