Elderly Multiple Myeloma Patients Research Articles

ASCT: A Viable First-Line Treatment Option for Elderly Multiple Myeloma Patients Without Access to New Drugs

ASCT: A Viable First-Line Treatment Option for Elderly Multiple Myeloma Patients Without Access to New Drugs

MM-448 ASCT: A Viable First-Line Treatment Option for Elderly Multiple Myeloma Patients Without Access to New Drugs

MM-448 ASCT: A Viable First-Line Treatment Option for Elderly Multiple Myeloma Patients Without Access to New Drugs

Elderly (> 70 years) Multiple Myeloma Patients Benefit Equally from Autologous Hematopoietic Stem Cell Transplantation When Compared to Younger Patients

Autologous Hematopoietic Stem Cell Transplantation (AHSCT) performed after induction therapy is the standard of care for newly diagnosed Multiple Myeloma (MM) patients who qualify. Our institution has performed AHSCT for MM since 1991, and in this study, we sought to retrospectively examine the outcomes of 303 MM patients who underwent AHSCT from 1991-2021. We focused on Overall Survival (OS) and Progression-Free Survival (PFS) in patients in addition to Landmark survival (1-year post-transplantation). We found that in elderly patients > 70 years of age there was no significant difference in OS at 12 years, with 51% for patients < 70 years of age and 50% > 70; these were the same numbers for PFS at 12 years as well. We also found that median overall survival is improving overall with each decade in our transplanted MM patients with patient survival improved to over > 80% regardless of age at 7 years, when the previous median overall survival was 6 - 6.6 years before 2001. Given our findings, supported by others, we show that survival is continually improving over time in MM AHSCT patients and that AHSCT can be performed safely with equivalent landmark and long-term PFS and OS in patients of advanced age.

All-oral triplet iberdomide, ixazomib, and dexamethasone in elderly patients with multiple myeloma at first relapse: Results of the IFM phase 2 study I2D.

7507 Background: The triplet combination daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are to date the standard of care for patients with transplant ineligible (TI) newly diagnosed multiple myeloma (MM). Most TI patients therefore present with MM refractory to lenalidomide and daratumumab at first relapse and represent a difficult-to-treat population. Iberdomide is a novel oral cereblon E3 ligase modulator (CELMoD) that demonstrated promising activity in MM patients refractory to lenalidomide/pomalidomide. Here, we report efficacy and safety results of the oral triplet iberdomide, ixazomib and dexamethasone in elderly patients with MM at first relapse. Methods: The Intergroupe Francophone du Myélome (IFM) prospective, multicenter, phase 2 study I2D enrolled MM patients aged over 70 years at first relapse (NCT04998786).Patients received oral iberdomide (1.6 mg on day 1 to 21), ixazomib (3 mg on day 1,8,15) and dexamethasone (20 mg on day 1,8,15,22 on cycle 1-2 and 10 mg on day 1,8,15,22 on cycle 3-6) (28-day cycle) until disease progression or unacceptable toxicity. The primary endpoint was very good partial response (VGPR) rate. Results: Seventy patients were included from Dec 2021 to May 2023 in 19 IFM centers. Median age was 76. The International Myeloma Working Group (IMWG) frailty score was >2 in 35 (50%) patients. In evaluable patients (54/70), cytogenetic analysis revealed del(17p) in 10 patients (18.5%) and t(4;14) in 8 (15%) patients. Based on inclusion criteria, all patients received 1 prior line of treatment, including lenalidomide in 87% (refractory, 74%) and daratumumab in 40% (refractory, 37%) of patients. Median time from MM diagnosis to study enrolment was 28 months. At data cut-off, 36 (51%) patients discontinued the study due to disease progression (n=30), adverse event (n=4) or death (n=2). After a median follow-up of 12 months, the overall response rate was 64%, including 33% VGPR. The median progression-free survival (PFS) was 13 months and the 12-month overall survival (OS) was 85% (77-95% 95% CI). In patients with MM refractory to both lenalidomide and daratumumab (n=26), the median PFS was 10 months. Overall, the triplet I2D was well tolerated. Most common non-hematologic adverse events (AE) were infection (30% of patients), peripheral neuropathy (20%), diarrhea (19%), and were mostly grade 1 or 2. Most common grade 3-4 treatment related AEs (>5% of patients) were neutropenia (46%), thrombocytopenia (9%) and infection (8%). Four patients discontinued treatment due to a severe AE (cytopenia (n=3), skin rash (n=1). Conclusions: The oral tripletiberdomide, ixazomib and dexamethasone demonstrated a favorable efficacy / safety profile in elderly MM patients at first relapse, including in patients with lenalidomide and daratumumab refractory disease. Clinical trial information: NCT04998786 .

Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma

To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), β2-microglobulin (β2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that β2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

Elderly Patients with Newly Diagnosed Multiple Myeloma: Continuous or Fixed Duration Treatment?

Multiple myeloma (MM) presents unique challenges in the elderly population due to increased frailty and comorbidities. Balancing treatment efficacy, safety, and quality of life is essential in managing elderly patients. While two-drug regimens were often favored for elderly patients, recent studies show promising outcomes with anti-CD38 antibody-based therapies, particularly daratumumab and lenalidomide with minimal dexamethasone. Continuous low-intensity treatments have shown improved progression-free survival and overall survival, with significant benefits observed in elderly patients. The DRd combination has now emerged as the standard of care for elderly MM patients, offering a favorable balance of efficacy, safety, and convenience. Ongoing trials are evaluating the addition of bortezomib in an induction phase for fit patients. New-generation immunotherapies hold promise for further refining treatment approaches, potentially leading to treatment discontinuation in select patient populations with sustained minimal residual disease negativity.

Steroid-free combination of 5-azacytidine and venetoclax for the treatment of multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell malignancy that, despite an unprecedented increase in overall survival, lacks truly risk-adapted or targeted treatments. A proportion of patients with MM depend on BCL-2 for survival, and, recently, the BCL-2 antagonist venetoclax has shown clinical efficacy and safety in t(11;14) and BCL-2 overexpressing MM. However, only a small proportion of MM patients rely on BCL-2 (approx. 20%), and there is a need to broaden the patient population outside of t(11;14) that can be treated with venetoclax. Therefore, we took an unbiased screening approach and screened epigenetic modifiers to enhance venetoclax sensitivity in 2 non-BCL-2 dependent MM cell lines. The demethylase inhibitor 5-azacytidine was one of the lead hits from the screen, and the enhanced cell killing of the combination was confirmed in additional MM cell lines. Using dynamic BH3 profiling and immunoprecipitations, we identified the potential mechanism of synergy is due to increased NOXA expression, through the integrated stress response. Knockdown of PMAIP1 or PKR partially rescues cell death of the venetoclax and 5-azacytidine combination treatment. The addition of a steroid to the combination treatment did not enhance the cell death, and, interestingly, we found enhanced death of the immune cells with steroid addition, suggesting that a steroid-sparing regimen may be more beneficial in MM. Lastly, we show for the first time in primary MM patient samples that 5-azacytidine enhances the response to venetoclax ex vivo across diverse anti-apoptotic dependencies (BCL-2 or MCL-1) and diverse cytogenetic backgrounds. Overall, our data identify 5-azacytidine and venetoclax as an effective treatment combination, which could be a tolerable steroid-sparing regimen, particularly for elderly MM patients.

Daratumumab Treatment for "Truly Frail" Elderly Myeloma Patients.

Remarkable advancements have been made in the treatment outcomes of multiple myeloma (MM) patients; however, for frail elderly patients, these treatment outcomes are still insufficient. Elderly MM patients are increasing, as are their treatment regimens. There is a heightened demand to assess these patients in order to provide optimized treatments. While continuous treatment is more common for MM patients when compared to fixed-duration treatment, due to the risk of treatment interruption causing reduced survival rates, effectiveness and safety are essential. Treatment goals vary for each patient, but must preserve their quality of life (QOL). When planning treatments for these patients, frailty evaluation is increasingly emphasized as a stratification factor which helps develop accurate screening tools. Daratumumab (DARA) therapy, used globally, is not only effective in frail elderly MM patients, but also has QOL benefits. Proficiency in utilizing DARA regimens is potentially advantageous for patients not included in clinical trials, and innovative usage can further broaden its scope. The development of tools to accurately assess frailty and the establishment of optimal treatments for frail elderly MM patients are imperative. This review is an overview, challenging the frailty assessments for MM patients, re-examining the evidence for DARA regimens in frail elderly MM patients, and discussing potential areas for improvement.

