Young Multiple Myeloma Patients Research Articles

Disease Characteristics and Outcomes of 493 Young Myeloma Patients Treated With Modern Therapies: A Canadian Myeloma Research Group Database Study.

Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature. We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022. The median age was 46 years old (range: 25.6-50). Most patients fell into the R-ISS II category (72.7%), and 24.1% had high-risk cytogenetics. The majority of patients (89.9%) received a proteasome inhibitor-based first-line treatment, 92.1% received a stem cell transplant, and 65.6% had maintenance therapy post-autologous stem cell transplant (ASCT). Median follow-up from initial treatment to patients' last follow-up was 48.5 (range: 0-155) months. Median progression-free survival (PFS) was 45.0 months (95% CI: 40.2-50.0). Maintenance therapy post-ASCT improved median PFS to 52.3 months (95% CI: 43.1-68.2), compared to 23.6 months (95% CI: 20.0-34.8) without maintenance[p < 0.001]. Although the overall survival has not yet been reached in this young population, our reported median PFS of only 45 months highlights the urgent need to develop innovative treatments to induce more profound and durable responses.

Pathogenic germline variant discovery in plasma cell disorders: Insights from genetic counseling referrals and testing.

10619 Background: Our research has shown that 10% of multiple myeloma (MM) patients harbor pathogenic or likely-pathogenic germline variants (PGVs) in cancer predisposition genes, with a significant enrichment observed in BRCA1/2 genes. PGVs are notably more common in younger MM patients and those with a personal or familial cancer history. This study presents our experience in referring plasma cell disorder (PCD) patients at increased risk for carrying PGVs, due to either clinical history or suspicious tumor NGS findings, for genetic counseling and subsequent germline testing. Methods: This retrospective study reviewed patient records from our institution's PCD clinic, focusing on those referred for a genetic evaluation between 2020 and 2024 due to suspected cancer predisposition. We compiled demographic and clinical data for these patients, reasons for referral, and cancer history of patients and their families. The uptake of germline testing, identified mutations, and subsequent recommendations for advanced cancer surveillance and prevention, including cascade testing, were also analyzed. Germline testing utilized targeted hereditary cancer panels from five companies and was conducted on DNA samples extracted from peripheral blood, saliva/buccal swabs, or skin biopsies. Results: 52 PCD patients underwent a genetic evaluation and were included in this review, comprising 31 MM, 9 smoldering MM, and 12 MGUS cases. Median age at the time of referral was 63, and 54% of patients were female. Racial composition was 62% White, 15% Black/African-American, 12% Hispanic, 2% Asian, with 10% undisclosed. 8 patients were referred due to suspicious findings in tumor NGS, while the rest were referred due to clinical suspicion. A personal history of cancer was reported by 19 patients (37%), and 49 had a first- or second-degree relative with cancer (94%). 38 patients (73%) underwent germline testing, of which 15 (39%) harbored PGVs (11 had MM, 4 had smoldering MM). 8 PGV carriers had well-established founder variants. The remaining 7 had PGVs in genes including BRCA2 (n=3), PALB2 (n=1), BLM (n=1), SMAD4 (n=1) and NTHL1 (n=1). Of note, all 8 referred for suspicious findings in tumor NGS were confirmed to harbor PGVs. All PGV-positive patients were recommended for cascade testing and enhanced cancer screening. Conclusions: Our findings indicate a 39% PGV detection rate in PCD patients referred for genetic evaluation, underscoring the potential benefit of implementing screening guidelines in this population. PGV detection led to recommendations for intensified surveillance and cascade testing in all cases, impacting both patients and their families. The discovery of BRCA2PGVs in 20% (3/15) of cases reinforces its potential role as a predisposition gene in MM, corroborating our prior findings.

Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Young and High-Risk Multiple Myeloma Patients

Objective: With the new therapeutic agents developed over last decades, the median survival of patients with multiple myeloma has approached 10 years. However, 15-20% of patients who are classified as High-risk multiple myeloma (HRMM) patients still have a median survival of less than 3 years, which leaves room for improvements. Simultaneously, transplantation related mortality (TRM) has been decreasing since progress of supportive care during these years. Thus, this study aims to evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young high-risk multiple myeloma (HRMM) patients and to conduct statistical analysis of various prognostic factors in the new era. Method: This retrospective study analyzed clinical data from 14 young multiple myeloma patients with high-risk cytogenetic abnormalities or high-risk disease biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology &amp; Blood Diseases Hospital between November 2016 and November 2022. Results: There were 7 males and 7 females involved in this study, with a median age of 39.5 (31- 50) years at the time of transplantation. The median number of treatment lines before transplantation was 2 (1-6). Before transplantation, 42.9% (6/14) of the patients did not achieve complete remission (CR), with 35.7% (5/14) of the patients performing MRD (+). After transplantation, all patients could be evaluated for treatment response, in which the overall response rate was 100% (14/14). All 14 patients successfully underwent transplantation, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute graft-versus-host disease (GVHD) of grades II-IV occurred in 5 patients (35.7%), and 2 patients (14.3%) developed moderate to severe chronic GVHD. The median follow-up time after transplantation was 18.93 (4.1-72.53) months, with the 2-year TRM of 7.1% (95%CI 0-19.7%) and the expected 2-year overall survival (OS) rate of 92.9% (95% CI 80.3-100%). Meanwhile, the expected 1-year and 2-year progression-free survival rates were 85.7% (95% CI 69.2-100%) and 45.7% (95% CI 20.9-99.9%), respectively, and the presence of chronic GVHD might influence the outcome positively. Conclusion: Allogeneic hematopoietic stem cell transplantation is an effective treatment to improve the prognosis of young and high-risk multiple myeloma patients.

