Revised Myeloma Comorbidity Index Research Articles

Hematological Malignancies in Older Patients: Focus on the Potential Role of a Geriatric Assessment Management.

Geriatric assessment management is a multidimensional tool used to evaluate prognosis for clinical outcomes and targets for interventions in older adults with cancer receiving chemotherapy. In this review, we evaluated the possible application of geriatric assessment management (GAM) in hematological malignancies. In older patients with Diffuse Large B Cell Lymphoma, GAM might be helpful in both predicting planned hospital admissions and improving quality of life. In chronic myeloid leukemia, the Charlson Comorbidity Index demonstrates how comorbidities could affect treatment compliance and overall outcomes. In multiple myeloma, the application of different scores such as the International Myeloma Working Group Frailty Index and the Revised Myeloma Comorbidity Index can identify frail patients who need suitable interventions in treatment plan (reducing drug dose or changing treatment). Therefore, including GAM in the management plan of older patients with hematological malignancies may direct and optimize cancer care.

Comorbidity indices for prognostic evaluation in multiple myeloma: a comprehensive evaluation of the Revised Myeloma Comorbidity Index and other comorbidity indices with pro- and retrospective applications.

Not available.

Selected Frailty Testing Can Predict for Risk of Febrile Neutropenia in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant

Introduction: Validated myeloma-specific frailty assessment tools, such as the IMWG geriatric assessment tool (IMW GAT) and the revised myeloma co-morbidity index (R-MCI), can be useful to tailor treatment intensity in MM patients (pts). To date, most MM studies of frailty have focused on older, transplant-ineligible populations, with less known about the utility of frailty assessments to guide therapeutic decision-making in younger, transplant pts. We previously reported that frailty scores largely validated in older MM cohorts correlate well with each other, but generally lack ability to discriminate between unfit and fit patients, when applied to a younger transplant population (Devasia et al ASH 2022). Here, we evaluate the use of pre-transplant frailty assessment, using a battery of subjective and objective tools, for predicting common post-transplant toxicities, such as febrile neutropenia (FN) and organ complications. Methods: 162 consecutive MM pts preparing for ASCT and consented for an ongoing prospective frailty study were included. Prior to ASCT, patients underwent comprehensive frailty assessments including: 1) objective measures of fitness [hand grip strength, 6-min walk test (6MWT), Timed Up and Go (TUG), 2) subjective measures of function (Fried Frailty Phenotype (FFP), Rockwood Frailty, KPS, ECOG, HSCT-CI, ESAS), 3) scoring systems integrating both objective and subjective measures (R-MCI, IMWG geriatric assessment tool (IMWG-GAT), and 4) routine screening for organ function (CrCl, serum albumin, hemoglobin, BNP, PFT, and cardiac imaging). Following ASCT, acute grade 3-4 organ-specific toxicities (including FN) occurring from stem cell infusion through engraftment to discharge were prospectively collected (NCI-CTCAE criteria V5.0). Patient/disease characteristics, stem cell dose, engraftment, and transfusion requirements were also collected from electronic patient records. Chi-square and/or Fisher's exact test, as appropriate, were used to assess the association of categorical covariates with frailty scores/measures. Logistic regression was used to assess the association of potential predictors to binary outcomes. All p-values were 2-sided and p<0.05 was considered statistically significant. Results: In total, 162 pts were included in this analysis, median age 62 yrs (range 35-73). Most pts received melphalan 200 mg/m2 conditioning, with 10 pts (6%) dose-reduced to 140mg/m2. All patients received antibiotic prophylaxis. Median stem cell dose was 2.82 x 10 6 CD34+ cells/kg Median neutrophil and platelet engraftment times were 13(10-17) and 14(8-45) days, respectively. 104(64%) pts developed FN post-transplant. Other grade 3-4 toxicities included: GI (41 pts; 25.3%), cardiac (12 pts; 7.4%), lung (4 pts; 2.4%). When correlating with pre-transplant frailty assessments, ECOG performance status and R-MCI appeared to predict for risk of FN, but not for specific organ toxicity (GI, cardiac) nor presence of >1 grade 3-4 toxicity (Table 1). In pts with ECOG 1-2 at baseline, the incidence of FN was 70.9% (83/117) compared to ECOG 0 pts 46.7% (21/45)(p=0.0039). There were no patients with ECOG 3-4 on study. Similarly, 58% (59/101) with baseline low risk frailty as per R-MCI developed FN, compared to 73.8% (45/61) in either R-MCI intermediate or high risk groups (p=0.050). We then evaluated the combined effect of ECOG and R-MCI on prediction of FN. Patients with ECOG 0 plus R-MCI low risk were grouped as “Low risk FN”, patients with ECOG 1-2 plus R-MCI intermediate/high risk were grouped as “High risk FN”. All other patients were grouped as “Intermediate risk FN” (Table 2). By using 2 scores, we could better predict for FN, with 72.5% in “High risk FN” compared with only 37% in “Low risk FN” (p=0.0008)]. Conclusions: This preliminary analysis of an ongoing frailty study in MM patients undergoing ASCT suggests potential utility of combining ECOG and R-MCI in predicting for development of FN. In pts with both ECOG 0 and R-MCI low risk (21% of total cohort), FN occurred in only 37%. Although further validation in a larger cohort is required, this finding may help to select at-risk patients for prophylactic peri-transplant antibiotics whilst avoiding routine use in all patients. This has clinical significance, given the emerging recognition of potentially detrimental effect on the gut microbiota and risk of antibiotic resistance in this setting.

Cumulative Deficits Frailty Index and Relationship Status Predict Survival in Patients with Multiple Myeloma