Autologous stem cell transplantation in patients older than 65 years with multiple myeloma: a real-world study

The treatment of elderly multiple myeloma (MM) patients with autologous stem cell transplantation (ASCT) is a controversial procedure. Most clinical trials evaluating the safety and efficacy of ASCT have primarily included patients younger than 65 years. This was a retrospective analysis of patients with MM who underwent ASCT between 2008 and 2018. Patients at or over 65 years were compared with patients under 65 years. We analyzed treatment-related mortality (TRM), response rate, progression-free survival (PFS) and overall survival (OS). Two hundred and twenty-one patients were included: 50 patients at or over 65 years, (median age 68 years), including 7 patients over 70 years and 151 patients under 65 years, (median age 57 years). No differences were found in the neutrophil and platelet engraftment, median days of hospitalization and life support requirement during the hospitalization period for the ASCT. No statistically significant differences were found in the incidence of TRM between both groups at 100 days post-transplant (2% vs. 2.9%, p=0.322). The ASCT improved complete response and stringent complete response rates (44% vs. 37%, p < 0.001). Survival was not modified by age: after a median follow-up of 53 months, the estimated PFS rates at three years were 63% and 60% (p=0.88) and the OS rates at five years were 75% and 74% (p=0.72), respectively. Our data suggest that the ASCT is feasible in selected elderly patients with MM over 65 years of age, achieving response and survival rates similar to those of younger patients.

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

e20035 Background: The survival of older adults with multiple myeloma (MM) continues to improve due to advancements in therapy but there is limited real-world data around the outcome of elderly (≥ 75 years old) MM patients. These patients are at risk due to comorbidities, frailty and potential for reduced tolerance to treatment. In this IRB approved retrospective analysis, the NCDB was used to evaluate the 30-day mortality and the determinants of overall survival (OS) of elderly MM patients who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 54,766 patients ≥ 75 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 produced, and SAS version 9.4 was used to analyze the data. Results: Overall median survival time was 23 months; while survival rates of 1, 3, and 5-year were 61.9%, 38.0%, and 23.6%, respectively. Multivariable cox regression analysis with backward elimination method revealed that there were 10 significant independent survival factors including age, sex, race, ethnicity, education level, Charlson-Deyo score, facility type, median income, year of diagnosis, and treatment-regimen. Male patients were more likely to die compared to female patients (HR = 1.08, p &lt; 0.0001). Black patients were predicted to have less death events compared to White patients (HR = 0.90, p &lt; 0.0001). In addition to that, patients of Hispanic ethnicity were more likely to die compared to non-Hispanic patients (HR = 1.16, p &lt; 0.0001). Subjects who were treated in non-academic facilities were more likely to suffer death compared to the ones who received care in academic centers (HR = 1.15, p &lt; 0.0001). Patients with median income &lt; $38,000 (HR = 1.10, p &lt; 0.0001), $38,000-$47,999 (HR = 1.06, p = 0.0011) and $48,000-$62,999 (HR = 1.04, p = 0.0031) were more likely to die compared to patients with higher median income ≥ $63,000. The hematopoietic stem cell transplantation utilization rate was 0.1%. The 30-day mortality rate was 8%. Detailed analysis will be presented. Conclusions: This large real-world analysis of elderly MM patients shows that White and Hispanic patients have inferior OS compared to Blacks and non-Hispanics. Patients with lower economic status and those treated at a non-academic facility also had inferior survival compared to those with higher income and with access to care at an academic facility. The 30-day mortality is strikingly high (8%) in the elderly. The unacceptably high mortality could be improved by facilitating access to high quality care and prompt use of novel agents. Prospective studies are needed to identify and address determinants of disparity in MM care in elderly patients.

Early Onset of Smoldering Disease Correlates with Rapid Progression to Symptomatic Multiple Myeloma

