scholarly journals Clinical Features and Predictive Factors of Early Mortality in Patients with MM Outside of Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5593-5593
Author(s):  
Hiroki Kobayashi ◽  
Yoshiaki Abe ◽  
Daisuke Miura ◽  
Kentaro Narita ◽  
Akihiro Kitadate ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Predictive Factors ◽  
Real World ◽  
Medical Center ◽  
Early Mortality ◽  
Novel Agents ◽  
Predictive Score ◽  
Ecog Ps

Abstract Background Novel agents such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have improved the overall survival of patients with newly diagnosed multiple myeloma (NDMM) over the last decade. However, early mortality (EM) remains a serious obstacle for a portion of the patients despite receiving novel agents. The report based on clinical trials showed that age, International Staging System (ISS), lactate dehydrogenase (LDH) levels, and high-risk cytogenetic abnormalities (CA) predict EM due to myeloma progression. The result, however, may differ from real-world settings because the patients of clinical trials are relatively younger and have fewer health problems, and the major cause of EM is not only disease progression, but also infections and comorbidities. In this study, we retrospectively analyzed the clinical variables that affected EM in patients with multiple myeloma (MM) in the real-world setting in the novel agent era. Patients and Methods The study population consisted of 238 consecutive patients with NDMM between January 2008 and April 2018 at Kameda Medical Center, Japan. All patients were administered PI- or IMiD-based combined chemotherapy in the frontline setting. Patients diagnosed with smoldering MM and solitary plasmacytoma and who did not receive treatment were excluded in this study. Early mortality was defined as death within two years after diagnosis due to any cause. Comorbidities were evaluated according to the Charlson Comorbidity Index (CCI). Instrumental Activities of Daily Living (IADLs) were retrospectively scored based on medical records. IADLs were assessed by the percentage of the score because the full score of IADLs is different between men and women. High-risk CA was defined by the presence of t(4;14), t(14;16), and del(17p). Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.2. Ethical considerations This study was approved by the institutional review board of Kameda Medical Center and conducted according to the principles of the Declaration of Helsinki. Results The median age of the patients was 72.2 years, and the median observation period was 40.8 months. Fifty patients (21.3%) died within two years. The major causes of mortality were myeloma progression (36%), infection (22%), and comorbidities (20%). Baseline involved free light chain (iFLC), LDH > normal range, and high-risk CA were not statistically significant between the patients with or without EM. There were significant differences in age, reduction in iFLC on day 7 from the baseline, ISS stage, Revised-ISS stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥3, CCI score ≥4, and the percentage of IADL scores between the two groups (Table1). Next, we analyzed IADL scores and the reduction in iFLC on day 7 because these variables were not assessed in previous studies. Receiver-operating characteristic curve analysis showed that the best cutoff values were 50% for IADL scores and 65% for the reduction in iFLC on day 7. Univariate analysis suggested that the factors associated with EM were age >75 years, ISS stage 3, CCI score ≥4, ECOG-PS ≥3, IADL <50%, and iFLC reduction >65% on day 7. The multivariate analysis showed that CCI score ≥4 [odds ratio (OR), 2.43; 95% confidence interval (CI), 1.11-5.32; p=0.027], IADL score <50% (OR, 3.31; 95% CI, 1.42-7.70; p=0.006), and iFLC reduction >65% on day 7 (OR, 3.20; 95% CI, 1.45-7.07, p=0.004) were independent predictive factors for EM (Table2). Thus, the EM predictive score was established according to following variables: CCI score ≥4, IADL score <50%, iFLC reduction >65% on day 7, and ISS stage 3. Sixty patients were categorized with high scores (score ≥3), and half of the patients with high scores died within two years, while only 10% of the patients with low scores (score <3) died within two years (p<0.001). Conclusion One-fifth of the patients with NDMM died within two years due to myeloma progression, infection, and comorbidities. Our results suggested that high-risk CA and high levels of LDH did not have predictive value for EM in patients with NDMM outside of clinical trials. The presence of high CCI scores, low IADL scores, and decreases in iFLC (>65%) on day 7 from the baseline were independent prognostic factors, which could reflect both patient and disease factors. The combination of the CCI score, IADL score, ISS stage, and early reduction in iFLC may help in the identification of EM. Disclosures No relevant conflicts of interest to declare.