Background: Frailty is a state of decreased reserve affecting multiple organ systems, thereby increasing vulnerability to stressors. Several tools have been proposed to measure frailty in multiple myeloma (MM), such as the IMWG frailty index, and the Revised Myeloma Comorbidity Index. However, these are based on clinical trial datasets, and include chronological age as one of the indicators of frailty. A frailty index based on the principle of accumulation of health deficits (Rockwood doi:10.1093/gerona/62.7.738), provides a measure of physiologic age. This index can be readily calculated using various combinations of health deficits and has been shown to predict outcomes in several populations. Social support has been associated with improved outcomes in various populations, however its impact on survival in patients with MM has not been well studied. The objective of this study was to assess the impact of frailty measured by a deficit accumulation frailty index and the impact of relationship status on outcomes in patients with newly diagnosed MM. Methods: This is a retrospective study including patients diagnosed with MM between January 6 th, 2005, and September 19 th, 2018. We calculated a deficit accumulation frailty index using previously published methods (McNallan et. al doi.org/10.1016/j.ahj.2013.07.008, Searle et al. doi.org/10.1186/1471-2318-8-24). We used the electronic medical record system at Mayo Clinic in Rochester, MN, to extract data on activities of daily living (14 items) provided by patient-completed questionnaires, and data on comorbidities as recorded by treating providers (16 items), within 6 months prior to diagnosis. Each item was scored as 0, 0.5, or 1, with 1 indicating the presence of deficit (Table 1). The frailty index was defined as the sum of individual scores divided that by the total number of non-missing items. Patients who had N >2 missing items were excluded. Patients with a frailty index ≥0.15 were considered frail. We also extracted data on self-reported relationship status within 6 months prior to diagnosis. Variables were compared between groups using Fisher's exact test and Wilcoxon signed-rank test for categorical and continuous variables, respectively. Univariate and multivariate analysis were performed using Cox proportional hazard models. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between groups using the Log-rank test. P values <0.05 were considered statistically significant. Results: We included 578 patients. Median age was 67 (interquartile range: 59-74) years, and 40% were female. Among all patients, 226 (39%) were frail. Compared to fit patients, patients who were frail were older (median age: 70 vs. 65 years, P<0.001) and more likely to have International Staging System (ISS) III (vs. I/II) disease (47% vs. 27%, P<0.001) and ECOG performance status ≥2 (vs. 0 or 1) (45% vs. 17%, P<0.001). There was no difference in R-ISS III disease or presence of high-risk cytogenetic abnormalities between fit and frail patients. Median OS was 7.6 and 4.1 years in fit and frail patient, respectively (P<0.001). Physician assessed ECOG performance status was available for 268 patients. Among patients with ECOG performance status 0 or 1 (193 patients), 136 (70%) were fit, and 57 (30%) were frail. The OS was 8.3 and 4.6 years in the 2 groups, respectively (P=0.006) (table 2). On multivariate analysis including age, frailty status, and R-ISS stage (III vs. I/II), all were associated with OS with frailty's hazard ratio (HR): 1.4 (95%CI [1.1-1.8]), P=0.004; the HR was 1.4 (95%CI [1.1-1.9]), P=0.02, when analysis was restricted to patients ≥60 years. Among all patients, those who were married or in a committed relationship (474 patients) had improved survival (median OS: 7.0 vs. 3.7 years, respectively, P<0.001) compared to patients who were divorced/separated, widowed, or single (96 patients). On multivariate analysis, which included age, R-ISS III, frailty status, and relationship status, all were associated with OS. The HR for relationship status was 1.4 (95%CI [1.0-1.8]), P=0.0465. Conclusion: Frailty, defined by the deficit accumulation frailty index, is independently associated with decreased survival in patients with newly diagnosed MM. Being married or in a committed relationship is associated with improved survival independent of age, disease stage, and frailty.

Frail Multiple Myeloma Patients Deserve More Than Just a Score.

Frailty is a hot topic in the field of multiple myeloma (MM). Clinicians have realised that frail myeloma patients can struggle with treatment, resulting in dose reductions and treatment discontinuation, which risk shorter progression-free and overall survival. Efforts have focused on the validity of existing frailty scores and on the development of new indices to identify frail patients more accurately. This review article explores the challenges of the existing frailty scores, including the International Myeloma Working Group (IMWG) frailty score, the revised Myeloma Co-morbidity Index (R-MCI), and the Myeloma Risk Profile (MRP). We conclude that the missing link is for frailty scoring to translate into a tool useful in real-world clinical practice. The future of frailty scores lies in their ability to be woven into clinical trials, to create a robust clinical evidence base for treatment selection and dose modification, and also to identify a cohort of patients who merit additional support from the wider MM multidisciplinary team.

Correlation Amongst Scoring of Various Frailty Tools in Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Introduction: With the growing array of treatment options for multiple myeloma (MM) patients, it is important to individualize the approach at each point in the patient's treatment journey. Frailty scores such as the Revised Myeloma Comorbidity Index (R-MCI) can help match therapeutic intensity to patient fitness, particularly important in the elderly. The R-MCI has been prospectively validated in transplant patients and found to be predictive for PFS and OS outcomes. At our centre, we are enrolling patients deemed transplant-eligible by standard institutional criteria into a prospective study applying a variety of frailty tools, including objective measures of comorbidity/function and subjective measures based on patient self-assessment and physician opinion. These tools are applied at time of transplant clearance, not at diagnosis as previously studied, to take into consideration changes in frailty that occur during the initial treatment phase. The primary objective is to identify normative frailty scores at this timepoint and correlate with severity of transplant-related toxicity. In this analysis, we present data on the first 101 enrolled patients, reporting the various frailty scores and their inter-correlation. Patients and Methods: The first 101 consecutive MM patients preparing for autologous transplant (ASCT) and consented for the frailty study were included. Patients underwent comprehensive frailty assessments including: 1) objective measures of fitness [hand grip strength, 6-min walk test (6MWT), Timed Up and Go (TUG), 2) subjective measures of function (abbreviated Fried Frailty Phenotype Score (FFP), Rockwood Clinical Frailty Score, KPS, ECOG, HSCT-CI, ESAS), 3) scoring systems integrating both objective and subjective measures (R-MCI, International Myeloma Working Group geriatric assessment tool (IMWG-GAT), and 4) routine screening for organ function (creatinine clearance, serum albumin, hemoglobin, BNP, PFT, and cardiac imaging). Demographics including disease and treatment details were obtained from electronic medical records. Measures were evaluated with Chi-square/Fischer's exact test/Kruskal-Wallis test to assess the association between the various frailty scores. In addition, frailty scores were compared against R-MCI as baseline. All p values were 2-sided and p≥0.05 was considered statistically significant. Results: From Feb 2020 to July 2022, 101 patients consented for the frailty study and were included in this analysis. Patient characteristics and frailty scores are summarised in Table 1. ASCT was part of upfront treatment in 87 patients (86%), with 14 patients (14%) receiving salvage transplant at relapse. Median age was 63 years (35-75), with 9(9%) age 70 and above. In general, our transplant-eligible population tested well on most frailty scores, mostly falling within the fit or intermediate-fit categories, as expected. Notable exceptions were significantly poorer handgrip strength and 6MWT than observed in the literature. Only 2 of 101 patients in our analysis were able to walk >400 metres, a threshold for fitness cited in prior transplant studies. Most scoring systems in our analysis correlated in designating our cohort as "fit” or "intermediate fit". When using the transplant-validated R-MCI scores as our gold standard, we observed correlations with the IMWG-GAT and Rockwood scores (p=0.0014 and <0.0001 respectively). The simple-to-perform ECOG and HCT-CI indices also correlated highly with R-MCI.(Table 2) That said, the R-MCI lacked discrimination in our patient population, with almost all patients clustered into the fit or pre-fit categories (98/101; 98%). Conclusions: In this analysis of various frailty assessments applied at ASCT for MM, we report that most scoring systems correlated but generally lacked discrimination in this relatively fit cohort. Even the widely cited R-MCI which is validated in both myeloma and transplant, has limited utility in discriminating within this more homogeneously fit population. We will hence focus next on identifying scoring systems or individual tools that can further define the less fit or mildly frail within the "fit” category, allowing us to identify subgroups for medical optimization pre-ASCT. We also note that physical function testing such as handgrip and 6MWT may have limited utility in myeloma where disease-related disability may prevent full engagement. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

An objective assessment in newly diagnosed multiple myeloma to avoid treatment complications and strengthen therapy adherence.