Multiple Myeloma (MM) remains an incurable cancer of terminally-differentiated plasma cells that is universally preceded by the premalignant precursor Monoclonal Gammopathy of Undetermined Significant (MGUS) and later with Smoldering MM (SMM) characterized by greater plasma cell clone volume. The time between the malignant transformation of plasma cell clone to the symptomatic MM, i.e., Latency Period (LP), remains largely unknown for the majority of MM patients. The LP can be affected by age such that MM in younger age patients had a shorter LP than MM diagnosed at an older age. Here, we sought to determine whether the later stage of LP i.e., from SM diagnosis to symptomatic MM. We hypothesize that patients with SM diagnosed at the younger age had faster rate of progression to symptomatic MM. Methods: The National Cancer Database (NCDB) covers >70% of all cancer patients in the U.S. Since, SMM and MM share the same ICD code, we defined SMM who did not receive any treatment within 3 months following a diagnosis of MM similar to the methods used by others (Ravindran et al. Blood Cancer J. 2016). Initiation of systemic treatment was considered as a surrogate of progression to symptomatic MM. Overall survival (OS) for SM patients was calculated from initiation of systemic treatment after they progressed to MM, estimated by the Kaplan-Meier method, and compared with the log-rank test. Cumulative incidence of progression from SM to MM was calculated with death as a competing risk and compared with the Gray's test. Multivariable Cox and logistic regression analysis were performed to identify independent predictors of OS and progression to MM, respectively. Results: 68,234 patients that had been diagnosed with MM/SMM ICD code were reviewed and, of those, 12,984 patients with SMM were then identified. Among the SMM patients, 3002 (23%) were black, 6796 (52%) were male, and median age at diagnosis was 69 years (range: 22 - 90). SMM patients’ insurance types were private for 4164 (32%), Medicare for 7420 (57%), Medicaid for 669 (5%), and 260 (2%) were uninsured. The majority of the cases were reported from non-academic hospitals (59%). Patient and treatment characteristics are summarized (Table 1). SMM was diagnosed in black patients a median of 4 years younger than in white patients (median age 66 vs 70 years, p<0.0001). Charlson comorbidity index was >2 for 325 (11%) black and 629 (7%) white patients (p<0.0001). Median annual household income of white patients was higher than black patients (p<0.0001). Median time to progression from SMM to MM was 4.5 months (range: 3 - 64). Progression to MM was observed in 3144 (24%) patients during median follow-up of 39 months. All SMM patients received chemo- or immunotherapy after progression and 867 (7%) underwent hematopoietic cell transplant. The four-year cumulative incidence of progression from SMM to MM patients at ages of <60 vs 60-70 and >70 years was 34% (95% CI: 32 - 35) vs 28% (95% CI: 26 - 29, p<0.0001) and 18% (95% CI: 17 - 19, p<0.0001), respectively (Fig. 1). Four-year cumulative incidence of progression to MM for patients of black and white race was 24.5% (95% CI: 23 - 26) and 24.4% (95% CI: 24 - 25), respectively (p=0.99). Four-year cumulative incidence of progression to MM for patients who were diagnosed between 2010-2012 and 2013-2014 was 25% (95% CI: 24 - 26) and 24% (95% CI: 23 - 25), respectively (p=0.17). On multivariable analysis, each 10-year decrease in age (OR 1.06, 95% CI: 1.05 - 1.06, p<0.0001), white vs black race (OR 1.02, 95% CI: 1.00 - 1.04, p=0.027), and each 1-year decrease in diagnosis year (OR 1.01, 95% CI: 1.00 - 1.01, p=0.015) were associated with progression to MM, however male vs female gender (OR 1.01, 95% CI: 0.99 - 1.02, p=0.26) was not statistically significant. Conclusions: Taken together, our result indicate the rate of SM to MM progression is independently and inversely associated with age of SMM detection. These findings highlight the potentially longer LP in older patients which can denote more indolent disease in elderly MM patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retrospective Analysis of Prognostic Factors and Survival in Multiple Myeloma Patients Aged 65 Years or Older at Diagnosis in a Real-Life Setting and a Proposed New Staging System

Introduction: The incidence of multiple myeloma (MM) increases with age. Novel agents provide better treatment results. However, adults >65 years of age are often underrepresented in clinical trials making it difficult to assess treatment outcomes in older patients. Appropriate strategies are necessary and treatment must be individualized in this heterogeneous population. Methods: We retrospectively reviewed the charts of 534 patients diagnosed with MM between January 2010 and January 2020 who presented to our department. One hundred twenty-three of them were aged 65 years or older at diagnosis and were included in the study. Clinical and laboratory data were collected and potential prognostic factors of overall survival (OS) were evaluated by univariate and multivariate analyses. Results: Of 123 patients analyzed 54.5% (67) were male and 45.5% (56) were female. The median age was 71 years and 32.5% of patients were equal or older than 75 years. Median follow-up time was 28 months (1-117). Median OS and progression free survival (PFS) were 46 and 17 months, respectively. Of the patients 63.4% (78) died during the study period. The patients were divided into 3 groups according to age: 65-69 (47 patients, median OS 68 months), 70-74 (36 patients, median OS 45 months) and ≥75 (40 patients, median OS 36 months) years old (p: 0.022). International Staging System (ISS) stage could be defined in 117 patients (19 had ISS I, 40 ISS II and 58 had ISS III disease). Revised ISS (R-ISS) could also be defined in 117 patients (17 R-ISS I, 82 R-ISS II and 18 R-ISS III). Both ISS and R-ISS could not identify statistically significant differences regarding OS and PFS. Chromosomal abnormalities were detected by fluorescence in situ hybridization (FISH) and conventional cytogenetics in 56 and 39 patients respectively. Eleven of 56 patients and 4 of 39 patients had unfavorable genetic features and due to the small number these patients are not included in the survival analyses. Bortezomib based doublet and triplet induction regimens were given in 86% of patients. Univariate analysis revealed that age, hemoglobin, creatinine, calcium, albumin, extramedullary disease and bone marrow plasma cell (BMPC) percentage were strongly associated with OS. Receiver operating curve (ROC) analysis determined the optimal cut-off value of BMPC 26.5%. On multivariate analysis albumin, extramedullary disease and BMPC ratio retained prognostic value. Presence of none, one, two or all three of these factors could identify 4 patient subgroups showing median OS rates of 108, 55, 25 and 12 months, respectively (p: <0.001) (Figure). Conclusions: MM primarily affects older adults. Hence, there is a need for simple and reliable staging systems for elderly MM patients. We propose a prognostic scoring method for outcome incorporating easy to use variables such as albumin, extramedullary disease and BMPC ratio. Hypoalbuminemia (≤ 3.5 g/dl), presence of extramedullary disease and BMPC ratio ≥ 26.5% predicted different OS ratios in the study population. A validation of the score in an independent series of patients is planned. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Strategies to Optimize the Utilization of Stored Autologous Peripheral Blood Stem Cells for Second Transplantation in Multiple Myeloma