МНОЖЕСТВЕННАЯ МИЕЛОМА: ОСОБЕННОСТИ ТЕЧЕНИЯ И ОТВЕТА НА ТЕРАПИЮ У ПАЦИЕНТОВ РАЗНЫХ ВОЗРАСТНЫХ ГРУПП

Background: Multiple myeloma (MM) remains an incurable disease with the development of relapses, sometimes with an uncontrolled course leading to death regardless of the age of the patient. The use of new schemes and methods of treatment has not only significantly improved outcomes in younger MM patients but also improved the quality of life and survival in people over 65 years of age. Objective: to determine the clinical features of the course of the disease and response to therapy in patients of different age groups with newly diagnosed multiple myeloma. Material and Methods: An analysis of the data of 139 patients with newly diagnosed MM was carried out. The median follow-up was 25 months, with a maximum of 58 months. Patients were divided into study groups depending on age at the time of diagnosis: the first group - age up to 65 years (n=65); the second group - age from 65 years and older (n=74). The material of the study was clinical and anamnestic data, the results of laboratory blood tests: biochemical analysis and immunochemical analysis. All the patients underwent the whole body CT scan, diffusely weighted whole body MRI and bone marrow aspiration biopsy with immunophenotypic study. As an induction therapy, according to international recommendations, courses of chemotherapy were used using various regimens containing bortezomib, depending on age and comorbidity. Results. The MM variant with IgA secretion occurred 1.76 times more often in the first group (p=0.128). In the first group hypercalcemia was somewhat more common (2.4 times, p=0.099) and an excess of LDH levels (2.9 times, p=0.072). In contrast, the presence of infectious complications (by 1.2 times, p=0.392), excess of the level of β2-microglobulin &gt; 3 mg/l (by 1.6 times, p=0.086) and kidney damage (by 1.45 times, p=0.037) were more common in the second group, and in the latter case the differences were statistically significant. Disease stage (p=0.0001), excess of β2 microglobulin level (p=0.004), excess of LDH level (p=0.03), presence of anemic syndrome (p=0.003), hypercalcemia (p=0.02), presence of infectious complications (p=0.01) at the time of diagnosis were predictors of worse survival in the general group of MM patients. Conclusion. The active use of new therapeutic strategies and regimens improves treatment outcomes not only in patients under 65 years of age, but also in older patients. New studies are needed to identify prognostic factors in individuals of different age groups in order to start personalized therapy and improve treatment outcomes.

Disease Characteristics and Outcomes of 504 Young Patients Diagnosed with Multiple Myeloma Treated with Modern Therapies in Canada

