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Abstract: Optimal therapy for the growing number of patients with lenalidomide (LEN)-refractory multiple myeloma in their first relapse remains poorly defined. We therefore undertook a randomized phase 2 study to evaluate the efficacy and safety of combining the oral proteasome inhibitor ixazomib (IXA) with pomalidomide (POM) and dexamethasone (DEX) in this patient population. The overall response rate (ORR) for POM-DEX was 43.6%, and for IXA-POM-DEX, it was 63.2%. The depth of response, measured by the attainment of at least a very good partial response, favored triplet therapy over doublet therapy (28.9% vs 5.1%; P = .0063). A preplanned interim analysis after 75% of the progression events had occurred demonstrated an improvement in progression-free survival (PFS) that favored IXA-POM-DEX and that crossed the predefined boundary of superiority, leading to release of the study results. With additional follow-up, the median PFS for POM-DEX was 7.5 months (95% confidence interval [CI], 4.8-13.6 months) vs 20.3 months for IXA-POM-DEX (95% CI, 7.7-26.0 months; hazard ratio, 0.437; upper 90% bound = 0.657). The ORR and median PFS for 26 of 30 eligible patients who crossed over from the doublet to the triplet therapy at disease progression was 23.1% and 5.6 months, respectively. Overall survival was similar between the 2 groups. More hematologic toxicities were seen with the triplet therapy, but nonhematologic adverse events were similar between the 2 arms. Our data support further testing of this all-oral triplet therapy in comparison with current standard triplet therapy in the context of phase 3 studies for patients with LEN-refractory disease at first relapse. This trial was registered at www.clinicaltrials.gov as #NCT02004275., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: The therapeutic landscape in relapsed/refractory multiple myeloma (RRMM) has changed rapidly, with twenty-two drug approvals since 2012. We characterized population-level trends in RRMM therapy selection, survival and cost outcomes associated with RRMM treatment over time., Materials and Methods: Our cohort included adults diagnosed with multiple myeloma (MM) in the SEER-Medicare database from 2007-2017 who received at least one antimyeloma agent. MM-directed therapies and lines of therapy were identified. Changes in 2LT regimens over time were described. Trends in overall survival from 2LT initiation over time were analyzed using a Cox proportional hazards model adjusting for factors associated with survival in MM. Trends in mean inflation-adjusted cost per 12 months of 2LT were analyzed using JoinPoint analysis., Results: A total of 9,822 patients met eligibility criteria, of whom 5,866 (59.7%) received 2LT. By 2018, 46% of 2LT regimens contained at least one agent approved in 2012 or later. Year of 2LT initiation was associated with improved overall survival (HR 0.78 per 5 years, 95% CI 0.74-0.84) after adjustment. Costs associated with 2LT increased over the study period, and the rate of cost increase increased significantly after 2012 (0.89%/year vs. 9.9%/year, P < .001), with higher total costs for regimens containing newer novel agents (mean $224,193 vs. $189,381, P < .001) CONCLUSION: Overall survival after initiation of 2LT has improved, however this has been accompanied by significant increases in costs of RRMM treatment, particularly for patients receiving newer novel agents. These findings provide useful context for existing and future drug approvals in RRMM., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Geriatric assessment (GA)-guided supportive care programs have been successful in improving treatment outcomes for older adults with solid-organ cancers. This study aimed to evaluate the feasibility of a GA-guided supportive care program among older adults treated for multiple myeloma (MM)., Materials and Methods: The study utilized an existing registry of adults with plasma cell disorders at the University of North Carolina. Patients with MM, aged 60 or older, and having a GA-identified deficit in one or more problem area were offered referrals to supportive care resources during routine visits. Problem areas included physical function deficits, polypharmacy, and anxiety or depression. Patients with physical function deficits were offered referral to physical therapy (PT), those with polypharmacy to an Oncology Clinical Pharmacist Practitioner (CPP), and those with mental health symptoms to the Comprehensive Cancer Support Program (CCSP)., Results: Of the 58 individuals identified as having at least one deficit on the GA, PT was the most commonly identified relevant resource (79%), followed by CPP visits (57%). Among individuals that were offered referral(s) to at least one new supportive care resource, the acceptance rate was 50%. Referral acceptance rates were highest among those recommended for a CPP visit (55% of those approached) and lowest for CCSP (0%)., Discussion: The study examined the feasibility and acceptability of a referral program for supportive care resources among older adults with MM who have deficits on GA. The most commonly identified deficit was physical functioning, followed by polypharmacy and mental health. The study found that physical interventions and referrals to CPPs were the most accepted interventions. However, the low proportion of patients who accepted physical therapy referrals indicates the need for tailored and more personalized approaches. Further research is needed to explore the feasibility and impact of supportive care referral programs for older adults with MM., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options., Patients and Methods: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs., Results: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to αCD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were primarily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications., Conclusion: Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to αCD38 mAb therapy and could help address the unmet clinical need in these high-risk patients., Competing Interests: Acknowledgments Karyopharm funded the study and provided selinexor supply. Sharon Furman-Assaf, supported by funding from Karyopharm, provided drafts and editorial assistance to the authors during the preparation of this manuscript. This work was supported by Karyopharm Therapeutics Inc. Karyopharm Therapeutics was the sponsor of this study and was responsible for study design, the collection of data, analysis of data, interpretation of data, writing of the report, and the decision to submit the paper for publication. The corresponding author had full access to all data and had the final responsibility for the decision to submit for publication with the agreement of all other authors., (Copyright © 2023. Published by Elsevier Inc.)