scholarly journals Erythropoietin Level and Percentage of Urinary Albumin Are Important for Renal Recovery in Patients with Multiple Myeloma Receiving Novel Agents

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5571-5571
Author(s):  
Hiroki Kobayashi ◽  
Yoshiaki Abe ◽  
Daisuke Miura ◽  
Kentaro Narita ◽  
Akihiro Kitadate ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Predictive Factors ◽  
Light Chain ◽  
Medical Center ◽  
Urinary Albumin ◽  
Renal Recovery ◽  
Novel Agents ◽  
Response Criteria ◽  
Kappa Light Chain ◽  
Renal Response

Abstract Background Renal impairment (RI) is one of the most common complications of multiple myeloma (MM), and is a major cause of morbidity and mortality. Monoclonal free light chain (FLC) is associated with most RI in patients with MM, and previous reports showed that early reduction of FLC is associated with renal recovery. Novel agents including bortezomib and immunomodulatory drugs (IMiDs) contribute to early reduction of FLC, leading to renal recovery. However, some patients developed irreversible RI despite the use of novel agents, and the factors that predict renal recovery other than early reduction of FLC remain unclear. This study retrospectively analyzed the clinical variables that affect renal recovery in patients with RI receiving novel agents. Patients and Methods The study population consisted of 235 consecutive patients with newly diagnosed MM (NDMM) between January 2008 and April 2018 at Kameda Medical Center, Japan. All patients were treated with bortezomib or IMiD-based combined chemotherapy in the frontline setting. Nine patients who received less than 2 courses of chemotherapy were excluded because it was difficult to assess renal recovery. RI was defined as an estimated pretreatment glomerular filtration rate (eGFR) of <50 ml/min/1.73 m2. We used the simplified Modification of Diet in Renal Disease formula to calculate eGFR. Maximum renal response was evaluated according to International Myeloma Working Group (IMWG) renal response criteria. Major renal response was defined as achieving PRrenal and CRrenal. Erythropoietin (EPO) was measured, if a patient had anemia (male: hemoglobin [Hb] <12.0 g/dl, female Hb <11.0 g/dl). Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.2. Ethical considerations This study was approved by the institutional review board of Kameda Medical Center and conducted in accordance with the principles of the Declaration of Helsinki. Results The median patient age was 72.2 years and the median observation period was 40.8 months. Moderate-to-severe RI (eGFR <50 mL/min/1.73 m2) was identified in 104 patients (46.5%). The median eGFR was 27.9 ml/min/1.73 m2. The percentage of patients with light-chain only isotype was 28.8%, and 57.7% of the patients had kappa light chain. According to IMWG renal response criteria, 54.8% of patients achieved major renal response, including PRrenal 4.8% and CRrenal 49.0%. Baseline involved FLC, reduction of FLC, light chain-only isotype, and kappa light chain type were not statistically significant between patients with or without major renal response. There were significant differences in age, calcium, EPO, and percentage of urinary albumin excretion between responders and non-responders (Table). Receiver operating characteristic curve analysis showed that the best cutoff values were 24.6 mIU/ml for EPO and 24.7% for the percentage of urinary albumin (Figure). The factors associated with major renal response included age <75 years, calcium, percentage of urinary albumin <25%, and EPO ≥25 mIU/ml. The multivariate logistic regression analysis showed that age <75 years [Odds ratio (OR)=9.86; p=0.005], calcium (OR=8.94; p=0.010), percentage of urinary albumin <25% (OR=15.5; p=0.002), and EPO ≥25 mIU/ml (OR=18.4; p<0.001) were independent predictive factors for renal recovery. When patients were divided based on the percentage of urinary albumin <25% and level of EPO ≥25 mIU/ml, the proportion of those who achieved major renal recovery was significantly different among 3 groups (both urinary albumin <25% and EPO ≥25 mIU/ml vs. either urinary albumin <25% or EPO ≥25 mIU/ml vs. neither urinary albumin <25% nor EPO ≥25 mIU/ml: 84.2% vs 32.3% vs. 6.0%, p<0.001). Conclusion Our results indicate that early reduction of FLC could have less predictive value for renal recovery compared to that in previous reports because early FLC reduction could be obtained in almost all patients irrespective of improvement in renal function. However, the level of serum EPO and the percentage of urinary albumin emerged as positive predictive factors for renal recovery in patients with RI receiving novel agents. The combination of these 2 variables could predict renal recovery more precisely. Disclosures No relevant conflicts of interest to declare.