In heterogeneous multiple myeloma (MM) patients treatment decisions are challenging. The hypothesis was that adaptation of treatment intensity (dose reduction [DR] vs. none) according to an objective risk score (revised-myeloma comorbidity index [R-MCI]) rather than physician judgement alone may improve therapy efficacy and avoid toxicities. We performed this study in 250 consecutive MM patients who underwent a prospective fitness assessment at our center, after having received induction protocols based on physicians' judgement. DR, serious adverse events (SAE), response, progression-free survival (PFS) and overall survival (OS) were compared in fitness (fit, intermediate-fit, frail), age (<60, ≥70 years [y]) and therapy intensity subgroups at baseline and follow-up. Fit and <60 y patients were mostly treated with full intensity, whereas frail and ≥70 y patients usually received DR. Hematological and non-hematological SAE were more frequently seen in frail versus ≥70 y patients. Dose adaptations were mainly necessary in frail patients. OS and PFS were similar in fit and intermediate-fit but significantly worse in frail patients (P=0.0245/P<0.0001), whereas in age-based subgroups, OS and PFS differences did not reach significance (P=0.1362/P=0.0569). Non-hematological SAE were another negative predictor for impaired OS and PFS (P=0.0054/P=0.0021). In the follow-up performed at a median of 11 months after the first fitness assessment, the R-MCI improved or remained stable in 90% versus deteriorated in only 10% of patients. In conclusion, separation by R-MCI/frailty-defined subgroups was superior to age-based subgroups and can be used to improve tailored treatment. Fitter patients benefit from intensive therapies, whereas frail patients bear a need for initial DR.

The limited use of autologous hematopoietic stem cell transplant for fit older patients with multiple myeloma in India: a retrospective analysis

BackgroundMultiple myeloma (MM) predominantly affects older patients; many of whom do not undergo autologous hematopoietic stem cell transplant (AHSCT) despite the associated survival benefits. This study was conceived to investigate the patterns of AHSCT among MM patients with due regard to their age and standardized fitness assessments.MethodsFitness scores as per the hematopoietic stem cell transplant-comorbidity index (HSCT-CI) and risk scores as per the revised-myeloma comorbidity index (R-MCI) of MM patients treated between January 2017 and December 2019 were analyzed to assess fitness for AHSCT. Proportions of patients who underwent AHSCT were calculated with regard to age and fitness for AHSCT.ResultsOf the 81 eligible patient records with a median age of 62 years, the HSCT-CI classified 79.6% and 77.8% of patients aged ≤65 years and >65 years as AHSCT eligible (p 1). Using the R-MCI, 96.3% and 81.5% of patients aged ≤65 years and >65 years, respectively, were classified as eligible for AHSCT (p 0.0381). Overall, patients aged ≤65 years underwent AHSCT with a greater frequency compared to those aged >65years (38.9 vs. 14.8%, p 0.0402). Irrespective of the age group, there was a statistically significant difference (p 0.0167) in terms of survival which favored those who underwent AHSCT.ConclusionsBoth the HSCT-CI and the R-MCI revealed that nearly 80% of patients aged >65 years were fit enough to receive AHSCT. However, far fewer patients of this age group underwent AHSCT. We propose that the routine inclusion of objective fitness assessment could ensure that fit older patients undergo AHSCT and thus do not miss out on the benefits of the same.

Evaluation of the frailty characteristics and clinical outcomes according to the new frailty-based outcome prediction model (Myeloma Risk Profile-MRP) in a UK real-world cohort of elderly newly diagnosed Myeloma patients.

The management of myeloma in the elderly is shifting its focus towards reducing the risk of under-treating fit patients and the risk of over-treating frail patients. Frailty assessment is required in this patient group in order to individualise treatment decisions. In addition to the proven prognostic values of the International Myeloma Working Group (IMWG) frailty score and the revised Myeloma Co-morbidity Index (R-MCI), a new easy-to-use frailty-based risk profile score (high-risk (i.e. frail), medium risk (i.e. intermediate-fitness) and low-risk (i.e. fit)) named Myeloma Risk Profile (MRP) was shown to be predictive of survival in the clinical trial setting. In this retrospective real-world study, we set out to evaluate the frailty characteristics and clinical outcomes according to the different MRP scoring algorithm categories (frail vs. intermediate vs fit), in a high risk cohort of elderly newly diagnosed myeloma patients treated with the fixed-duration triplet therapy VCD (bortezomib with cyclophosphamide and dexamethasone). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Out of 100 patients, 62 were frail, 27 were intermediate and 11 were fit, according to MRP scores. To enable meaningful comparisons between comparable numbers, subgroups analyses for ORR, OS, PFS, and AEs focused on frail (n = 62) versus intermediate or fit (n = 38) patients. The proportion of patients in each subgroup who were able to complete the planned course of treatment was (frail: 43.5% vs. intermediate or fit: 55.3%). A higher proportion in the frail subgroup discontinued therapy due to progressive disease (19.4% vs. 2.6%). Discontinuation due to toxicity was comparable across subgroups (14.5% vs. 15.8%), ORR in the total cohort was 75%, and this was comparable between subgroups (frail: 74.2% vs. intermediate or fit: 76.3%). There was a trend for a shorter median OS in the frail subgroup but without a statistical significance: (frail vs. intermediate or fit): (46 months vs. not reached, HR: 1.94, 95% CI 0.89–4.2, p = 0.094). There was no difference in median PFS between subgroups: (frail vs. intermediate or fit): (11.8 vs. 9.9 months, HR: 0.99, 95% CI: 0.61–1.61, P = 0.982). This cohort demonstrated a higher incidence rate of AEs in frail patients compared to those in the intermediate or fit group: patients with at least one any grade toxicity (85.5% vs. 71.1%), patients with at least one ≥G3 AE (37.1% vs. 21.1%). In conclusion, our study is to the first to evaluate clinical outcomes according to MRP in a high risk real-world cohort of patients treated exclusively with the proteasome inhibitor-based VCD therapy. Our study demonstrated a trend for worse OS in addition to worse AE outcomes in the frail group, but no difference in PFS with this fixed-duration therapy. MRP is an easy-to-use tool in clinical practice; its prognostic value was validated in the real-world in a large cohort of patients from the Danish Registry. Further evaluation of MRP in the real-world when continuous therapies are used, can further support the generalisability of its prognostic value in elderly myeloma patients.