Multiple myeloma (MM) remains an incurable disease and there is an unmet medical need for novel therapeutic drugs that do not share similar mechanisms of action with currently available agents. Sphingosine kinase 2 (SK2) is an innovative molecular target for anticancer therapy. We previously reported that treatment with SK2 inhibitor opaganib inhibited myeloma tumor growth in vitro and in vivo in a mouse xenograft model. In the current study, we performed a phase I study of opaganib in patients with relapsed/refractory multiple myeloma (RRMM). Thirteen patients with RRMM previously treated with immunomodulatory agents and proteasome inhibitors were enrolled and treated with single-agent opaganib at three oral dosing regimens (250 mg BID, 500 mg BID, or 750 mg BID, 28 days as a cycle). Safety and maximal tolerated dose (MTD) were determined. Pharmacokinetics, pharmacodynamics, and correlative studies were also performed. Opaganib was well tolerated up to a dose of 750 mg BID. The most common possibly related adverse event (AE) was decreased neutrophil counts. There were no serious AEs considered to be related to opaganib. MTD was determined as at least 750 mg BID. On an intent-to-treat basis, one patient (7.7%) in the 500 mg BID dose cohort showed a very good partial response, and one other patient (7.7%) achieved stable disease for 3 months. SK2 is an innovative molecular target for antimyeloma therapy. The first-in-class SK2 inhibitor opaganib is generally safe for administration to RRMM patients, and has potential therapeutic activity in these patients. Clinicaltrials.gov: NCT02757326., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cancer-related cognitive impairment (CRCI) has been largely unstudied in patients with multiple myeloma (MM). This study describes patient-reported cognition over time and patient factors associated with adverse cognitive outcomes in MM., Methods: Participants enrolled in a registry in which they completed a geriatric assessment at study entry, and 3 & 6 months after entry. Cognitive function was assessed using the EORTC QLQ-C30 Cognitive Function subscale, with CRCI defined as scores < 75. Generalized estimating equation (GEE) models were used to fit longitudinal models to investigate differences by group and differences in changes over time by group, with adjustment for time since diagnosis., Results: One hundred and four adults with MM had mean age of 67 years and 30% identified as Black. Patient-reported CRCI was present in 18% of participants at enrollment, 21% at 3 months, and 30% at 6 months. Worse cognitive function was reported in those with impairments in physical function (P = .002), IADLs (P = .02), and performance status (P = .04), as well as in those who were prefrail/frail (P = .02) and depressed (P = .049). Greater cognitive decline over time was observed in patients without CRCI at enrollment (P < .0001) and those with lower levels of education (P = .04)., Conclusion: This is one of the first studies to describe longitudinal changes in patient-reported cognition in patients with MM. Several potentially intervenable factors, including physical function impairment and depression, were associated with worse cognition at study entry, but only baseline CRCI status and education level were predictive of future decline., (Copyright © 2022. Published by Elsevier Inc.)

Background: The plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL)., Patients and Methods: Adults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression., Results: Among 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04)., Conclusions: Patients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs., (© The Author(s) 2022. Published by Oxford University Press.)

Objectives: Findings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80)., Materials and Methods: Adults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0-100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80)., Results: Among 89 adults, the mean age was 69.1 years, 68% were aged ≥65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥14 s and dependence in ≥1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%., Conclusion: Using a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose. The study received support from the North Carolina University Cancer Research Fund. Jensen receives salary support from National Cancer Institute grant T32-CA233419. Wood reports grants from Pfizer, personal fees from Teladoc, and equity in Koneksa Health outside the submitted work., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM)., Methods: The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m 2 ) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib., Results: Thirty-two patients, median prior therapies 4 (range, 1-8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m 2 , and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months., Conclusions: Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM., (© 2021. The Author(s).)

Preclinical studies have demonstrated activity of the oral proteasome inhibitor (PI) ixazomib (IXA) in bortezomib-resistant multiple myeloma (MM) and synergy with immunomodulatory drugs. We therefore conducted a phase I/II study to establish the safety and preliminary efficacy of IXA with pomalidomide (POM) and dexamethasone (DEX) in lenalidomide (LEN)/PI-refractory MM. Dose escalation established a 4 mg dose of POM and IXA and 20/40 mg dose of DEX as the maximum tolerated dose. The phase II portion of the trial was redesigned and started anew after six patients had been randomized to IXA-POM-DEX due to a rapidly changing treatment landscape. Among the 29 evaluable LEN/PI-refractory patients treated with IXA-POM-DEX in phase I/II, the overall response rate (partial response or better) was 51.7% with a median duration of response of 16.8 months (range 56 days to 4.1 years), median progression-free survival of 4.4 months (95% confidence interval [CI]: 3.0-18.4), and median overall survival of 34.3 months (95% CI: 19.2 to not reached). Hematologic, gastrointestinal, and constitutional adverse events were common and consistent with the side-effect profiles of the individual agents. Our results support further evaluation of this all-oral regimen in relapsed/refractory MM., (© 2021 Wiley Periodicals LLC.)