Treatment Outcomes and Toxicity Profile of Kyprolis in Multiple Myeloma: A Single Institution Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Richa Thakur ◽  
Nina Kohn ◽  
Monique Hartley-Brown
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Disease Progression ◽  
Real World ◽  
Cell Transplant ◽  
Single Center ◽  
The Real ◽  
Overall Response ◽  
Increased Risk

Background: Survival outcomes of Multiple Myeloma (MM) patients have significantly increased with recent advances in treatment. In the past decade several agents have been FDA approved due to improvement in the progression-free survival (PFS). Kyprolis is an irreversible proteasome inhibitor (PI) that was first approved in 2012 for treatment of MM. The real-world use of Kyprolis in treatment of MM is important to assess. Aim: The primary objective of this study is to evaluate the real-world outcome in overall response rates (ORR) for MM patients treated with Kyprolis. This was a retrospective study at a single center site in the Northwell Health system, evaluating patients at the Monter Cancer Center. Secondary objectives include determining the PFS, and adverse side effects (ADEs), including cardiovascular and renal toxicities of MM patients treated with Kyprolis at our institution. Methods: We retrospectively analyzed the charts of patients with a known diagnosis of MM who were treated with Kyprolis between January 1, 2013, and December 31, 2018. Baseline patient demographics such as age, gender, MM stage at diagnosis based on the Revised International Staging System (R-ISS) criteria, cytogenetics and fluorescence in situ hybridization (FISH), prior treatment regimens, autologous stem cell transplant (ASCT) were collected. Statistical methods included percentage calculations of baseline characteristics. Time to progression was measured from start of treatment to disease progression. PFS was calculated as a mean from initiation of treatment to the time point when progression was first noticed. Results: We identified 66 patients who fit our criteria of inclusion in this study. The median age was 65 years (Range 48 to 84). Based on the R-ISS staging, 7 (10%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) were stage III. Based on cytogenetics 31% of the patients were classified as high risk (defined as having a 13q deletion, t (4,14), del(17p), t (14,16), or gain 1q). There were 32.3% of the patients with hyperploidy. A subset of patients was heavily pretreated with approximately 18.2% receiving more than 4 treatment lines prior to initiation of Kyprolis and 22.7% having received 3 prior lines. 42.4% of patients received 2 prior lines of MM- directed therapy. Prior treatments mainly included immunomodulatory agents (IMiDs) such as Lenalidomide and Proteosome Inhibitors (PIs) such as Bortezomib. Cyclophosphamide in combination with Bortezomib and dexamethasone (CyBorD) was also a frequent pre-treatment regimen. In regards to ASCT, 42.4% of patients had undergone prior ASCT before Kyprolis therapy. The overall response rate was 77.2%, with 6.2% having obtained a complete response (CR) as defined by the International Myeloma Working Group response criteria. Thirty-five (53%) patients terminated Kyprolis due to disease progression or intolerance and underwent a change in their treatment. There were 10 patients (15%) who required ASCT after receiving Kyprolis in the setting of progression of disease. The majority of patients that progressed received Daratumumab (40%) or Pomalidomide (46%). Regarding ADEs, grade 2 hypertension was noted in 14% of all patients, acute renal failure (ARF) in 17% of patients, dyspnea in 25.4%, gastrointestinal (GI) toxicity in 16.3%, and fatigue in 40.8% of patients who received Kyprolis. The median PFS on Kyprolis at this site was 6.96 months. Conclusion: Our study shows that Kyprolis improved PFS in patients with MM. However, these patients are at increased risk for cardiac and renal toxicity. This study varies from published findings of clinical trials. Our patients had a higher percentage of high-risk cytogenetics as compared to those in the ASPIRE trial. About 90% of patients in the ASPIRE study had an ECOG status of 0 or 1, which was better than the average seen in our patient population. These two factors may have contributed to a lower observed PFS than that initially observed in the clinical trials. Second, this is a retrospective single center study, with inherent biases that may result in additional variance. The proportion of grade 2 ADEs were comparable to the frequencies reported in the ASPIRE and ENDEAVOR trials. The toxicities noted in this study reinforce the importance for community oncologists to be aware of these issues. Early prevention and management may impact quality of life, response, or tolerance to Kyprolis therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characteristics and Outcomes of Non-Transplanted Patients with Newly Diagnosed Multiple Myeloma (NDMM) Initiating Treatment with Bortezomib, Lenalidomide, and Dexamethasone (VRd) As First-Line of Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3782-3782
Author(s):  
Rohan Medhekar ◽  
Tao Ran ◽  
Alex Z. Fu ◽  
Sharmila Patel ◽  
Shuchita Kaila
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Real World ◽  
Index Date ◽  
Newly Diagnosed ◽  
First Line ◽  
The Real ◽  
Real World Setting ◽  
Line Of Therapy ◽  
Ecog Ps