Background:Multiple myeloma (MM) mostly affects older adults. Although representing around 10% of all cases, patients ≤ 50 years old suffer from the highest number of years lost due to their disease. MM in young patients occurs during their most productive years of life, resulting in a significantly higher personal, familial, professional, and economic burden. Young MM patients are currently underrepresented in clinical trials due to small numbers overshadowed in cohorts of older patients. Their disease characteristics and outcomes following modern treatments remain poorly understood (Tanguay M et al., Current Oncol 2023). The purpose of this study is to report disease characteristics, treatments, and outcomes of young MM patients treated in Canada. Methods:This is a retrospective study using the Canadian Myeloma Research Group Database, which is a repository of real-world patient data reflecting 17 of the major MM academic centers across Canada. All patients 18-50 years old with newly diagnosed MM between January 1, 2010 and July 1, 2022 were included. High-risk (HR) cytogenetics were defined as either del17p, t(4;14) or t(14;16). Survival analyses were performed using the Kaplan-Meier method. Results:Among the 6,604 patients newly diagnosed with MM during the study period, 504 (7.6%) were aged between 18-50 years, and included in this analysis. Within this young group, 87 (17.3%) were 18-40 years old and 417 (82.7%) were between 41-50 years. MM was diagnosed in 301 (59.7%) patients between 2010 to 2015, and in 203 (40.3%) patients between 2016 to 2022. The median age at diagnosis was 45.9 years (range 25.6 to 50). Male patients represented 57.7% of the cohort. IgG was the most common isotype in 251 (49.8%) cases, while 115 (22.8%) patients had light chain disease. In 375 patients with available data, 16% were R-ISS 1, 73.1% R-ISS 2, and 10.9% R-ISS 3. Lytic lesions, elevated creatinine, anemia, hypercalcemia, and high LDH were respectively present in 46.8%, 15.5%, 44%, 18.8%, and 18.7% of patients. HR cytogenetics were present in 23.7% of patients, with del17p in 11.5%, t(4;14) in 14.9%, and t(14;16) in 5.1%; while 1q+ and del1p were detected in 27.9% and 15.3%, respectively. Twelve (2.4%) patients were diagnosed with plasma cell leukemia. First-line treatment was proteasome inhibitor (PI)-based in 462 (91.7 %) and immunomodulatory (IMiD) agent-based in 7 (1.4 %); 18 (3.6%) received both a PI and an IMiD and 17 (3.4%) were treated with other modalities. Among all patients, 453 (89.9%) underwent autologous stem cell transplant (ASCT) during their disease course. Some patients did not receive ASCT for the following reasons: early death before ASCT in 10 (2%) cases, lost to follow-up prior to ASCT in 13 (2.6%) cases, deemed ineligible for ASCT or patient declined in 24 (4.8%) cases, and participation in a clinical trial not involving ASCT in 1 (0.2%) case. Out of the entire cohort, allogeneic-SCT (allo-SCT) was performed in only 11 patients (2.2%), including 3 (0.6%) who received allo-SCT alone without ASCT. Among patients who received maintenance post ASCT, 93.6% were treated with a lenalidomide-based regimen. Median duration of the different maintenance treatments was 21.2 months. With a median follow-up of 51.9 months (range 0.9 to 154), median PFS (progression-free survival) was 55.4 months (95% CI 49.1-70.2), while median OS (overall survival) was not reached. The 5-year OS and PFS were 78% (95% CI 74-82) and 48% (95% CI 43-53), respectively, whereas the 10-year OS and PFS were 64% (95% CI 58-71) and 28% (95% CI 22-35), respectively (Figure 1a). Median PFS for patients with any HR cytogenetics was 37.9 months (95% CI 29.6-62.8) vs 64.5 months (95% CI 50.6-80.7) for patients with standard-risk cytogenetics (p=0.004) (Figure 1b). We observed no difference in disease characteristics, treatments, and outcomes after comparing cohorts aged 18-40 years old vs 41-50 years old. Conclusions: This is among the largest real-world cohorts of young MM patients ≤ 50 years old treated with modern therapies ever reported. Most patients were R-ISS 2 (73.1%), 23.7% had known HR cytogenetics, and the majority (91.7%) received a PI-based first-line treatment. Outcomes of specific subgroups are under analysis and will be presented. Although the OS was not yet reached in this young population, the median PFS of only 55.4 months highlights the urgent need to develop more effective treatments to induce deeper and more durable responses.

Young and Distinct: Clinical Characteristics and Outcomes of Patients 50 or Younger with Multiple Myeloma

Introduction: Multiple Myeloma (MM) presents at a median age of 69. Patients age 50 or younger represent only 10% of diagnoses and are less well-characterized. Some studies have suggested that younger MM patients are more likely to present with lytic lesions, be IgD subtype, have high-risk cytogenetics, and have relatively improved survival. We aimed to characterize this understudied population in the modern era. Methods: We conducted a retrospective chart review of patients age &amp;lt;50 meeting IMWG criteria for symptomatic MM treated across our institution's cancer center network between 2010 and 2023. Overall survival was defined as time in months from diagnosis to last follow-up or death. Time to relapse after transplant was captured. Results: We identified 97 younger MM patients, with a median age of 44 (range 26-50). Males and females represented 50.5% and 49.5% of cases respectively. Complete demographics are listed in the table. The most common MM subtype was IgG Kappa (40%), and 23% had light chain-only disease. Incidentally found cases, defined as abnormalities on imaging or labs ordered for another reason, represented 11% of cases. 61% of patients presented with a skeletal issue such as bone pain and/or pathologic fracture. Presenting features are described in the table. At time of diagnosis, 77% of patients were found to have lytic lesions. Few patients had previously identified MGUS (3%) or smoldering MM (5%). Regarding cytogenetics, 18% had one or more high-risk features. The most common frontline treatment was VRD. As shown in the table, 66% and 29% received 3 and 4 drug induction regimens respectively. Of note, 91% were referred for autologous stem cell transplant (ASCT), and 72% proceeded. 4 patients were deceased at the time of analysis. Survival for the entire population was 95.9% at a median follow up time of 65.5 months. In the patients who underwent ASCT, 41.2% relapsed with median progression-free survival of 57 (44-71) months. Conclusions: MM patients age &amp;lt;50 were found to be distinct from the known characteristics of the general population in several notable ways. There was equipoise among demographic features, with a nearly equivalent prevalence in males and females, and similar median ages across racial groups. We found a greater enrichment of light chain disease than expected, but less renal dysfunction at presentation. IgD subtype does not appear increased in this population. Younger patients do not appear more likely to have high risk cytogenetics. Lastly, survival for younger patients was higher compared to the reported 5-year survival of MM, which may be explained by the finding that these patients were treated primarily with triplet or quadruplet anti-myeloma regimens and often proceeded to ASCT.