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1-8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab., (© 2021. The Author(s).)

Background: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM., Methods: FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders., Results: Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores., Conclusion: The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach., Trial Registration: This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015., (© 2021. The Author(s).)

Additional therapeutic options are needed for relapsed and refractory multiple myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 50-77]) and a median of four prior regimens (range: 2-14); 85% had refractory disease (lenalidomide [80%]; bortezomib [75%]; lenalidomide and bortezomib [50%]). Patients received a median of six cycles (range: 1-74) of panobinostat (10 or 15 mg), lenalidomide 15 mg, bortezomib 1 mg/m 2 , and dexamethasone 20 mg (pano-RVd). Median follow-up was ~14 months. Six dose-limiting toxicities were reported (mostly hematological); maximum tolerated dose of panobinostat (primary endpoint) was 10 mg. Most common adverse events (AEs) were diarrhea (60%) and peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of patients and included decreased neutrophil (45%), platelet (25%) and white blood cell (25%) counts, anemia (25%) and hypophosphatemia (25%). No treatment-related discontinuations or mortality occurred. In evaluable patients (n = 18), overall response rate was 44%, and clinical benefit rate was 61%. Median duration of response was 9.2 months; progression-free survival was 7.4 months; overall survival was not reached. Pano-RVd proved generally well-tolerated and demonstrated potential to overcome lenalidomide and/or bortezomib resistance.

The spectrum of immunoglobulin paraprotein-associated diseases requiring therapy extends beyond multiple myeloma and AL amyloidosis. Awareness of these is essential in ensuring timely accurate diagnosis and appropriate treatment. As most paraprotein-associated diseases are fairly uncommon, therapeutic decisions must often be made in the absence of data from randomized controlled trials. Treatment is generally directed at the underlying clonal cell population. This review focuses on the spectrum of the less common paraprotein-associated disorders. In most instances, the monoclonal immunoglobulin plays a direct role in the pathophysiology of the disease course; in a select few, the paraprotein may be a disease marker., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Multiple myeloma (MM) is a cancer of older adults with a median age at diagnosis of 70 years. Our study aimed to understand the changes that occurred in geriatric domains and quality of life parameters as older adults underwent treatment for MM over 6-months following initial diagnosis., Methods: This was a secondary analysis of a prospective cohort study of 40 adults aged ≥65 with newly-diagnosed MM who completed the Cancer and Aging Research Group geriatric assessment and the Functional Assessment of Cancer Therapy (General and subscale Gynecologic Oncology Group-Neurotoxicity) quality of life tool at baseline and at 6 months following treatment initiation., Results: Thirty-six participants completed 6-months of follow-up. There was no significant change in geriatric domains, including dependence in instrumental activities of daily living (IADLs). Compared to baseline, mental health improved at 6-months of follow-up (Mental Health Inventory-17 score, median 77.1 versus 84.3 at baseline and 6-months respectively, p < .001). Objective physical performance as measured by the Timed Up and Go test showed a trend towards improvement (12.3 versus 11.0 s, p = .057) and remained stable or improved in almost all (30/32, 93.8%) of the adults using the minimum clinically important difference threshold., Conclusion: From baseline to 6-months of follow-up, older adults with MM showed improvement in mental health but otherwise remained stable with regards to function and overall quality of life. Timed Up and Go Test may provide a dynamic indicator of functional status and needs to be further evaluated in future studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1-2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.

Purpose: We performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG)., Methods: We calculated the difference between a patient's total serum protein and albumin as a point-of-care test for assessing disease status in MM., Results: GG is highly correlated with the level of M-spike, and the change in GG correlates with myeloma treatment response. In addition, fitted linear models were established that allow for the calculation of M-protein level from the GG within hours from blood draw., Conclusion: Our study has important implications in the care of MM, particularly in countries/areas with limited resources.