Abstract Introduction: In the US, bortezomib, lenalidomide, and dexamethasone (VRd) is one of the preferred treatment regimens in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) based on the results from the phase 3 Southwest Oncology Group (SWOG) S0777 study. Although the efficacy of VRd in transplant-ineligible or -deferred NDMM patients was demonstrated in SWOG S0777, clinical trials have strict eligibility criteria that may not translate to the real-world. There is limited real-world data on the characteristics and outcomes of non-transplanted patients with NDMM treated with VRd, especially in older, frail patients with comorbidities. This study aimed to address these knowledge gaps by evaluating the characteristics and outcomes of patients with NDMM who received VRd as first-line of therapy (LOT) in US oncology practice. Methods: This retrospective observational study included patients from the Flatiron Multiple Myeloma Core Registry who received VRd as first LOT between November 1, 2015 and February 28, 2021. The index date was defined as the first observed record of the VRd regimen. Non-transplanted patients were defined as those who did not receive a stem cell transplant (SCT) from the diagnosis date to the index date. Patients were excluded if they were &lt;18 years of age on index date; were enrolled in a clinical trial; had other malignancies prior to the index date; had a diagnosis of amyloid light-chain amyloidosis prior to the index date; or had a SCT prior to index date. Demographics, clinical characteristics, and outcomes were assessed in the overall study cohort and among specific subgroups: older adults (≥75 years of age on index date); frail patients (frailty score ≥2, calculated using age on index date, Charlson Comorbidity Index during the pre-index period, and Eastern Cooperative Oncology Group performance status [ECOG PS] score on the closest date to the index date ≤90 days prior to and ≤7 days after the index date, patients with missing ECOG were not excluded); patients with high-risk cytogenetics, and patients with acute renal impairment ([RI], serum creatinine &gt;2 mg/dL on the closest date to the index date or having diagnosis codes of ICD-9-CM 584.5-584.9, ICD-9-CM 586, ICD-10-CM N17.0-2, N17.8-9, and N19, measured ≤90 days prior to and ≤7 days after the index date). Duration of therapy was measured as the time between the index date and end of the LOT. Progression-free survival (PFS) was measured as time between the index date and disease progression or death, whichever occurred first. PFS did not account for treatment discontinuation for reasons other than progression or death. Disease progression was defined as a clinically meaningful increase in serum M-protein, urine M-protein, or the free light chain ratio according to the International Myeloma Working Group criteria. PFS was analyzed using the Kaplan-Meier method. Results: A total of 2342 eligible NDMM patients treated with VRd as first LOT were identified, with a median follow-up of 21.0 months. A majority of patients were ≥65 years (64.3%), with the mean (SD) age at index date being 67 (±10) years. Most patients were male (53.3%), had International Staging System [ISS] stage I/II (48.4%; 33% missing) and the ECOG PS score 0/1 (63.5%; 22% missing). Of the 2342 patients, 597 (25.5%) patients were categorized as older adults (≥75 years of age); 1122 (47.9%) as frail; 374 (16.0%) as patients with high-risk cytogenetics; and 250 (10.7%) as patients with RI. About 28% of the patients received a SCT within 1-year of the index date. The median duration of therapy was 5.6 months. The median PFS for the overall study group was 33.2 months. Median PFS was substantially shorter for patients who were ≥75 years of age (22.8 months), were frail (28.7 months), had high-risk cytogenetics (25.1 months), or had RI (25.1 months) (Figure). Conclusions: The majority of patients with NDMM treated with VRd in the real-world setting were aged ≥65 years, were ISS stage I or II, had an ECOG PS score of 0 or 1, and had standard-risk cytogenetics. Median PFS observed in the real-world setting was shorter than that observed in the SWOG S0777 clinical trial. Patients who were ≥75 years of age, were frail, had high-risk cytogenetics, or had RI demonstrated shorter median PFS than patients in the overall study population. Alternate treatment options with demonstrated efficacy in the older, frail, and transplant ineligible patients are available. Figure 1 Figure 1. Disclosures Medhekar: Janssen: Current Employment. Ran: Janssen Scientific Affairs, LLC: Current Employment. Fu: Janssen: Current Employment. Patel: Janssen: Current Employment. Kaila: Janssen Scientific Affairs, LLC: Current Employment. OffLabel Disclosure: Bortezomib, and lenalidomide are both FDA approved agents for treating multiple myeloma. The combination of bortezomib, lenalidomide, and dexamethasone is commonly used in clinical practice and is listed as a preferred regimen in NCCN guidelines.