Diagnosing and treating young multiple myeloma patients. Experience from a tertiary-care center in Mexico

Diagnosing and treating young multiple myeloma patients. Experience from a tertiary-care center in Mexico

Outcomes of young adults (aged ≤ 40 years) with newly diagnosed multiple myeloma after up-front autologous stem cell transplant.

Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto-HCT). In this single-centre analysis, we included 117 younger patients, with a median age of 37 years (range 22-40) at transplant. Seventeen (15%) patients had high-risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post-transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow-up for survivors of 72.6 months (range 0.9-238.0), median PFS and OS were 43.1 months (95% CI 31.2-65.0) and 146.6 months (95% CI 100.0-208.1) respectively. Patients who underwent auto-HCT after 2010 had better median PFS (84.9 months vs. 28.2 months, p < 0.001) and OS (NR vs. 91.8 months, p < 0.001) compared with those transplanted earlier. In multi-variate analysis, achieving ≥CR as best post-transplant response was associated with improved PFS (HR [95% CI] 0.55 [0.32-0.95], p = 0.032), while achieving ≥VGPR was predictive of superior OS (0.32 [0.16-0.62], p < 0.001). Three patients (3%) developed a second primary malignancy. Younger MM patients had durable survival after auto-HCT, which further improved after the availability of novel anti-myeloma drugs in recent years. Depth of response following transplant remains a key predictor of survival.

Determinants of overall survival of young adults with multiple myeloma: A National Cancer Database (NCDB) analysis of years 2004-2017.

8052 Background: There is paucity of real-world data on the outcomes of younger patients with multiple myeloma (MM). In this IRB approved retrospective analysis, the NCDB was used to evaluate the determinants of overall survival (OS) of young adults ≤ 50 years with MM who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 16,792 patients ≤ 50 years old diagnosed and treated for MM from 2004 to 2017. Multivariable cox regression analysis with backward elimination was utilized to identify the independent survival factors, using significance level of p &lt; 0.05. Kaplan-Meier survival curves were generated and SAS version 9.4 was used to analyze the data. Results: Overall median survival time was 119 months; while survival rates of 1, 3, and 5-year were 90.6%, 78.0%, and 67.8%, respectively. Multivariable cox regression analysis with backward elimination method revealed that there were 13 significant independent survival factors: age, sex, race, ethnicity, Charlson-Deyo score, insurance status, facility type, median income, education level, distance to facility, year of diagnosis, hematopoietic stem-cell transplantation (HSCT), and treatment-regimen. Male patients were more likely to die compared to female patients (HR = 1.22, p &lt; 0.0001). Black patients were predicted to have less death events compared to White patients (HR = 0.91, p = 0.004). In addition to that, Hispanic patients were more likely to die compared to non-Hispanics (HR = 1.2, p = 0.0006). Subjects who were treated in non-academic facilities were more likely to die compared to the ones who received care in academic centers (HR = 1.2, p &lt; 0.0001). Moreover, patients with Medicare (HR = 1.65, p &lt; 0.0001), Medicaid (HR = 1.49, p &lt; 0.0001), and no insurance (HR = 1.63, p &lt; 0.0001) had higher chance of death compared to those with private insurance. Patients with lower income &lt; $38,000 were more likely to die compared to income ≥ $63,000 (HR = 1.19, p = 0.0007). Only 6.8% of patients underwent HSCT and 93.2% did not. Patients undergoing HSCT had worse OS compared to those treated without HSCT (HR = 0.36, p &lt; 0.0001). Detailed analysis will be presented. Conclusions: In this large cohort of real-world data analysis of very young MM patients, we found that White and Hispanic patients age ≤ 50 years had significantly inferior survival compared to Black and non-Hispanic patients. Patients with lower income, lower education level, non-private insurance, and those without access to academic centers for MM care had worse survival outcomes. The findings can be useful for designing prospective studies addressing disparity and equitable access to MM care. Despite being a pivotal part of MM therapy, HSCT utilization in the real-world setting is minimal. The barriers to HSCT utilization and the reason why it is inferior to no-HSCT in real-world setting need to be identified and addressed.

High Hospital-related Costs at the End-of-life in Patients With Multiple Myeloma: A Single-center Study.

High Hospital-related Costs at the End-of-life in Patients With Multiple Myeloma: A Single-center Study.