Objectives: As the aging population grows, interest in applying the concept of frailty to older adults with cancer has increased. This study examines the prevalence of frailty in older patients with multiple myeloma using three frailty models., Methods: In this secondary analysis of a prospective cohort study, 40 adults aged ≥65 with myeloma completed the Cancer and Aging Research Group geriatric assessment within three months of initial diagnosis. Geriatric assessment data was used to categorize patients' frailty status according to three indices: The International Myeloma Working Group (IMWG) Frailty Index, the Revised Myeloma Comorbidity Index (R-MCI), and the Carolina Frailty Index (CFI). Agreement between the indices was examined using Cohen's kappa., Results: Twenty-eight patients were classified as frail by at least one of the models. However, only slight agreement exists on the classification of frailty among the indices, with little concordance among the models (Kappa 0.03-0.12). Only three patients were categorized as frail by all three models., Conclusion: In a cohort of 40 older adults with newly diagnosed multiple myeloma, three frailty indices have differing approaches to operationalizing frailty resulting, in different patients being categorized as frail. Little agreement existed between the models. Further studies are needed to explore the utility of these models in predicting treatment toxicity and prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Lenalidomide, bortezomib, and dexamethasone (RVd) has emerged as a preferred induction therapy in multiple myeloma (MM) in the United States. Due to lenalidomide's teratogenic risk, patients and prescribers must comply with a risk evaluation and mitigation strategy (REMS) program. The REMS program limits dispensing to certain third-party specialty pharmacies, whose average prescription fill times are longer than in-house specialty pharmacies. In practice, a delay in procurement of lenalidomide may mean that patients start therapy with only bortezomib and dexamethasone, delaying the start of more effective triplet therapy. The primary objective of this study is to determine if a delay from start of bortezomib and dexamethasone to start of triplet therapy with lenalidomide impacts rate of achievement of very good partial response (VGPR) after four cycles of RVd., Methods: This was a single-center retrospective review of adults with newly diagnosed MM who received RVd induction therapy at University of North Carolina Medical Center between April 2014 and June 2017. Patients who started lenalidomide ≥10 days after bortezomib comprised the "Delay" group, while those who started lenalidomide concurrently with bortezomib or within 1-9 days after bortezomib comprised the "No Delay" group. The primary outcome was VGPR or better response rate after four cycles of RVd., Results: Thirty-eight patients met inclusion criteria. Nine patients (23.7%) experienced any delay in initiation of lenalidomide, with a mean delay of 7.8 days (range 1-18). Four patients (10.5%) experienced a delay ≥10 days. No patients in the Delay group were of reproductive potential, compared to 8.8% in the No Delay group ( p  = 0.54). VGPR or better response rate did not differ between the Delay and No Delay groups (66.7% vs. 58.8%, p  = 0.79). The mean number of lenalidomide prescriptions generated per RVd cycle was 1.35 (range 1-5, SD 0.74)., Conclusions: This study did not demonstrate an effect on clinical response after delays ≥10 days between bortezomib and lenalidomide initiation. No patients in the delay group were females of reproductive potential, which is the primary target for increased safety behind the REMS program.

Background: Population-based studies suggest that patients with multiple myeloma (MM) have better outcomes when treated at high-volume facilities, but the relative contribution of provider expertise and hospital resources to improved outcomes is unknown. This study explored how treating facility, individual provider volume, and patient-sharing between MM specialists and community providers influenced outcomes for patients with MM., Patients and Methods: A state cancer registry linked to public and private insurance claims was used to identify a cohort of patients diagnosed with MM in 2006 through 2012. Three multivariable Cox models were used to examine how the following factors impacted overall survival: (1) evaluation at an NCI-designated Comprehensive Cancer Center (NCICCC), (2) the primary oncologist's volume of patients with MM, and (3) patient-sharing between MM specialists and community oncologists., Results: A total of 1,029 patients diagnosed with MM in 2006 through 2012 were identified. Patients who were not evaluated at an NCICCC had an increased risk of mortality compared with those evaluated at an NCICCC (hazard ratio [HR], 1.50; 95% CI, 1.21-1.86; P<.001). Compared with patients treated by NCICCC MM specialists, those treated by both low-volume community providers (HR, 1.47; 95% CI, 1.14-1.90; P<.01) and high-volume community providers (HR, 1.29; 95% CI, 1.04-1.61; P<.05) had a higher risk of mortality. No difference in mortality was seen between patients treated by NCICCC MM specialists and those treated by the highest-volume community oncologists in the ninth and tenth deciles (HR, 1.08; 95% CI, 0.84-1.37; P=.5591). Patients treated by community oncologists had a higher risk of mortality regardless of patient-sharing compared with patients treated by MM specialists (eg, community oncologist with a history of sharing vs NCICCC MM specialist: HR, 1.49; 95% CI, 1.10-2.02; P<.05)., Conclusions: Findings of this study add to the accumulating evidence showing that patients with MM benefit from care at high-volume facilities, and suggest that similar outcomes can be achieved by the highest-volume providers in the community.

Background: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options., Methods: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point., Results: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients., Conclusions: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.)., (Copyright © 2019 Massachusetts Medical Society.)