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Simple SummaryDuring the course of their disease, almost all multiple myeloma patients experience one or more relapses. Treatment options for relapsed/refractory multiple myeloma (RRMM) have largely increased in the last decades. The choice of when and how to treat in the relapsed/refractory setting can therefore be challenging. Since multiple myeloma (MM) typically affects elderly people, it is of importance to include specific, frailty-related comorbidities in the choice of treatment. The aim of this review was to present an update on treatment options for patients with RRMM, under consideration of today’s available literature, current guidelines and patient-, disease- and treatment-related factors. We focused on geriatric assessments (GA) and frailty scores such as the revised myeloma comorbidity index (R-MCI), international myeloma working group (IMWG-) frailty index and others as these allow obtaining a more accurate picture of the individual patient constitution than the numerical age alone.Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, bone lesions). When choosing RRMM-treatment, the biochemical markers for progression and severity of the disease, dynamic of disease relapse, type and number of prior therapy lines, including toxicity and underlying health status, need to be considered, and shared decision making should be pursued. Objectively characterizing health status via geriatric assessment (GA) at each multiple myeloma (MM) treatment decision point has been shown to be a better estimate than via age and comorbidities alone. The well-established national comprehensive cancer network, IMWG, European myeloma network and other national treatment algorithms consider these issues. Ideally, GA-based clinical trials should be supported in the future to choose wisely and efficaciously from available intervention and treatment options in often-older MM adults in order to further improve morbidity and mortality.

Functional Assessment (FA) in Multiple Myeloma (MM) Patients Predicts Survival: Use of Most Valuable Comorbidity Scores and Functional Tests in a German Study Group (Deutsche Studiengruppe Multiples Myelom [DSMM]) Incentive

Introduction: Treatment options in Multiple Myeloma (MM) patients (pts) have substantially improved, but pts present with heterogeneous health status. Since the incidence of MM is increasing with age and the majority of pts is above 60 years, it is important to assess additional diseases and comorbidities. Measuring frailty, especially in older pts allows to identify those with an increased risk of treatment complications and impaired progression-free- (PFS) and overall-survival (OS). As MM interventions and therapy can be tailored, not only older, but also “intermediate-old” and younger MM pts may profit from such assessments. Therefore, a brief assessment of pts' functional, physiological and psycho-cognitive status was performed within this DSMM incentive, using 12 functional assessment (FA) tests and 5 established Comorbidity Indices (CI). The aim was to determine the most essential stratification for MM, to develop a meaningful, time-effective assessment arsenal for true estimation of pts' fitness and avoidance of both under- and overtreatment.Methods: We prospectively performed a FA in 301 consecutive newly diagnosed MM pts treated between 2011 and 2017. 12 functional tests comprised of the Karnofsky Performance Status (KPS), physician- and patient-rated fitness, Activity of daily living (ADL), Instrumental Activity of daily living (IADL), pain (VAS), Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), Timed Up and Go Test (TUGT), malnutrition, SF-12-Qualtiy of Life (QoL) Physical (PCS) and Mental Health Composite Scale (MCS). Additionally, 5 established CI were assessed: 1. International Myeloma working group (IMWG)-frailty index, 2. Revised Myeloma Comorbidity Index (R-MCI), 3. Charlson Comorbidity Index (CCI), 4. Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and 5. Kaplan-Feinstein-Index (KFI). In order to identify most valuable functional tests and CI, Kaplan Meier estimation and Cox regression for OS with backward variable selection were performed in order to determine which tests provided additional value for both IMWG-frailty index and R-MCI.Results: Pt characteristics were typical for tertiary centers. Median OS from the time point of assessment and median follow-up were 58 and 19 months, respectively. CI that grouped pts into significantly different risk groups for OS were the IMWG-frailty index, R-MCI and CCI, whereas both HCT-CI and KFI remained insignificant. Those CI that differentiated best between different risk groups were the IMWG-frailty index and R-MCI. 3-year-OS for good-, intermediate and high-risk pts using the R-MCI was 90%, 74% and 43% (p=0.0006) and via IMWG-frailty index 92%, 83% and 57% (p=0.0001), respectively. The 3-year-OS for good- vs. high-risk pts via CCI was 90% vs. 64% (p=0.0063). The 12 functional tests that significantly differentiated pts into different risk groups were the KPS with 3-year-OS for good- vs. high-risk pts of 89% vs 60% (p=<0.0001), physician-rated fitness of 80% vs. 66% (p=0.0085), patient-rated fitness of 82% vs. 64% (p<0.0036), ADL of 80% vs. 66% (p=0.0159), IADL of 78% vs. 48% (p=0.0036), pain of 78% vs. 66%, MMSE of 78% vs. 47% (p=0.0001), TUGT of 79% vs. 63% (p=0.0168) and SF-12 PCS of 86% vs. 66% (p=0.0091). GDS, malnutrition and SF-12 MCS tests proved insignificant. Backward selection with both IMWG-frailty index and R-MCI forced therein revealed 4 other tests to significantly complement these CI, namely the KPS, ADL, MMSE and SF-12 PCS.Conclusion: Our results suggest that our abbreviated FA, consisting of 2 CI (IMWG-frailty index and R-MCI) and 4 functional tests (KPS, ADL, MMSE, SF-12 PCS) constitutes a feasible, time-effective and highly diagnostic test set to estimate fitness and vulnerability in MM. Next steps include the automatic inclusion of the abbreviated assessment results into our MM-tumor board tool and pts' reports for high availability in medical discussions and therapy selection. Rather than focusing on pts' chronological age alone, our analysis aims to ultimately facilitate treatment decision and allow individualized treatment. DisclosuresLarocca:Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria. Engelhardt:German Cancer Aid (#11424): Other: Educational Grant; Janssen Cilag GmbH: Other: Educational Grant; Celgene GmbH: Other: Educational Grant; Amgen GmbH: Other: Educational Grant.

Navigating the Changing Multiple Myeloma (MM) Treatment Landscape: Real-World Data on Clinical Practice Patterns in 287 MM Patients Treated in and Outside German DSMM (Deutsche Studiengruppe Multiples Myelom) Study Group Trials