Trends in presentation, treatment, and survival in young multiple myeloma patients age 50 and under from 2000-2021.

e20028 Background: Multiple myeloma (MM) is a disease predominantly of older adults with an average age of 69 at diagnosis. Limited data is available on the diagnostic details and outcomes of MM patients ≤50 years old, and particularly how these trends have changed over the past two decades. We present data from one of the largest retrospective cohorts of younger MM patients. Methods: This retrospective review identified 213 MM patients by pooling two datasets: 88 MM patients aged ≤50 years at first stem cell transplant (SCT) between 1/1/2000-6/1/2021 at University of California (UC), San Diego; and 125 MM patients age ≤50 years old at diagnosis between 1/1/2014-7/1/2021 at UC Davis. Demographics, diagnostic details, treatment, response, and overall survival (OS) data were collected. Results: The pooled dataset included 209 patients with MM and 4 with plasma cell leukemia. The median age was 45, with 58 (27%) Hispanic and 37 (17%) Black patients. In 89 patients with available data, 23% were R-ISS-1, 58% were R-ISS-2, and 19% were R-ISS 3. Overall, 14% of patients had high-risk cytogenetics [ t(4;14), del17p, or t(14;16]] . Patients diagnosed and treated in 2000-2010 were more likely to have received doublet or cytotoxic chemotherapy for induction therapy, while 80% of patients in 2010-2021 received triplet-based therapies. Responses to induction improved across decades, with 23% of patients in the earlier cohort vs 49% patients in the later cohort achieving a very good partial response (VGPR) or better. Eighty-five percent of patients received a SCT, the majority being autologous with only 13 upfront or salvage allogeneic SCTs in the earlier and 1 in the later cohort. The median OS for the entire cohort is 168 months, 171 months in the early cohort, and not reached in 2011-2021 cohort. Conclusions: We present retrospective data of a large and diverse cohort of California MM patients ≤50 years old, with nearly 50% of patients from underrepresented populations spanning over 2 decades. We found similar diagnostic features and risk group to those reported in the general MM population. Noticeable improvements in treatment responses were seen in the later decade with the introduction of modern therapies. A median OS of 14 years for the entire cohort over 20 years offers a glimpse into the hopeful promise for extended survival of younger patients as more effective therapies lead to deeper and more durable responses. [Table: see text]

Survival Trends in Young Patients with Multiple Myeloma: Focus on Racial-Ethnic Minorities

Background: Population-based studies have shown outcome disparities in multiple myeloma (MM) patients by race-ethnicity. A definite improvement in overall survival (OS) as well as a trend towards younger age at diagnosis has been seen in MM over recent years. Hispanics and African-Americans (AA) have younger median age at MM diagnosis and while overall MM patients have had improving OS, a focus on younger patients, especially racial-ethnic minorities has been missing.Methods: The Surveillance Epidemiology and End Results (SEER) 18 Registry data (1973-2014) was utilized for patients with a confirmed diagnosis of MM. Young MM patients were defined as being diagnosed at <40 years of age. Cases that received a diagnosis at death certificate or autopsy, no follow-up records, no documented age at diagnosis were excluded. OS was estimated using the Kaplan-Meier method. Survival curves were compared using log-rank tests. Expected survival was estimated using the age and sex specific death rates from the US population. Relative survival rate (RSR) was provided as the ratio of the observed to expected survival at individual time points. 5-year and 10-year RSR were calculated for patients diagnosed in 1995 or earlier (no novel agents or stem cell transplant; SCT), between 1996-2002 (SCT but no novel agents) and 2003 or later (SCT and novel agents) was calculated.Results: A total of 89,451 MM patients with MM were available in the SEER database, of which 1,460 were diagnosed at ≤40 years of age (young MM) and met study inclusion. These included 59% males and 41% females with a median age at diagnosis 37 years (range 18-40) for the whole group. Median follow up for the whole cohort was 44 months (range: 0-419 months). Mutually exclusive racial subgroups included non-Hispanic Whites (NHW; 46.8%), non-Hispanic Blacks (NHB; 28.2%), Hispanic (18.4%), Asian (5.5%), Native American (<1%) and other (<1%). No significant differences were noted between the racial subgroups for median age at diagnosis, gender distribution or listed cause of death. Survival analyses were done between NHW, NHB and Hispanics, the 3 largest subgroups in the selected cohort. 5-year and 10-year RSR improved for patients age >40 years diagnosed in the 3 time periods for NHW, NHB and Hispanics (all p<.0001) as well as both genders (p<.0001). For the young MM patients there was a significant improvement in RSR noted over time for both genders (p<.0001) and among racial subgroups for NHW (p<.0001) and NHB (p<.0001) but not for Hispanics. Change in 5-year RSR for Hispanic young MM patients for the 3 time periods was 39%, 48% and 56% (p=.08) and for 10-year RSR was 21%, 35% and 33% (p=.13) (Figure 1).Conclusions: There has been a significant improvement in median OS of MM patients over time due to availability of novel therapeutics including access to SCT. Racial disparities exist in outcomes and we show that young Hispanic MM patients have not yet realized a benefit in outcomes over time possibly due to variability in disease biology, response to therapy or access/utilization of the effective novel therapeutics. These factors need to be explored further to improve outcomes in all MM patients and eliminate disparities, especially the youngest subgroup of patients where survival, productivity and well-being carry different implications. [Display omitted] DisclosuresAilawadhi:Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Sher:LAM Therapeutics, Inc: Research Funding.