Background/objectives: The incidence of myeloma in older adults is increasing, yet little is known about geriatric impairments in these patients. We aimed to examine the prevalence of geriatric impairments in older adults with myeloma and the association between geriatric assessment and autologous stem cell transplant eligibility., Design: Prospective cohort study., Setting: Two academic medical centers., Participants: A total of 40 adults 65 years and older with newly diagnosed myeloma were enrolled., Measurement: Participants completed a primarily self-administered geriatric assessment, including measures of functional status, comorbidities, polypharmacy, psychosocial status, social support, quality of life, cognition, and physical performance. Outcomes were autologous stem cell transplant eligibility and receipt., Results: Forty patients enrolled; their mean age was 71 years. Geriatric impairments were common: 62% reported dependence in one or more instrumental activities of daily living (IADL), 76.9% had polypharmacy (four or more medications), and 47.5% had one or more comorbidities. Median time on the Timed Up and Go was 13.3 ± 4.9 seconds. Those considered candidates for autologous stem cell transplant (N = 26) were younger, with fewer comorbidities, better performance status, and faster performance on the Timed Up and Go test. Factors independently associated with receiving autologous stem cell transplant (N = 21) included age and IADL dependence., Conclusion: Impairments in geriatric domains are common in this population, even among those considered to have a good performance status. Geriatric assessment domains are associated with both transplant eligibility and receipt. J Am Geriatr Soc 67:987-991, 2019., (© 2018 The American Geriatrics Society.)

Background: Serum free light chain (FLC) immunoglobulins are key biomarkers that aid in the diagnosis, prognosis and assessment of treatment response in patients with plasma cell disorders (PCD). Here we investigated the transference of manufacturer's reported κFLC, λFLC and κ to λ FLC reference intervals (RI) and established de novo FLC RI and diagnostic ranges on four instruments at three academic medical centers. In addition, we also compared the classification of patient FLC results using manufacturer's versus established RIs and diagnostic ranges., Methods: CLSI EP28-A3C protocol was applied to investigate transference and establishment of FLC reference intervals on the cobas (Roche), Immage (Beckman), Optilite and SPA Plus (Binding Site). Serum κ FLC and λ FLC were measured in reference sera (N = 126) with estimation of central 95% RIs and FLC ratio diagnostic range (total range). Frequencies (%) in patient FLC results (N > 380 per institution) classified above, below or within manufacturer's versus established FLC RI were compared., Results: Three of four instrument platforms did not exhibit acceptable transference of manufacturer's reported κ FLC RI. The manufacturer's reported FLC total diagnostic range did not encompass all values observed in reference sera for any of the four platforms evaluated. Established FLC ratio diagnostic ranges reduced the frequency of patient results classified above range for three of four platforms evaluated., Conclusions: Transference of manufacturer's reported FLC RIs may be inappropriate for select instrument platforms. De novo establishment of FLC RIs specific to instrument platform is highly recommended in order to assure correct patient result classification., (Published by Elsevier Inc.)

Background: With the expanding armamentarium of therapeutic agents for multiple myeloma (MM), it is important to identify any undertreated patient populations to mitigate outcome disparities., Materials and Methods: We extracted the data for all plasma cell myeloma cases (International Classification of Disease for Oncology, third revision [ICD-O-3] code 9732) in the Surveillance, Epidemiology, End Results (SEER)-Medicare database from 2007 to 2011. The ICD-O-3 histologic code 9732 captures both active MM and smoldering/asymptomatic myeloma. We defined active MM as either claims indicating receipt of treatments approved for MM or ICD-9 codes for MM-defining clinical features, referred to as the CRAB criteria (calcium [elevated], renal failure, anemia, bone lesions). Multivariate logistic regression was performed to determine the variables that were independently associated with receipt of no treatment., Results: Of the initial 4187 patients included in the present study, 373 had no claims indicating receipt of treatments approved for MM and had no ICD-9 codes associated with the CRAB criteria and were excluded from the analyses. Of the 3814 patients with active MM, 1445 (38%) did not have any claims confirming that they had received systemic treatment. Older age, poor performance indicators, comorbidities, African-American race, and lower socioeconomic status, including enrollment in Medicaid, were statistically significant factors associated with the receipt of no systemic treatment., Conclusions: In the present retrospective study of data from the SEER-Medicare database, we found that age, health status, race, and socioeconomic status were associated with receipt of MM treatment. These factors have previously been linked to reduced usage of specific treatments for MM, such as stem cell transplantation. To the best of our knowledge, however, ours is the first study to show their association with the receipt of any MM therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression-free survival (PFS) of older patients was non-inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5-year increase in age was ≥1.05; the alternative (non-inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86-1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94-1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant-related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD ("VCD-Lite") in such vulnerable adults with newly diagnosed MM (NDMM)., Materials and Methods: Subjects with NDMM and a high risk of therapy-related toxicity due to factors above received bortezomib 1.3mg/m 2 subcutaneously, cyclophosphamide 300mg/m 2 and dexamethasone 40mg orally, all on days 1, 8, and 15 of a 28day cycle for eight cycles, followed by indefinite, alternating bortezomib and lenalidomide maintenance. Toxicity, overall response rate (ORR), progression-free and overall survival (PFS and OS) were determined. The Cancer and Aging Research Group geriatric assessment (CARG GA) was administered at baseline in an exploratory manner as a predictor of severe toxicity., Results: 14 patients went on the study, which was closed early due to slow accrual. Intention-to-treat ORR was 64%. 64% of patients experienced grade ≥3 adverse events, the majority of which were unlikely therapy-related. Median PFS was 24.2months and OS 29.7months, with 14%, 36% and 29% of patients discontinuing study drugs due to toxicity, MM progression and other reasons respectively. Baseline CARG GA was successfully completed by all subjects but one., Conclusion: VCD-Lite is a viable option for vulnerable adults with NDMM. CARG GA is feasible. Further studies to optimize therapy and to explore CARG GA as a toxicity predictor are vital., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are plasma cell disorders of aging. The landscape of the diagnosis and management of MM and MGUS are rapidly changing. This article provides an updated understanding of the clinical presentation, evaluation, diagnosis, and management of older adults with MM and MGUS. Because most oncology providers are not formally trained in geriatric medicine, geriatricians play a key role in providing oncologists with a broader understanding of patient health status in the hope of improving outcomes for older adults with MM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively., (© 2014 Wiley Periodicals, Inc.)