Introduction: Autologous stem cell transplantation (ASCT) is the standard of care and a mainstay in the management of eligible patients with multiple myeloma (MM) and remains relevant in the era of novel therapeutics. ASCT requires stem cell mobilization to collect ample stem cells to provide hematological recovery after myeloablative conditioning. Second ASCT (ASCT2) as salvage therapy in relapsed/refractory MM (RRMM) is a treatment option for patients who achieved disease control for 2 to 3 years after first ASCT (ASCT1). The reported difficulties in mobilizing and collecting additional stem cells following myeloablative ASCT1 have led to the currently adopted practice to collect and store adequate peripheral blood stem cells (PBSCs) for two transplants before ASCT. The preferred PBSC cell dose is 2 to 5 × 106 CD34+ cells per kilogram of recipient weight (CD34+ cells/kg) per transplant; however, with the influx of effective novel agents available for RRMM, the use of ASCT2 is declining. A retrospective cost utilization study showed that at a median follow-up of 3.5 years, only 3% of the cohort received ASCT2. The additional cost of collecting and storing these products is an average of 16,590 USD/patient. Given the limited use of salvage ASCT2, current practice of collecting PBSCs for two transplants should be re-evaluated and carefully selected case-by-case. We investigated potential strategies to reduce the financial burden of PBSC collection, processing, and storage by identifying a subgroup of patients who are less likely to receive an ASCT2, herein avoiding storing extra cells. Materials and Methods: With Institutional Review Board approval, we performed a retrospective descriptive analysis of all MM patients who underwent frontline ASCT from 1/1/2012 to 6/23/2022. We excluded patients who had planned tandem transplants and those who underwent a single ASCT and had all cells infused with no remaining stored cells. We classified all patients who collected a sufficient cell dose for ASCT1 and ASCT2 into two cohorts according to the number of ASCT received; those who received ASCT1 and those who received ASCT1 and ASCT2. Results: We report the descriptive statistics of eligible MM patients from a single stem cell transplant center. Over a median follow-up of 2.0 years, we report findings of 240 patients who collected sufficient PBSCs for ASCT1 and ASCT2. Patients’ median age at PBSC collection was 61 (range 32-77). We classified our cohort by gender, age, race, and average number of days for PBSC collection. We aim to collect a cell dose of 10 x 106 CD34+ cells/kg. Our cohort included more males than females (132/108) and a higher prevalence of African Americans (59%) than Caucasians. Our study showed that only 7% of patients underwent ASCT2 (17/240) with average time between ASCT1 and ASCT2 of 2.9 years. We noticed that 88% (15/17) of patients who received ASCT1 and ASCT2 were ≤ 61 years old at the time of ASCT1 and two patients (12%) were ≥ 70 years. Additionally, a higher proportion of patients utilizing ASCT2 in the youngest age groups is noticeable. Six of 30 patients under 50 years and three of seven patients under 40 years of age (20% and 43%, respectively) underwent ASCT2. The data highlights that utilization of ASCT2 is less common in the elderly population; hence considering PBSC collection for one transplant among the elderly would be a cost-effective strategy. Most stem cell transplant centers inherited a strategy to collect PBSC 10 x 106 CD34+ cells/kg. We noticed that 102 patients required >1 day of PBSC collection to meet the collection goal. Of these patients, 35% were age 65 or older. If we were to change practice and consider PBSC collection for one transplant among the elderly, we could have reduced the number of collection days by 25 and reduced the associated costs of collection, processing, storage, and staffing, as well as space requirements for storage. Conclusion: The utilization of ASCT2 in MM patients is decreasing with the influx of novel therapeutics. Potential strategies are needed to change the practice and reduce the additional financial burden of excess stem cell collection and storage. We suggest that elderly MM patients be considered for PBSC collections for a single transplant. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improved survival in myeloma patients-a nationwide registry study of 4,647 patients ≥75 years treated in Denmark and Sweden.