Race as a predictor of outcome in young patients with myeloma.

e20019 Background: Multiple myeloma (MM) is a malignancy that affects Black Americans (BA) more often and at earlier age than White Americans (WA). BAs still frequently receive suboptimal care and are underrepresented in clinical trials or retrospective analyses. However, recent studies have shown that BA MM patients treated with standard-of-care regimens have similar if not superior outcomes than WA patients. The median age of MM diagnosis is 69 years; but ten percent of individuals develop MM before age of 50 years. Limited data are available regarding the outcomes and characteristics of this younger patient population. Herein, we specifically investigate the outcome of young MM patients. Methods: We retrospectively analyzed young MM patients (age &lt; 50) diagnosed between 1992 and 2016 at The Ohio State University Comprehensive Cancer Center. After informed consent, data pertaining to patient demographics and MM characteristics were collected in a coded database. Descriptive statistics was used to summarize disease characteristics; chi-square or Wilcoxon rank-sum tests were used to compare outcomes between BA and WA patients. Overall Survival (OS) was estimated by Kaplan-Meier method, with log-rank test applied to test the statistical differences between survival curves. Two-sided p-values &lt;0.05 were considered statistically significant. Results: In our institutional database, we identified 264 individuals who developed MM before age of 50 years (median age=46; range: 17-50 years). 211 of them had matched cytogenetic studies and were included in the final analysis. The majority of these patients were male (66%), had IgG disease (47%), and stage II-III at presentation (52%). 196 of patients (93%) underwent at least one autologous stem cell transplant-ASCT, with 23 of them receiving more than one ASCT (15%) and 9 of them undergoing allogeneic stem cell transplant (4%). In all, median OS was 9.84 years (95% CI, 6.75-12.92 years), which is higher than in unselected older MM patients. 24% of the patients (n=51) were BA while the remaining (n=160) were WA. We observed no statistical differences in terms of patient characteristics, disease stage, or cytogenetics between BA or WA, except for a statistically significant prevalence of del(13q) in WA patients (39% vs. 30%; p= 0.012). In our cohort, BA and WA patients received transplant at similar rates (94% vs. 88%, p-value=0.137). Finally, we observed an inferior median OS of 8.59 years (95% CI, 6.40-10.78 years) in WA compared with BA patients (median OS: not reached; p-value= 0.038), with 5-year OS of 86% in BA compared with 65% in WA patients. Conclusions: We report a retrospective cohort of young MM patients. In our cohort, we observed less prevalence of del(13q) and superior OS of BA compared with age-matched WA patients. This suggests that young BA MM patients benefit from standard-of-care approaches and strategies should continue to be pursued to improve access to care and optimize treatments.

Immunomodulators in newly diagnosed multiple myeloma: current and future concepts

ABSTRACT Introduction: Impressive therapeutic progress is being made in the management of multiple myeloma (MM). his progress is related to the introduction of several new classes of therapeutic agents including proteasome inhibitors, immunomodulatory drugs (IMiDs) and monoclonal antibodies (MoAbs). Areas covered: In this manuscript, the role of the IMiDs thalidomide and lenalidomide in the management of newly diagnosed MM is discussed. The mode of action of IMiDs and their role in the management of newly diagnosed MM patients is highlighted. In addition, clinical data on how MoAbs such as the anti-CD38 antibody daratumumab can further increase the efficacy of IMiD-based first-line anti-myeloma regimens are provided. A database search in PubMed was carried out. Expert Opinion: Immunomodulation has become an indispensable part of successful anti-myeloma regimens both at relapse and at diagnosis. The combination of lenalidomide plus dexamethasone with an anti-CD38 MoAb such as daratumumab and a proteasome inhibitor such as bortezomib is currently one of the most potent first-line treatment regimens for MM. A better understanding on how IMiDs synergize with existing and new anti-myeloma treatments can further improve the outcome for patients. Optimal first-line therapy will continue to benefit the long-term outcome of a growing population of young and elderly MM patients.