Background: The safety and feasibility of the symptom-limited cardiopulmonary exercise test (CPET) and the 6-minute walk test (6MWT) has not been rigorously tested in patients with multiple myeloma (MM) after high-dose chemotherapy with autologous stem cell transplantation (ASCT), nor have correlations with patient-reported outcomes (PROs) been explored., Patients and Methods: We undertook CPET, 6MWT, and PRO assessments using standardized measurements and questionnaires in patients with MM in remission after ASCT., Results: A total of 22 patients who were a median of 17 months after ASCT underwent assessment. No severe adverse events were observed. Exercise capacity, measured during CPET as the peak oxygen consumption, was 17.5 ± 5.9 mL/kg/min, the equivalent of 38% ± 18% less than that for age- and sex-predicted sedentary normative values. During the 6MWT, the mean 6-minute walk distance was 500 m, or 25% ± 13% less than the predicted values. Additional analysis using Pearson's correlation revealed no significant univariate associations between exercise or functional capacity and any PROs., Conclusion: Patients with MM have marked and significant reductions in quantitative measures of physical function for years after the initial therapy, although that did not correlate with PROs in the present pilot study. Larger prospective studies are required to determine the clinical ramifications of these findings and to mechanistically dissect them, as well to test interventions aimed at mitigating them., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Multiple myeloma (MM) is disproportionately diagnosed in older adults; with the aging of the population, the number of older adults diagnosed with MM will increase by nearly 80% in the next two decades. Duration of survival has improved dramatically over the last 20 years, but the improvements in older adults have not been as great as those in younger adults with MM., Methods: In this article, we address treatment approaches in older adults who are eligible for and those ineligible for high-dose therapy with autologous stem-cell transplantation as well as supportive care considerations and the potential role for geriatric assessment in facilitating decision making for older adults with MM., Results: The evidence from recent studies demonstrates that combinations of novel and conventional antimyeloma agents result in improved response rates and, in some cases, improved progression-free and overall survival. However, some older adults are particularly vulnerable to toxicities of therapy and discontinuation of therapy and, consequently, they have poorer survival. In addition, older adults may prioritize other outcomes of therapy, such as quality of life, over more conventional end points such as disease response and duration of survival. Geriatric assessment can facilitate risk-stratification of older adults at greater risk for adverse events from therapy and aid in personalizing therapy for vulnerable or frail older adults., Conclusion: Survival in older adults with MM is improving with novel therapeutics, but efficacy must be balanced with risk of toxicity of therapy and maintenance of quality of life. Novel instruments such as geriatric assessment tools may facilitate these aims.

Major improvement milestones in the treatment of patients with multiple myeloma (MM) include the introduction of the melphalan/prednisone combination in the 1960s, high-dose chemotherapy supported by autologous stem cell transplant in the 1980s, and the more recent introduction of the novel agents thalidomide, lenalidomide, and bortezomib. Historically, age and eligibility for autologous stem cell transplantation were the primary basis for treatment selection, but, from a biologic standpoint, MM therapy was "one size fits all," in that therapy was not tailored based on molecular or other features that define subtypes of MM. Recently, novel therapies have extended overall survival for the broad spectrum of patients with myeloma. Moreover, newer data demonstrate that novel therapies may ameliorate the prognostic impact of predictors of high risk and poor outcome in MM, which suggests that patients with MM and with high-risk disease should receive novel agents. Such approaches may constitute nascent steps toward individualized therapy, ie, the selection of highly effective therapies based on specific features exhibited by an individual patient's MM. However, prospective data that demonstrate the validity of these approaches are lacking. Definitive, multi-institutional clinical trials are required before redefining standards of myeloma care based on this approach., (Copyright © 2011. Published by Elsevier Inc.)