scholarly journals What Is New in the Treatment of Smoldering Multiple Myeloma?

2021 ◽  
Vol 10 (3) ◽  
pp. 421
Author(s):  
Niccolo’ Bolli ◽  
Nicola Sgherza ◽  
Paola Curci ◽  
Rita Rizzi ◽  
Vanda Strafella ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Early Treatment ◽  
Individual Case ◽  
Symptomatic Disease ◽  
Plasma Cell Neoplasm ◽  
Smoldering Multiple Myeloma ◽  
Wide Range ◽  
Critical Issues

Smoldering multiple myeloma (SMM), an asymptomatic plasma cell neoplasm, is currently diagnosed according to the updated IMWG criteria, which reflect an intermediate tumor mass between monoclonal gammopathy of undetermined significance (MGUS) and active MM. However, SMM is a heterogeneous entity and individual case may go from an “MGUS-like” behavior to “early MM” with rapid transformation into symptomatic disease. This wide range of clinical outcomes poses challenges for prognostication and management of individual patients. However, initial studies showed a benefit in terms of progression or even survival for early treatment of high-risk SMM patients. While outside of clinical trials the conventional approach to SMM generally remains that of close observation, these studies raised the question of whether early treatment should be offered in high-risk patients, prompting evaluation of several different therapeutic approaches with different goals. While delay of progression to MM with a non-toxic treatment is clearly achievable by early treatment, a convincing survival benefit still needs to be proven by independent studies. Furthermore, if SMM is to be considered less biologically complex than MM, early treatment may offer the chance of cure that is currently not within reach of any active MM treatment. In this paper, we present updated results of completed or ongoing clinical trials in SMM treatment, highlighting areas of uncertainty and critical issues that will need to be addressed in the near future before the “watch and wait” paradigm in SMM is abandoned in favor of early treatment.