The prevalence of multiple myeloma (MM) is increasing in Nordic countries and the rest of the western world. Patients aged ≥75 years at diagnosis constitute an increasing proportion of all MM patients, but are underrepresented in randomized clinical trials. There is an urgent need for studies of the characteristics, treatment and outcome in this cohort. We present data from two nationwide population-based registries of all MM patients diagnosed in Denmark from January 1, 2005 until February 18, 2020, and in Sweden from January 1, 2008 until December 31, 2019, including treatment data for patients diagnosed until 2018 (Denmark) and 2019 (Sweden). In total 4,647 patients were ≥75 years at diagnosis, compared to 7,378 younger patients. Patients ≥75 years, accounting for approximately 40% of all MM patients, are a distinct cohort with more advanced disease at diagnosis, reflected by higher International Staging System (ISS) stage, and a higher proportion have renal failure and anemia. We found a more gradual introduction of modern medications in the older cohort than in the younger, despite simultaneous changes in guidelines. Compared to the cohorts in randomized controlled trials that guide the treatment of non-transplant eligible patients, we found a higher proportion of patients ≥75 years and presenting with ISS III in the real-world populations. Nevertheless, response rates and survival are increasing, indicating that modern treatment regimens are effective and well tolerated also in elderly MM patients in real-world populations.

Machine Learning-Based Overall Survival Prediction of Elderly Patients With Multiple Myeloma From Multicentre Real-Life Data.

ObjectiveTo use machine learning methods to explore overall survival (OS)-related prognostic factors in elderly multiple myeloma (MM) patients.MethodsData were cleaned and imputed using simple imputation methods. Two data resampling methods were implemented to facilitate model building and cross validation. Four algorithms including the cox proportional hazards model (CPH); DeepSurv; DeepHit; and the random survival forest (RSF) were applied to incorporate 30 parameters, such as baseline data, genetic abnormalities and treatment options, to construct a prognostic model for OS prediction in 338 elderly MM patients (>65 years old) from four hospitals in Beijing. The C-index and the integrated Brier score (IBwere used to evaluate model performances.ResultsThe 30 variables incorporated in the models comprised MM baseline data, induction treatment data and maintenance therapy data. The variable importance test showed that the OS predictions were largely affected by the maintenance schema variable. Visualizing the survival curves by maintenance schema, we realized that the immunomodulator group had the best survival rate. C-indexes of 0.769, 0.780, 0.785, 0.798 and IBS score of 0.142, 0.112, 0.108, 0.099 were obtained from the CPH model, DeepSurv, DeepHit, and the RSF model respectively. The RSF model yield best scores from the fivefold cross-validation, and the results showed that different data resampling methods did affect our model results.ConclusionWe established an OS model for elderly MM patients without genomic data based on 30 characteristics and treatment data by machine learning.

P956: EMMY COHORT: MANAGEMENT OF NEWLY DIAGNOSED OR RELAPSED/ REFRACTORY MULTIPLE MYELOMA IN PATIENTS AGED OF 80 YEARS AND OVER