Introduction: Over the last decade MM diagnosis and therapy have greatly improved; notably due to an increasing number of “novel agents” (NA; e.g. PIs, IMiDs, mAbs, HDAC-, PD1/PD-L1-inhibitors). Anti-MM-therapy has gained complexity; orientation towards “state of the art” chemotherapy (CTx) protocols and international guidelines, as well as their continuous evaluation is highly important. According to the international literature, analyses of CTx management and particularly the use of novel substances have mainly been performed in the context of clinical trials (CT), therefore in a selected minority of patients (pts). In order to determine, whether guideline recommendations on MM therapy are thoroughly implemented in- and outside CT settings, we performed a real-world data analysis on clinical MM practice patterns. Substance use was analyzed in view of treatment lines and evaluated for “MM-pathway conformity”.Methods: We performed a detailed analysis of 287 myeloma pts treated at our University Medical Center, part of the DSMM study group in 2014/15. The pt cohort was defined using the hospital pharmacy and tumor documentation (TBD) databases. TBD analysis enabled the detailed acquisition of pt characteristics, such as age at initial diagnosis (ID), gender, Durie and Salmon (D&S) and International Staging System stage (ISS). Status of transplantation (Tx), comorbidity (via Revised Myeloma Comorbidity Index [R-MCI]), CT data, treatment line/cycle and the year of CTx application were collected using electronic medical records, TBD and CTx management tools. Basic data on therapy composition was collected for the years 2005 to 2017, separating two treatment periods for 1st, 2nd and 3rd-line therapy of 2005-2012 and 2013-2017. This cut-off was carefully chosen to discriminate best between NA- and non-NA-based regimens, and between first generation PI- (bortezomib (BOR) and IMiD-use (thalidomide (THAL), lenalidomide (LEN)) and second generation NA.Results: Pt characteristics were representative for tertiary centers with a median age of 63 years (27-89), 54% were 60-79 and 14% >80 years old. The male:female gender ratio was 58%:42% and ISS predominantly advanced (II/III:62%). Pts showed substantial comorbidities and were classified as fit, intermediate-fit and frail according to R-MCI in 33%, 56% and 11%, respectively. Of interest, 33% of pts could be enrolled in CTs and 88% received 1st line treatment at our center. 275 pts received 1st-line, 149 pts 2nd-line and 97 pts 3rd-line treatment (Fig.1). As expected, numbers of pts decreased with subsequent lines of treatment, albeit the median time to 2nd line therapy due to progression amounted to 2 years. As depicted in Fig.1, 1st line conventional CTx (cCTx) alone was rare and substantially declined over time from 12% 2005-2012 to 1% in 2013-2017. 200 pts (73%) were treated with BOR in 1st line, 63 of 106 reinduced pts received BOR in 2nd or 3rd line. IMiD 2nd and 3rd line treatment was also common within different regimens and the combination of 2 NA of both PI+IMiD increased over time (BOR+THAL, BOR+LEN). The use of second generation NA in 2nd and 3rd line treatment notably increased in 2013 to 2017 in line with their approval. Our analysis revealed that 44% of second generation NA protocols were administered outside CT settings, mainly due to tight inclusion and wide CT exclusion criteria. Maintenance was performed in 57% of pts, predominantly with LEN (60%) and within DSMM CT protocols.Conclusion: Our analyses demonstrate that NA combinations are used predominantly today, whereas the use of cCTx alone is substantially declining. While BOR plays an important role in induction, LEN was subsequently used for maintenance and in outpatient-regimens. BOR-reinduction as a validated treatment option is also reflecting the substantial amount of BOR-based protocols worldwide. A significant percentage of second generation NA are administered outside CT settings, representing the fast and effective implementation of guideline recommendations into the real-world clinical practice at our and other MM centers. Currently, we are assessing the percentage of pts discussed in our weekly MM tumorboard, the evidence level of therapeutic interventions, PFS and OS. Results will be shown at the meeting, including the comparison of our data with others in a detailed review of the literature. [Display omitted] DisclosuresEngelhardt:German Cancer Aid (#11424): Other: Educational Grant; Janssen Cilag GmbH: Other: Educational Grant; Celgene GmbH: Other: Educational Grant; Amgen GmbH: Other: Educational Grant.

Autologous Stem Cell Transplantation in Newly Diagnosed Elderly Multiple Myeloma Patients: A Single Centre Experience

Introduction: Multiple myeloma (MM) is a plasma cell malignancy that affects older adults with a median age at diagnosis of 70 years. Autologous stem cell transplantation (ASCT) in combination with novel agents is the standard of care for young patients with newly diagnosed MM. The safety and efficacy of High Dose Therapy (HDT) as upfront treatment in elderly patients remain still uncertain, because elderly patients age are frequently associated with increased comorbidities, compromised physical conditions and a suspected increased treatment-related toxicity. In our centre we analyzed the treatment-related toxicities and the outcome in a homogeneous cohort of newly diagnosed elderly MM patients treated with HDT approach.Methods: we retrospectively evaluated 16 newly diagnosed elderly MM patients, according to International Myeloma Working Group (IMWG). All of them were fit/low-risk according to revised Myeloma Comorbidity Index. Median age at diagnosis was 66 years (range 65-68 years), and at transplantation 67 years (range 65-69). The MM immunoglobulin subtypes were: 9 IgG k (56.25%); 1 IgG l (6.25%), 1 IgA k (6.25%), 1 IgA l (6.25%), 1 light chain l (6.25%) and 3 light chain k (18,75%). In 5 patients we detected extramedullary plasmocitoma. The revised International Staging System (R-ISS) stage was: I in 8 patients (50%), II in 5 cases (31.25%) and III in 3 patients (18.75%). FISH analysis was performed at diagnosis in all patients, we found standard-risk in 10 patients (62.5%), intermediate-risk in 3 cases (18.75%) and high-risk in 3 cases (18.75%). All patients had a normal renal function. Immunoparesis occurred in 13 patients (81.25%) at diagnosis. The induction therapy was bortezomib-based in association with dexamethasone (VD) with or without thalidomide (VTD). Radiotherapy was performed in extramedullary disease. The mobilization regimen included cyclophosphamide at different doses (2 to 4 gr/mq) followed by G-CSF. The conditioning regimen consisted of melphalan 140 mg/mq or 200 mg/mq given over two days. A short 2-month consolidation phase bortezomib-based was given three months post ASCT.Results: As induction therapy 8 patients (50%) received VD, the other 50% VDT. Five patients (31.25%) underwent radiotherapy. A median of 12.6x106/kg CD34+cells were collected after cyclophosphamide treatment. Melphalan 140 mg/mq conditioning regimen was administered in 10 patients (62.5%) and 200 mg/mq in 6 patients (37.5%). Seven patients (43.75%) received consolidation treatment. The overall response rate (ORR) to induction therapy (≥ PR) was 93.75% including 2 CR (12.5%), 7 VGPR (43.75%) and 6 PR (37.5%). The ORR after ASCT increased to 100%: 3 CR (18.75%), 11 VGPR (68.75%) and 2 PR (12.5%). Immunoglobulin recovery 1 year after ASCT occurred in 9 patients (69.23%) out of 13 with immunoparesis. Median time to neutrophil and platelet engraftment was 10 days (range 6-18 days). No significant difference in toxicity was found among the two groups (MEL140 vs MEL200). The non-hematological toxicities after ASCT (G3-G4) included infections in 8 patients (50%), gastrointestinal disorders in 8 cases (50%), and nervous system disorders (G3) in 7 cases (43.75 %). In 1 patient we observed cardiac toxicity (G2). The day-100 post ASCT treatment-related mortality (TRM) was 0%. During follow up we reported secondary malignancies in 2 cases (12.5%) and one therapy-related myeloid neoplasm (t-MDS) (6.25%). After a median follow up of 59.5 months (range 21-73.3 months) the median PFS was 16.7 months in MEL140 group vs 28.3 months in MEL200. The difference among these two groups was statistically significant (p= 0.04).Conclusions:our results suggest that ASCT is a safe and well-tolerated procedure in our small cohort of elderly and fit patients. We detected among the two regimens (MEL140 and MEL200) a similar profile of toxicities. The dose of Melphalan (MEL200) impacted on the duration of response and the PFS resulted significantly higher. According to literature we confirm that an accurate assessment of elderly patients performance status, comorbidities and myeloma characteristics (by means of R-MCI) at diagnosis can help to develop individualized risk-adapted treatment strategies to improve the outcome, especially in elderly MM patients even in the era of new and highly effective drugs. DisclosuresNo relevant conflicts of interest to declare.