Purpose: Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) comprise heterogeneous disorders with incompletely understood molecular defects and variable clinical features. We performed gene expression profiling (GEP) with microarray data to better dissect the molecular phenotypes, sensitivity to particular chemotherapeutic agents, and prognoses of these diseases., Methods: Using gene expression and clinical data from 877 patients ranging from normal plasma cells (NPC) to relapsed MM (RMM), we applied gene expression signatures reflecting deregulation of oncogenic pathways and tumor microenvironment to highlight molecular changes that occur as NPCs transition to MM, create a high-risk MGUS gene signature, and subgroup International Staging System (ISS) stages into more prognostically accurate clusters of patients. Lastly, we used gene signatures to predict sensitivity to conventional cytotoxic chemotherapies among identified clusters of patients., Results: Myc upregulation and increasing chromosomal instability (CIN) characterized the evolution from NPC to RMM (P < .0001 for both). Studies of MGUS revealed that some samples shared biologic features with RMM, which comprised the basis for a high-risk MGUS signature. Regarding MM, we subclassified ISS stages into clusters based on shared features of tumor biology. These clusters differentiated themselves based on predictions for prognosis and chemotherapy sensitivity (eg, in ISS stage I, one cluster was characterized by increased CIN, cyclophosphamide resistance, and a poor prognosis)., Conclusion: GEP provides insight into the molecular defects underlying plasma cell dyscrasias that may explain their clinical heterogeneity. GEP also may also refine current prognostic and therapeutic models for MGUS and MM.

There is a lack of consensus on therapy sequencing in previously treated multiple myeloma, particularly after anti-B-cell maturation antigen (BCMA) therapy. Earlier reports on selinexor (X) regimens demonstrated considerable efficacy in early treatment, and after anti-BCMA-targeted chimeric antigen receptor-T cell therapy. Here, we present data from 11 heavily pretreated patients who predominantly received BCMA-antibody-drug conjugate therapy. We observe that X-containing regimens are potent and achieve durable responses with numerically higher overall response and clinical benefit rates, as well as median progression free survival compared to patients prior anti-BCMA therapies, despite being used later in the treatment course. In an area of evolving unmet need, these data reaffirm the efficacy of X-based regimens following broader anti-BCMA therapy.

PURPOSE Residents of communities facing social vulnerability (eg, poverty) have limited access to clinical trials, leaving them susceptible to experiencing poor health outcomes. We examined the association between North Carolina county-level social vulnerability and available multiple myeloma (MM) trials. METHODS Using a novel data linkage between ClinicalTrials.gov, the 2019 American Community Survey, and the Centers for Disease Control and Prevention's Social Vulnerability Index, we investigated at the county level (1) availability of MM trial sites and (2) the relationship between Social Vulnerability Index and MM trial site availability using logistic regression. RESULTS Between 2002 and 2021, 229 trials were registered across 462 nonunique trial sites in 34 counties. Nearly 50% of trial sites were in academic medical centers, 80% (n = 372) of all trials were industry-sponsored, 60% (n=274) were early-phase, and 50% (n5232) were for patients with relapsed or refractory MM. Counties with low as opposed to high poverty rates had six times greater odds of having ≥1 MMtrial sites (odds ratio [OR], 5.60; 95% CI, 1.85 to 19.64; P = .004). Counties with the lowest percentage of Black Indigenous Persons of Color and non-native English speakers had 77% lower odds (OR, 0.23; 95% CI, 0.07 to 0.69; P = .011) of having ≥ 1 trial sites. The effect remained significant after accounting for the presence of five academic medical centers (n = 95; OR, 0.18; 95% CI, 0.05 to 0.6; P = .008) and adjustment for metropolitan, suburban, or rural status (OR, 0.25; 95% CI, 0.07 to 0.81; P = .025). CONCLUSION Counties with the lowest poverty rates had more MM trial sites, whereas those with the lowest percentage of Black Indigenous Persons of Color populations had fewer MM trial sites. Multilevel efforts are needed to improve the availability and access to trials for socially vulnerable populations. [ABSTRACT FROM AUTHOR]