Impact of Extended Treatment Interval on the Prognosis of Multiple Myeloma Patients: A Retrospective Study

Introduction: Recently, treatment with proteasome inhibitors and immunomodulators has improved the prognosis of multiple myeloma (MM). However, in a complex real-world situation, the patient’s ability to undergo regular and timely treatment as prescribed in clinical trials has not been studied, as well as the impact of extended treatment intervals due to different reasons. This study aimed to evaluate the treatment interval and clinical characteristics of 122 patients with primary myeloma in our hospital and explore the prognostic effects of different treatment intervals. Methods: In total, 122 patients with MM were analyzed retrospectively in our hospital from January 2007 to June 2018. The clinical and laboratory data (such as age, International Staging System [ISS] stage, chromosome, etc.) and subsequent treatment intervals were analyzed. The Cox proportional hazard regression model was used for univariate and multivariate analyses of overall survival (OS) and progression-free survival. The Kaplan-Meier method was used in survival analysis, and the log-rank test was used to test survival difference. p < 0.05 was considered to indicate statistical significance. Results: We found that prolonging the interval treatments (>28 days) shortened the OS in the younger and high-risk subgroups. On the contrary, the OS of the older and low-risk subgroups was not shortened. OS was also shortened in patients who were suitable for transplantation but did not receive a transplant. Univariate and multivariate analyses showed that extension of treatment interval was a risk factor for OS shortening. In addition, prolonged treatment interval was due to iatrogenic and family reasons. Conclusion: Extended treatment interval is unfavorable in young and high-risk MM patients and those suitable for transplantation but who did not receive a transplant. However, it has a faint impact on the elderly and low-risk subgroups.

Breaking the Glass Ceiling of Age in Transplant in Multiple Myeloma

Breaking the Glass Ceiling of Age in Transplant in Multiple Myeloma

Profound MRD negativity rates after frontline tandem autologous-allogeneic stem cell transplantation followed by bortezomib maintenance in high-risk or young myeloma patients

Prior studies suggest that allogeneic (allo) stem cell transplant (SCT) can overcome high-risk (HR) cytogenetics associated with poor outcome in multiple myeloma (MM). Despite being the only potentially curative therapy for MM, the use of allo SCT remains controversial due to unacceptably high nonrelapse mortality (NRM; 10-15%), morbid extensive chronic graft-versus-host disease (cGVHD; 50-80%) and high relapse rates (50-60%). We hypothesized that bortezomib (BTZ) after allo SCT might decrease both relapse and cGVHD in HR disease and young MM patients (pts) who have the greatest loss in years of life from MM.

PF579 TUMOR CIRCULATING PLASMA CELLS DETECTED BY FLOW CYTOMETRIC SINGLE PLATFORM METHOD ARE RELATED TO NEGATIVE PATIENTS‘ CHARACTERISTICS IN MULTIPLE MYELOMA

Background:Multiple myeloma (MM) is a clinically heterogeneous disease and several classification systems have been developed to stratify patients in low, intermediate or high risk. Tumor Circulating Plasma Cells (TCPC) are considered a marker of high‐risk disease in all plasma cell disorders. To date, different methods are available to detect TCPC in peripheral blood, but they are barely reproducible and time consuming.Aims:For the first time the amount of TCPC was quantified in newly diagnosed MM patients with a single platform flow cytometric method and was evaluated their correlation with patients‘ baseline characteristics.Methods:Whole peripheral blood (PB) samples from 413 newly diagnosed young MM patients enrolled in the UNITO‐MM‐01/FORTE trial were included in the study. For the single platform technique, the antibody combination CD38PC7/CD138PC5.5/CD45KO/ CD56PE/CD19PB was mixed with 100 μL of EDTA PB, dispensed with reverse pipetting, and incubated for 15 min at RT, added with 500 μL of lysing solution and, after 15 min, 100 μL of flow count fluorospheres were dispensed with reverse pipetting and cells acquired with Navios flow cytometer. Intracytoplasmic kappa and lambda were tested to confirm the TCPC clonality.Results:Circulating Plasma Cells (CPC) were found in 390 out of 413 samples (94.4%), with median values of 0.03% (range: 0%&gt;51%) and 2.37/mm3 (range: 0/mm3–6272/mm3). White blood cells were 5710/mm3 (range: 1752/mm3–26102/mm3); median CPC events 58 (range: 0–441.000); cellular events acquired were 190.000 (range: 4.428–1.300.000).TCPC were found in 272 samples (66%) with a median value of 1.24/mm3 (range 0.06/mm3 ‐ 6272/mm3).Patients were stratified according to different baseline characteristics and median values of absolute TCPC were compared. The most significant statistical differences (p &lt; 0.001) were: Hb &lt;10 (12.9/mm3) vs ≥10 (0.81/mm3); ISS I (0.30/mm3) vs ISS II (2.85/mm3) vs ISS III (5.14/mm3); R‐ISS I (0.25/mm3) vs II (2.76/mm3) vs III (5.14/mm3); Albumin &lt;3.5 g/dL (2.76/mm3) vs ≥3.5 g/dL (1.05/mm3); β2‐microglobulin &lt;3.5 mg/dL (0.67/mm3) vs 3.5 mg/dL‐5.5 mg/dL (3.88/mm3) vs &gt;5.5 mg/dL (16.47/mm3); LDH ≤upper limit (1.14/mm3) vs &gt;upper limit (7.36/mm3); PC in biopsy &lt;60% (0.60/mm3) vs ≥60% (2.76/mm3); with 1q gain (3.18/mm3) vs without (1.18/mm3); Morgan risk Standard (1.16/mm3) vs High (3.00/mm3) (presence of del17 and/or t(4;14) and/or t(14;16) and/or 1q gain).Moreover, the TCPC were sorted in quartiles according to the absolute values (0/mm3–0/mm3, 0/mm3–1.24/mm3, 1.24/mm3–8.3/mm3, 8.3/mm3–6272/mm3) and a correlation between the increasing levels of TCPC and the parameters mentioned above was observed.The most significant correlations expressed by Cramer's V were observed between TCPC and: hemoglobin (V = 0.41), ≥60% of plasma cells in biopsy (V = 0.28), ISS (V = 0.26), β2‐microglobulin &lt;3.5 mg/dL vs 3.5 mg/dL‐5.5 mg/dL vs &gt;5.5 mg/dL (V = 0.26), R‐ISS (V = 0.24), Morgan risk (V = 0.24 p &lt; 0.001), 1q gain (V = 0.24) all with a p &lt; 0.001.Summary/Conclusion:The single platform flow cytometric method allowed us to quantify TCPC in a high number of MM patients and the values obtained were strongly related to the worst clinical and cytogenetic features. This method is fast, not expensive, feasible with a small amount of PB and can be easily performed in a high number of patients.