Comparison of the prognostic significance of 5 comorbidity scores and 12 functional tests in a prospective multiple myeloma patient cohort.

Because of the various therapeutic options available for multiple myeloma (MM), remarkable interest exists today in individualized therapeutic concepts based on patients' fitness. The main objectives of this study were to compare different comorbidity scores and functional tests with respect to their impact on survival (overall survival [OS] and progression-free survival [PFS]); develop a time-efficient, MM-specific functional assessment (FA); and evaluate changes in patients' FA during treatment. The authors performed a prospective FA in 266 consecutive patients with MM at their initial diagnosis. This included 5 comorbidity scores and 12 commonly used geriatric functional tests. To evaluate changes in the course of treatment, the authors reassessed these 17 tests after ≥6 months. The entire analysis included 7327 FA tests. On the basis of univariate and multivariate Cox regression analyses, the authors identified 4 of the 17 evaluated scores and functional tests as most relevant: the Revised Myeloma Comorbidity Index (R-MCI), Activity of Daily Living (ADL), the Mini-Mental State Examination (MMSE), and the quality-of-life 12-Item Short Form Health Survey Physical Composite Scale (SF-12 PCS). These showed precise group differences for fit, (intermediate-fit), and frail patients in OS and PFS: the 3-year OS rates were 90%, 74%, and 43% via the R-MCI for fit, intermediate-fit, and frail patients, respectively (P = .0006); 80% and 66% via the ADL for fit and frail patients, respectively (P = .0159); 78% and 48% via the MMSE for fit and frail patients, respectively (P = .0001); and 86% and 66% via the SF-12 PCS for fit and frail patients, respectively (P = .0091). In follow-up analyses, 16 of 17 FA tests improved, mostly in younger patients (<70 years old) and responding patients (partial remission or better). Patients may recover from functional and physical limitations under applied MM therapy. The newly established MM-specific FA (via the R-MCI, ADL, MMSE, and SF-12 PCS) allows a precise evaluation of the prognosis and risk status in MM. Its use may improve treatment tolerability and should be validated to individualize MM treatment decisions in the future. The authors performed a prospective functional assessment (FA) in 266 consecutive patients with multiple myeloma at their initial diagnosis. On the basis of univariate and multivariate Cox regression analyses, the authors identified 4 of 17 initially evaluated scores and functional tests as most relevant: the Revised Myeloma Comorbidity Index, Activity of Daily Living, the Mini-Mental State Examination, and the quality-of-life 12-Item Short Form Health Survey Physical Composite Scale. The authors checked the stability of the final model by applying forward and stepwise selection. To evaluate changes in the course of treatment, they reassessed these 17 tests in 165 patients after ≥6 months: 16 of the 17 FA tests improved, mostly in younger patients (<70 years old) and responding patients (partial remission or better).

Physical activity is associated with less comorbidity, better treatment tolerance and improved response in patients with multiple myeloma undergoing stem cell transplantation

ObjectivesMultiple myeloma (MM) is the second most common hematological malignancy. Progression free survival (PFS) and overall survival (OS) have substantially improved, nonetheless MM usually remains incurable. Patients with active disease may be affected by numerous comorbidities, including fatigue, depression and osteolytic lesions, which influence their quality of life (QoL). Albeit, it is known that exercising is beneficial for patients' QoL, few clinical trials are available in patients with MM. We therefore aimed to compare comorbidities and clinical outcome in physically active and inactive patients with MM. Material and MethodsWe defined physical activity according to WHO criteria (150 min of moderate activity and two sessions of resistance training/week). We matched 53 physically active patients with 53 controls (for age, gender, cytogenetics, disease stage, and therapy) and compared the cohorts for incidence of comorbidities/MM symptoms (osteolytic lesions, anemia, infections, fatigue, depression, Revised-Myeloma Comorbidity Index [R-MCI]) and clinical outcome (treatment tolerance, responses to therapy, PFS and OS) in a retrospective audit. All patients were newly diagnosed with MM and received autologous stem cell transplantations (ASCT) between 2001 and 2017. ResultsPhysically active patients showed superior outcomes in R-MCI (p = 0.0005), fatigue (p = 0.0063), treatment tolerance (p = 0.0258) and hospital stays (p = 0.0072). Furthermore, they showed better treatment responses (p = 0.0366), especially complete remission (CR; p = 0.0018) as well as better OS and PFS. ConclusionPhysical activity in patients with MM undergoing ASCT seemed associated with better overall clinical outcome. Randomized clinical trials are required to understand the benefits and devise strategies for improving exercising among patients with MM.

A Study Highlighting the Limited Use of Autologous Hematopoietic Stem Cell Transplant for Fit Elderly Patients with Multiple Myeloma in India

BACKGROUND Autologous Hematopoietic Stem Cell Transplant (AHSCT) remains an important treatment for multiple myeloma (MM) despite the continuous addition of novel agents into the therapeutic armamentarium. Since MM is predominantly a disease of the elderly, a significant proportion of patients do not undergo AHSCT due to 'a perceived lack of fitness'. This retrospective study evaluates the patterns of AHSCT in MM patients with regards to age and objective fitness assessment as per standardized indices. METHODS: Records of all MM patients treated at our institute from January 2017 till December 2019 were utilized to collect data regarding age, survival duration, risk scores as per the Revised-Myeloma Comorbidity Index (R-MCI) and fitness scores as per the Hematopoietic Stem Cell Transplant-Comorbidity Index (HSCT-CI). Patients with low and intermediate R-MCI risk scores were regarded as 'fit for AHSCT'. Patients with HSCT-CI categorizations of 'fit' and 'intermediate fit' were regarded as 'fit for AHSCT'. Proportions were compared using the Fisher-Exact-Test with a significance cut-off of p&amp;lt;0.05. Survival data were compared with the Log-Rank test. RESULTS: Out of the 81 patients, 54 (66.7%) were aged ≤65 years &amp; 27 (33.3%) &amp;gt;65 years. The R-MCI classified 96.3% and 81.5% of patients aged ≤65 years and &amp;gt;65 years as AHSCT eligible, respectively (p 0.0381). The HSCT-CI classified a similar proportion of patients aged ≤65 years and &amp;gt;65 years as AHSCT eligible (79.6% vs. 77.8%, p 1). However, patients aged ≤65 years were offered AHSCT more frequently than those &amp;gt;65 years (57.4% vs. 29.6%, p 0.0207). Those aged ≤65 years underwent AHSCT more frequently than those &amp;gt;65 years (38.9% vs. 14.8%, p 0.0402). (Panel A, Figure-1). Those who underwent AHSCT had greater median survival (MS) compared to those who did not undergo AHSCT (MS not reached vs. 36 months, p 0.0023) (Panel B, Figure 1). Those who were offered AHSCT had greater MS compared to those who were not offered AHSCT (MS not reached vs. 36 months, p 0.033) (Panel C, Figure 1). The MS of patients classified as fit and intermediate fit as per the HSCT CI was significantly better than that of those classified as 'unfit' (p 0.0362) (Panel D, Figure 1). The MS of patients classified by the R-MCI as low risk was significantly better than that of those classified as 'intermediate and high risk' (p 0.0253) (Panel E, Figure 1). When the MS of overall patients aged ≤65 years was compared to that of those aged &amp;gt;65 years, there was no significant difference with the MS not reached in either group (p 0.0875) (Panel F, Figure 1). When the survival curves of four groups (aged &amp;gt;65 years who underwent AHSCT, aged &amp;gt;65 years who did not undergo AHSCT, aged ≤65 years who underwent AHSCT, and those aged ≤65 years who did not undergo AHSCT) were compared, there was a statistically significant difference favouring those who underwent AHSCT irrespective of the age group (p 0.0167) (Panel G, Figure 1). Conclusions: Both the R-MCI and HSCT-CI revealed that approximately four out of five patients aged &amp;gt;65 years were AHSCT eligible. This analysis of the patterns of AHSCT for MM in our institution revealed a bias against those aged &amp;gt;65 years, with fewer patients of this age group being offered AHSCT. It would hence be prudent to perform objective fitness assessments using validated indices so as to ensure that every patient fit enough to benefit from an AHSCT receives the same irrespective of his/her age. While it is well known that treatment availability and affordability are two major reasons for low rates of AHSCT in Low &amp; Middle Income Countries (LMICs), it can be said from our data that physicians' bias against advanced age could be another factor. These results strongly suggest that use of AHSCT in fit elderly patients in LMICs may further improve outcomes. Figure Disclosures No relevant conflicts of interest to declare.