Older adults with plasma cell disorders (PCDs) experience cognitive dysfunction that may be attributable to the disease and associated therapies. Yet, this has seldom been reported in the literature. Our objectives were to describe cognitive function (objective and patient-reported) in adults with PCDs and to explore clinical correlates of cognitive impairment. Participants completed a geriatric assessment between March 2018 and February 2020. Cognitive function was evaluated using two objective measures – Montreal Cognitive Assessment (MoCA, cutpoint <26) and Blessed Orientation Memory Concentration Test (BOMC, cutpoint >4) – and two patient-reported outcome (PRO) measures – Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF, cutpoint <45) and European Organization for Research and Treatment of Cancer Cognitive Functioning subscale (EORTC-CF, cutpoint <75). Spearman correlations examined relationships among these measures and log binomial regression was used to examine characteristics associated with cognitive impairment, as defined by the MoCA and PROMIS-CF measures. Among 86 participants with a mean age of 69 (range: 46–91), the prevalence of cognitive dysfunction was between 20% (BOMC) and 63% (MoCA). There was moderate correlation among objective measures (r = 0.51, p < 0.0001), moderate to high correlation among PRO measures (r = 0.69, p < 0.0001), but no correlation between objective and PRO measures. Factors associated with objective impairment included ≤ high school education (RR 1.46, p = 0.009), living alone (RR 1.42, p = 0.02), relapsed/refractory disease (RR 1.39, p = 0.04), empirically de-intensified induction therapy (RR 1.62, p = 0.008), frailty (RR 1.49, p = 0.04), and peripheral vascular disease (RR 1.54, p = 0.002). Factors associated with PRO impairment included social isolation (RR 3.43, p = 0.003), depression (RR 3.30, p = 0.004) and anxiety (RR 4.43, p = 0.0002), frailty (RR 3.60, p = 0.02), falls in the previous 6 months (RR 2.53, p = 0.02), and deficits in physical function (RR 4.44, p = 0.01). Older age was not associated with either objective or PRO impairment. Cognitive impairment, using objective and PRO screening measures, was relatively common in adults with PCDs. Cancer-related factors and medical comorbidities were associated with objective cognitive impairment whereas psychosocial and functional factors were associated with PRO impairment. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus mucocutaneous ulcers (EBV MCU) are B‐cell lymphoproliferative disorders associated with immunosuppression. We report EBV MCU in a multiple myeloma patient on lenalidomide maintenance after stem cell transplant that resolved with decreased immunosuppression. Furthermore, the subsequent development of classical Hodgkin lymphoma suggests an underlying predisposition to EBV‐driven lymphoproliferative disorders. [ABSTRACT FROM AUTHOR]

Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma. [ABSTRACT FROM AUTHOR]

Purpose: The distinction of patients with symptomatic multiple myeloma (MM) from those with smoldering MM poses a challenge for researchers who use administrative databases. Historically, researchers either have included all patients or used treatment receipt as the distinguishing factor; both methods have drawbacks. We present an algorithm for distinguishing between symptomatic and smoldering MM using ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes for the classic defining events of symptomatic MM commonly referred to as the CRAB criteria (hypercalcemia, renal impairment, anemia, and bone lesions). Patients and Methods: SEER-Medicare–linked data from 4,187 patients with MM diagnosed between 2007 and 2011 were used for this analysis. Results: Eighty-four percent had ICD-9-CM codes consistent with CRAB criteria, whereas only 57% received treatment. Overall survival of patients with symptomatic MM defined as receipt of treatment was 32.3 months versus 26.6 months for the overall population and 22.9 months for patients with symptomatic MM defined by CRAB criteria. Conceptually, removal of patients with smoldering MM should result in a reduction in overall survival; however, the cohort of patients who received treatment tended to be younger and healthier than the overall population, which could have skewed the results. Conclusion: The algorithm we present resulted in a larger and more representative sample than classification by treatment status and reduced potential bias that could result from including all patients with smoldering MM in the analysis. Although this study was performed using the SEER-Medicare database, the methodology was broad enough that the algorithm could be extended to additional claims-based data sets with relative ease. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second most common hematologic malignancy in the US. It is typically characterized by production of large amounts of defective immunoglobulin (Ig). Diagnosing MM and monitoring treatment response, including eventual relapse, are largely based on sequential measurements of Ig. However, a small subset of MM called non-secretory multiple myeloma (NSMM) produces no detectable Ig. This subset of true NSMM has become even smaller over time, as the advent of the serum free light chain assay has resulted in the majority of NSMM patients being recategorized as light-chain MM - that is, MM cells that produce only the light-chain component of Ig. True forms of NSMM, meaning MM that secretes no monoclonal proteins whatsoever, constitute a distinct entity that is reviewed; definition of NSMM using current detection methods, discuss the biology underpinning NSMM development, and share recommendations for how NSMM should be managed clinically with respect to detection, treatment, and monitoring. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) in patients aged greater than 80 years poses an increasingly common challenge for oncology providers. A multidisciplinary workshop was held in which MM-focused hematologists/oncologists, geriatricians, and associated health-care team members discussed the state of research for MM therapy, as well as themes from geriatric medicine that pertain directly to this patient population. A summary statement of our discussions is presented here, in which we highlight several topics. MM disproportionately affects senior adults, and demographic trends indicate that this trend will accelerate. Complex issues impact cancer in seniors, and although factors such as social environment, comorbidities, and frailty have been well characterized in nononcological geriatric medicine, these themes have been inadequately explored in cancers such as MM, despite their clear relevance to this field. Therapeutically, novel agents have improved survival for MM patients of all ages, but less so for seniors than younger patients for a variety of reasons. Lastly, both MM- and treatment-related symptoms and toxicities require special attention in senior adults. Existing research provides limited insight into how best to manage these often complex patients, who are often not reflected in typical clinical trial populations. We hence offer suggestions for clinical trials that address knowledge gaps in how to manage very old and/or frail patients with MM, given the complicated issues that often surround this patient population. [ABSTRACT FROM AUTHOR]