Background: Multiple myeloma (MM) patients aged 80 years and older are a population more prone to comorbidities, frailty, cognitive impairment or physical decline and require appropriate management of their myeloma. They are often underrepresented in pivotal clinical trials, with little data available on their management. The EMMY study is a large-scale epidemiological study to assess the epidemiology and real-life management of MM and can focus on the use and real-life efficacy of treatments for newly diagnosed or relapsed/ refractory elderly MM patients. Aims: To describe the management of MM in newly diagnosed or relapsed patients aged 80 years and over and to assess the real-life effectiveness of the treatments received. Methods: EMMY is a descriptive, multicenter, national, non-interventional study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) centers in France. Any patient initiating treatment for MM over a 3-month observation period, from October to December, is included, since 2017. It is a dynamic cohort with the inclusion of approximately 900 patients each year: 2765 patients included at the end of 2019 of which 561 were aged 80 and over (20.3%). Data are updated annually from hospital records up to 2020 at the time of the analysis. Four cohorts of patients aged 80 years and older were analysed according to the line of treatment initiated during their follow-up: L1, L2, L3 or L4+. Median time to next treatment (mTNT), median progression-free survival (mPFS) and median overall survival (mOS) were assessed in months(m). Results: Patients ≥80 years initiated 19.8% of L1s (237/1199) 22.7% (232/1022) of L2s, 22.2% (167/751) of L3s and 18.7% (288/1540) of L4+. They are 7.5% patients ≥85 years old to initiate L1, 8.7% L2, 7.4% L3 and 5.1% L4+. When the line is started, an ECOG ≥2 is reported for 39.4% of L1, 27.7% of L2, 35.1% of L3 and 38.5% of L4 patients and comorbidities recorded in 45.1% of L1, 39.6% of L2, 35.4% of L3 and 38.6% of L4+. In L1, the ISS is level I, II, III for 20.2%, 27.4% and 52.4% of patients. In L1, over the 2017-2020 study period, patients received treatment with PI (58.6%), IMID (32.1%), PI/IMID (4.2%), anti-CD38 (1.3%) or other molecules (3.8%). In L2, they received PI (22.8%), IMID (48.7%), PI/IMID (11.7%), anti-CD38 (14.2%) or other (2.6%), in L3 PI (12.6%), IMID (38, 9%), PI/IMID (9.6%), anti-CD38 (29.3%) or other (9.6%) and in L4+ a PI (23.3%), IMID (20.1%), PI/IMID (5.6%), anti-CD38 (29.2%) or other (21.9%). More than half received a double combination in L1 (50.2%), L2 (59.9%), L3 (54.4%) and L4+ (53.8%). Regarding efficacy, mTNT is 20.3m [15.2; 24.6] in L1, 14.7m [12.3; 20.4] in L2, 10.8m [9; 13.5] in L3 and 8.2m [6.5; 11.2] in L4+. The mPFS is 19.3m [15.1; 23.2] in L1, 12.6m [10.1; 17.5] in L2, 8.9m [10.1; 17.5] in L3 and 5.9m [4.5;7.4] in L4+. The mOS is not reached in L1 (rate at 30m: 76.7% [70; 83.3]) and L2 (rate at 30m: 58.1% [48.1; 68]; it is 25.7m [17.1; NE] in L3 and 18.3m [13.4; 22.4] in L4+. Summary/Conclusion: Patients ≥80 years of age account for more than 20% of de novo and relapsed myeloma patients treated in EMMY. Double combinations are used in half of the situations. Over the study period, PI-based treatments were preferred in L1, IMID-based in L2 and antiCD38 for 30% of patients in L3 and L4+. The benefits in terms of survival are real and this specific population is likely to increase significantly in the near future, requiring human and logistical resources.

Efficacy and safety of autologous hematopoietic stem cell transplantation in elderly multiple myeloma patients: a single center retrospective study

目的评估65岁以上老年多发性骨髓瘤（MM）患者接受自体造血干细胞移植的疗效和安全性。方法回顾性分析自2006年6月1日至2020年7月31日在中山大学附属第一医院诊断并接受含新药诱导方案序贯自体造血干细胞移植的22例65岁以上MM患者的疗效和安全性。接受移植的老年患者均在移植前对重要脏器功能进行评估，自2016年起同时采用国际骨髓瘤工作组虚弱评分评估移植适应证。结果22例患者接受移植时的中位年龄为66.75（IQR 4.50）岁。共20例患者接受了造血干细胞动员，中位采集造血干细胞单个核细胞数为4.53×108/kg，CD34+细胞数为3.37×106/kg，中位采集次数2次。造血干细胞回输后中性粒细胞植入中位时间11 d，血小板植入中位时间13 d，移植后100 d治疗相关死亡率为0。中位随访48.7个月，中位无进展生存时间未达到，中位总生存时间为111.8个月。结论对于经过筛选的≥65岁老年MM患者，自体造血干细胞移植是安全有效的治疗方案。

Evaluation of the Efficacy and Safety of Chemotherapy in Elderly Patients with Multiple Myeloma under Different Frailty Scores