Caring for older adults with multiple myeloma during the COVID-19 Pandemic: Perspective from the International Forum for Optimizing Care of Older Adults with Myeloma

The novel coronavirus (SARS-CoV-2, COVID-19) was first identified in the province of Wuhan, China in December 2019 [1], following the emergence of new cases of pneumonia of unknown etiology. Since then, the manifestations of COVID-19 infections have ranged from asymptomatic to severe respiratory infections, with increased morbidity in older adults including those with co-morbidities and cancer [2,3]. Presently, global mortality is reported at 4.7%, but this varies widely by location, from 0.7% in Germany to 10.8% in Italy [4]. As of April 13, 2020, the number of infections continues to rise well beyond the 1.9 million cases, and approximately 120,000 COVID-19-related deaths that have already occurred globally [5]. Multiple myeloma (MM) is a malignant plasma cell dyscrasia which predominantly affects older and often frail adults. Although tremendous gains have been made for older adults with MM, infections, including respiratory infections, significantly impact the rate of early mortality in these patients [6,7]. Furthermore, older adults with MM have age-associated vulnerabilities leading to heterogeneity in outcomes [8]. The complexity of caring for older patients have increased substantially during this pandemic, due to concern about their risk of severe morbidity of COVID19 infection. Optimal strategies for these patients will involve staging the malignancy/aging, while simultaneously considering the local prevalence of COVID-19 infection. Herein, we discuss strategies for the risk reduction of COVID-19 transmission, treatment stratification of anti-myeloma therapy and discussion regarding goals of care for older adults with MM during the COVID-19 pandemic.

Clinical outcomes and prognostic factors in patients with multiple myeloma in South Tyrol: a retrospective single-center analysis.

High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) as well as the introduction of novel agents (NA) significantly improved survival for patients with multiple myeloma (MM). A total of 150 unselected newly diagnosed MM patients treated at our institution from 1998 to 2017 were retrospectively analyzed. Median age at diagnosis was 69years (range 33-93years) with a median follow-up of 48.6months. The median overall survival (OS) for the entire cohort was 60.7months (range 0.3-280.1). Patients who received frontline HD-ASCT (p < 0.01) or NA-based first-line treatment (p = 0.043) had a significantly better OS. According to the revised Myeloma Comorbidity Index (R-MCI), patients were defined as fit (36.5%), intermediate-fit (44.5%), or frail (19%) with a significant difference in OS between these categories (p < 0.01). Multivariate analysis revealed R-MCI as an independent prognostic factor for OS (p < 0.01). Presence of subclinical amyloid deposits (A+) was detected in 18 out of 66 patients (27.3%) and significantly correlated with a serum free light chain (sFLC) ratio ≥ 100 (p = 0.01) and bone marrow plasma cell infiltration > 60% (p = 0.04). Furthermore, patients with A+ had significantly worse OS compared with their counterparts (p = 0.048). Our results corroborate the efficacy of both early HD-ASCT and the use of new agents as initial therapy of MM patients in "real-world" daily clinical practice. The R-MCI is an easily applicable tool to stratify MM patients and may support treatment decisions. The prognostic value of subclinical amyloid deposition should be validated within prospective studies.

Impact of Combining Frailty Assessment Systems to Select Elderly Myeloma Patients Eligible for Autologous Peripheral Blood Stem Cell Transplantation