Clinical characteristics of young multiple myeloma patients: a single-center analysis of 30 patients

Because multiple myeloma is rare in young people, there are fewer reports on the same. Thus, its clinical aspects and prognosis remain unelucidated. We retrospectively evaluated 30 patients with multiple myeloma aged ≤ 45 years at diagnosis. We divided them into three groups based on their cytogenetic risks: standard risk (SR), high risk (HR), and unknown risk. The frequency of HR patients was 36.6%, the highest of the three groups, unlike the previous report. The median progression-free survival (PFS) was 35 months (SR vs. HR, 46 vs. 29 months), and the median overall survival (OS) was not reached (NR) (SR vs. HR, NR vs. 82 months). The OS was significantly worse, and the PFS also appeared inferior in HR patients. The International Staging System score was not associated with OS. Thus, young patients with myeloma appeared to have a higher frequency of HR features, suggesting that instead of age, the cytogenetic risk was a significant prognostic factor.

Survival Outcomes of Young Multiple Myeloma Patients: A Single Center Experience

Multiple myeloma (MM) is a disease of the elderly. It shows rapidly increasing incidence with increased age. Although MM is rare in young people, patients diagnosed before the age of 50 years account for 10% of the overall incidence and approximately 2% are diagnosed before 40 years of age. The aim of the study was to assess the clinical results of the young MM patients diagnosed at the age of ≤45 years.All the MM patients who were ≤45 years old at the time of diagnosis and who were admitted to our clinic between January 2004 and December 2017 were retrospectively assessed. There was a total of 31 patients and 14 (45.2%) of them were females and 17 (54.8%) of them were males. The mean age was 40.4±3.8 years. The most frequent myeloma types were Ig G Kappa (n:12, 38.7%) and Kappa light chain (n: 10, 32.3%). The remaining types were Ig A lambda (n:4, 12.9%), Ig G lambda (n:2, 6.5%), Lambda light chain (n: 2, 6.5%) and non-secretory myeloma (n:1, 3.2%). Before transplantation 12 patients (38.7%) were in complete remission, 11 patients (35.5%) were in very good partial remission, 4 patients (12.9%) were in partial remission state and 4 patients (12.9%) had refractory disease. VAD + VCD protocol was given to 12 (38.7%) patients. 6 (19.8%) patients had VCD, 3 (9.7%) got VCD + VRD, 2 (6.5%) got VAD and 8 (25.8%) got other chemotherapy protocols. Transplantation was done in 26 patients (83.9%). Overall 9 patients (29%) died during the study period. Second or tandem transplantation was performed to 10 patients and 30% (n:3) of these re-transplanted patients died. The overall survival for these patients was estimated to be 70% (95% CI: 64.2-75.8).In conclusion MM in patients younger than 45 years is rare. In these patients Ig G Kappa and Kappa Light chain types are the most frequent types. Heterogeneous of individual patients may exist within these young myeloma patients. For those who are expected to show a poor response to current treatments despite their young age, the efficacy of an alternative therapeutic strategy such as front line allo-HSTC should be further investigated. DisclosuresNo relevant conflicts of interest to declare.