To compare the efficacy and safety of different chemotherapy regimens in elderly multiple myeloma (MM) patients with different Frailty scores. The clinical data of elderly patients with MM were retrospectively analyzed, including age, treatment regimen, efficacy, adverse reactions, and the Frailty score included in the activity of daily living score, the instrumental activity of daily living scale and the Charlson comorbidity index. The patients were divided into fit group, mediate fit group and frail group according to the scoring standard. The treatment efficiency and adverse reaction rates of elderly MM with different physical conditions treated by different chemotherapy regimens were analyzed. Among the 70 patients, the effective rates of the patients in fit group, the mediate fit group, and the frail group were 79.5%, 81%, and 40%, and the effective rates of the fit patients in double and triple groups were 54.5% and 89.3%, 70% and 90.9% for mediate fit patients, 42.9% and 33.3% for frail patients, the triple regimen in fit patients showed obvious advantages, and the difference showed statistically significant (P<0.05), while the efficacy for mediate patients and frail patients showed no significant difference. During the induction of bortezomib, the incidence of adverse reactions for the patients in the triple group (78.6%) was higher than 67.9% in the double group, and the difference showed no statistically significant (P>0.05).There was no significant difference in the 1-year overall survival rate of the patients and with molecular genetic abnormalities among each groups. The therapeutic effect is related to the patient's physical condition. For patients with healthy physique, the triple regimen should be used first. For patients with weak physical constitution, the chemotherapy regimen with low drug toxicity should be selected for safety.

P-162: Compass: a prospective study comparing clinical evaluation with different geriatric screening methods in newly diagnosed elderly multiple myeloma patients

P-162: Compass: a prospective study comparing clinical evaluation with different geriatric screening methods in newly diagnosed elderly multiple myeloma patients

P-160: Efficacy and safety of induction therapy with IAd versus IRd regimen in fragile elderly patients with newly diagnosed multiple myeloma: results of a prospective multicenter clinical trail

<h3>Background</h3> Fragile elderly patients with multiple myeloma (MM) have low survival rate due to complications, poor tolerance and complianceand lack of effective treatment. This prospective multicenter non-randomized controlled study designed to assessment the efficacy and safety of IAd versus IRd in fragile elderly NDMM. <h3>Methods</h3> This ongoing trial is conducted at 14 hospitals. Inclusion criteria was aged ≥ 65 years, IMWG GA score ≥ 2 or Mayo geriatric vulnerability scoring system defined as vulnerable. Patients with acute cardiovascular and cerebrovascular events were excluded. Schemes included IAd (ixazomib 4mg d1,8,15, liposome doxorubicin 40mg d1,dex 20mg d1,8,15,22), IRd (ixazomib 4mg d1,8,15, lenalidomide 25mg d1-14, dex 20mg d1,8,15,22), in 4-week cycles. For patients with effective response (≥ PR) after 6 to 8 cycles, Id maintenance initiated until progression. The study was powered for a primary endpoint of ORR,with PFS,OS,toxicity,health-related Qol as secondary endpoints. This study planned to enroll 120 patients, 60 in each group (chiCTR1900024917). <h3>Results</h3> From Oct 2019 to May 2021, 95 patients were enrolled, median age 71(65-88) yrs, 29.5% of patients ≥75 yrs,18.9% of patients with renal insufficiency(eGFR < 30ml/min, n=13).Efficacy was evaluated in 89 patients,6 were not evaluated, of them,1 had not completed first cycle,2 had dropped out after first cycle,and 3 died in the first course. All patients with renal insufficiency (except for one case), paraplegia, or bedridden were enrolled in IAd group. At a median follow-up of 10 mons (1-20), total ORR was 80.9%, with 80.9% (38/47) in IAd and 81.0% (34/42) in IRd. Median PFS was 16 mons in IAd and was not achieved in IRd. Median OS was not achieved in both two groups,with 12 mon-OS at 81.0%. Cytogenetic high-risk was defined by t(4;14),t(14;16),t(14;20),del(17p) or 1q21 amplification.64.2% of patients stratified as high-risk, 21.0% of patients had ≥ 2 high-risk cytogenetic, median OS was 14 mons, while the median OS of patients with 1 or none high-risk genetic was not achieved (p=0.05).9.5% patients developed hematological grade 3 or above,13.7% patients developed gastrointestinal AE above grade 3 (IAd, n=10; IRd, n=3),13.7% patients with pneumonia(IAd, n=9; IRd,n=4). IRd regimen saw more serious neurotoxicity,5 patients had delirium, mental disorder or cerebral infarction. Fragile elderly patients are relatively vulnerable to death.16 patients died, included 7 deaths due to progression, 4 early deaths (≤60 days),4 treatment abandonment, and 1 unexplained sudden death. <h3>Conclusion</h3> Overall efficacy and safety results support the use of IAD or IRD as frontline therapy for fragile elderly MM patients. Both regimenswere effective, with an overall response rate of 80.9% and 12-month OS of 81.0%. AE were tolerable. Mortality rate are comparably high in fragile elderly MM patients,it is still a challenge for treatment.