Introduction The International Myeloma Working Group (IMWG)-frailty index (IMWG-FI) and revised myeloma comorbidity index (R-MCI) are multiple myeloma (MM)-specific frailty scoring systems, which the European Myeloma Network advocates to assess patient frailty, and to select goals and treatments including autologous stem cell therapy (ASCT). In Japan, patients &lt;65 years old are recommended to receive ASCT under the guidelines of the Japanese Society of Hematology, The Japan Society for Hematopoietic Cell Transplantation, and Japanese Society of Myeloma. However, some Japanese institutes perform ASCTs on MM patients ≥65 years old, although the eligibility criteria and the ASCT methods are variable, or depending on the attending physicians' experience and preference, and doctor-patient relationships. In our institute, 17 MM patients ≥65 years old received ASCT and their frailty at the time of ASCT was retrospectively analyzed. Methods We performed 51 ASCTs on 43 MM patients between April 2017 and June 2019. Seventeen patients were elderly, and 34 were younger. The conditioning regimens were melphalan 200 mg/m2 for younger and 140 mg/m2 for the elderly patients. Both groups received the same supportive therapy. Frailty was compared using the IMWG-FI, R-MCI, and Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), and the toxicity and efficacy of ASCT were retrospectively analyzed. Results The patients' ages at the time of ASCT were statistically different between groups (67.8 vs 57.8 years old, p&lt;0.001). The number of fit and intermediate-fit patients by IMWG-FI were 14 and 3 in the elderly group, and 28 and 6 in the younger group, respectively (p=1.0). Fit and intermediate-fit patients by R-MCI were 13 and 4 in the elderly group, and 27 and 7 in the younger group, respectively (p=1.0) (Table 1). No patients were classified as frail in either group by the IMWG-FI and R-MCI. The median scores (ranges) of HCT-CI were 1 (0-5) in the elderly group, and 1.5 (0-5) in the younger group (p=0.93). The number of CD34 positive cells harvested from peripheral blood was lower in the elderly than in the younger group (3.8 vs 5.4×106/kg, p=0.0027). For the elderly and younger groups, the infused CD34 positive cell count (2.4×106 vs 2.4×106/kg, p=0.87), days for neutrophil (11 vs 11 days, p=0.87) and platelet engraftments (15 vs 15 days, p=0.7), and the hospitalization periods (26 vs 27 days, p=0.27) were not statistically different. Both groups had no transplantation-related deaths, similar rates of the non-hematologic adverse events (grade ≥3), an improvement in response (≥very good partial response (VGPR); 49% vs 74%, p=0.003) before vs after ASCT. Post-ASCT ≥VGPR rates were similar between the elderly and younger groups (73% vs 75%, p=1.0). Discussion We safely performed ASCT for elderly MM patients. The frailty status of the younger and elderly groups were the same, as evaluated by the IMWG-FI, R-MCI, and HCT-CI. Our eligibility criteria for MM patients for ASCT was by biological and not chronological age. Thus, the prospective assessment of elderly MM patients by these tools may enable us to evaluate the risks of elderly ASCT, through which elderly ASCT-eligible cases can be selected. Eleven of the 17 elderly patients were termed fit by the IMWG-FI and R-MCI, and scored 0-3 by HCT-CI, 6 of whom were 0-1. Five patients were intermediate-fit by either IMWG-FI or R-MCI, with 0-3 by HCT-CI. Only 1 patient was intermediate-Fit by both IMWG-FI and R-CMI, and was 5 by HCT-CI (Table 1). Based on our data, we propose a stratification system that can determine ASCT eligibility in elderly MM patients. The elderly patients regarded fit by IMWG-FI and R-MCI with 0-1 by HCT-CI could be stratified as Low Risk for elderly ASCT. In addition, the frail patients by IMWG-FI or R-MCI or &gt;3 by HCT-CI could be stratified as High Risk ineligible for elderly ASCT. Other patients could be Intermediate-Risk for elderly ASCT. Further studies are needed to determine the adequate melphalan dosage such as 200 mg/m2 for 65-69 year-old patients, and 140 mg/m2 for 70- Conclusion We retrospectively analyzed the elderly patients receiving ASCT using two MM-specific frailty indices and HCT-CI. We propose a new stratification system to select elderly patients eligible for ASCT. ASCT issues for the elderly MM patients should be examined prospectively. Disclosures No relevant conflicts of interest to declare.

The Revised Myeloma Comorbidity Index (R-MCI) As a Promising Approach for Predicting Overall (OS)- and Progression-Free (PFS) Survival and Optimizing Therapy Strategies in Multiple Myeloma (MM) Patients (pts) - Comparative Analysis of 5 Comorbidity Indices (CI), Including Retro- and Prospective Applicability

Introduction: MM is considered an incurable disease. Due to the improvement in long-term survival of MM pts with innovative therapy strategies, the necessity of including comorbidities and biological fitness status to treatment options has significantly increased over the last years. However, elderly pts still remain to benefit to lesser extends revealing lower PFS and OS rates, show more treatment-induced side effects and a lower quality of life. Therefore, it is inevitable to include an objective frailty assessment into MM guidelines to avoid under- and overtreatment. Since no CI has been widely established yet, selection process should include the capability of assessing a retro- and prospective baseline for comparing CI results among available data sets. This analysis compared 5 internationally well-discussed CIs regarding OS and PFS prediction and tested if these CIs can be reliably assessed retro- and prospectively. Methods: This prospective study was performed for 347 consecutive pts treated at our center, analyzing OS and PFS for the R-MCI, IMWG-, CCI, Mayo- and MRP-scores: the factors that are included in each individual score are shown in Table 1. For each CI, pts were divided into 3 risk groups (low-, intermediate-, high-risk), except for the CCI with possible designation into low- and high-risk group only. Based on these risk groups, OS and PFS were estimated by Kaplan Meier Method and compared via log rank test. Additionally we compared this above mentioned prospective cohort with a prior study including 749 pts treated at our center (Haematologica 2017;102:910-21). For this cohort we now performed a retrospective analysis with 4 of the latter CIs to analyze differences in risk group distribution within these two cohorts via Chi Square tests. Since there was missing laboratory data for the UK-MRP-score in the retrospective cohort, it was excluded from the latter analysis. Results: Pts' characteristics were typical for tertiary centers with a median age of 65 years (yrs). Median Follow-up was 36 months, median OS was not reached and PFS was 34 months. All 5 CIs could divide pts into risk groups with significantly different OS (p&amp;lt;0.05). The difference in 3yr OS for high- and low-risk group using the R-MCI was 43% and via IMWG- and Mayo-score 37% and 70% respectively. Minor distinction for OS prediction was achieved by CCI and MRP with only 25% and 20% difference. For the MRP, the 3-yr-OS rate for frail (59%) exceeded that of intermediate pts (50%), moreover, this group comprised only low numbers (n=8). In analogy, the difference in 3yr PFS amounted to 48% for the R-MCI vs. 40% and 59% for IMWG- and Mayo-scores, respectively. Here again the CCI and MPR showed lowest PFS differences with only 20% and 27% between high- and low-risk groups (Table 1). Comparing the pro- and retrospective analyses via Chi-Square tests, only the R-MCI showed comparable results for the risk group distribution in both cohorts (p=0.26) with 26% vs. 27%, 60% vs. 55% and 14% vs. 18% in low-risk, intermediate-risk and high-risk groups, respectively (Table 1). Respective results for IMWG and CCI scores showed that significantly more patients were defined as low-risk in the retrospective than in prospective cohorts with 41% vs. 30% for the IMWG and 65% vs. 47% for the CCI, respectively (p&amp;lt;0.001). The results for the Mayo-score revealed that 13% of the retrospective cohort were classified as high-risk as compared to 8% of the prospective cohort (p=0.0209). Conclusions: To our knowledge this is the first large prospective comparative analysis of 5 internationally discussed CIs. Our results show an excellent separation into risk groups with different OS and PFS via R-MCI, IMWG and Mayo-scores, whereas via CCI and Mayo-score to a much lesser extent. The results of this analysis reinforce the multifunctionality and convenience of using one MM-CI, like the robustly tested and repeatedly validated R-MCI. Further unique features of the R-MCI are the pro- and retrospective applicability in daily clinics, a user-friendly homepage and the future perspective of extended use, e.g. for tailoring therapies, which is currently investigated and which results will be shown at the meeting. Disclosures Wäsch: Takeda: Consultancy; Pfizer: Consultancy; Amgen: Other: travel, Research Funding; Sanofi: Consultancy; Gilead: Other: travel, Research Funding; Novartis: Consultancy; Celgene: Other: travel, Research Funding; Sanofi: Other: Travel, Research Funding; Gilead: Consultancy; Jazz: Other: travel, Research Funding; Amgen: Consultancy.