scholarly journals Comprehensive Geriatric Assessment in Consecutive Newly-Diagnosed Elderly Multiple Myeloma Patients in China: A Multicentered, Prospective, Non-Interventional Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5493-5493
Author(s):  
Yuan Yao ◽  
Dehui Zou ◽  
Aijun Liao ◽  
Xiaoxia Chu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Geriatric Assessment ◽  
Real World ◽  
Comprehensive Geriatric Assessment ◽  
Newly Diagnosed ◽  
Frail Patients

Background: Multiple Myeloma (MM) is a disease of the elderly, whose prognoses are highly heterogeneous. Hence International Myeloma Working Group (IMWG) proposed geriatric assessment (GA) in 2015, including daily activity and comorbidity status, to better discriminate between fit and frail patients (Palumbo et al, 2015). However, IMWG recruited patients from clinical trials instead of real world practices. Therefore we studied GA in elderly MM patients consecutively in China, along with other perspectives which are known to be problematic in elderly population that were previously left unnoticed, such as nutrition status, risk of cognitive impairment, risk of depression, and quality of life. Aim: Our study centers on the feasibility to perform a more comprehensive geriatric assessment (cGA) in elderly MM patients, current cGA status in elderly MM patients in China, and the cGA difference between Chinese patients and patients in the IMWG study. Method: From August 2017 to April 2019, we continuously recruited 336 newly diagnosed elderly (age ≥ 65) MM patients from 21 centers in China. cGA was performed at diagnosis, after treatment cycle 1, after cycle 4, and 1 year after treatment. cGA includes physical conditions (ECOG), activities of daily living (ADL), instrumental ADL (IADL), mini-nutritional assessment (MNA-SF), geriatric depression scale (GDS), mini-mental state examination (MMSE), quality of life (SF-36) and Charlson comorbidity index (CCI). Staging was assessed at baseline (International Staging System (ISS) & Revised ISS) and hematological responses were evaluated along with each cGA timepoint. Results: We pool-analyzed data of 336 newly-diagnosed elderly MM patients. The median age was 70 (range 65-88) and 25.5% of patients were older than 75 years. 336 (100%) patients were able to complete cGA, and median assessment time was 40 minutes (range 20-70). Upon diagnosis, only 34% and 37.5% of patients had full ADL and IADL respectively. 38.5% of patients had moderate to high risk of depression (GDS ≥ 6). 13.2% of patients were malnourished (MNA-SF ≤ 7), while 46.3% of patients were at risk of malnutrition (8 ≤ MNA-SF ≤ 11). 41% of patients had at least one comorbidity (CCI ≥ 1). 45.7% of patients had moderate to intermediate risk of cognitive impairment (MMSE ≤ 26). Grouping by IMWG-GA index, our study identified 59.9% patients in frail group (vs 39% in IMWG study), 15.8% in intermediate (vs 31% in IMWG) and 24.3% in fit (vs 30% in IMWG). 69% of patients received proteasome inhibitor-containing regimens and 20.7% of patients received lenalidomide-containing regimens. Best hematological responses in fit and intermediate groups were better than responses in frail group (≥ PR rate: 88.5% in fit, 94.4% in intermediate vs 77.5% in frail). Median follow up time was 10 months. To date, 215 (64%) patients have finished the cGA after cycle 1; 164 (48.8%) patients have finished the cGA after cycle 4; 91 (27.1%) patients has finished all 4 planned cGA and improvements in cGA were observed in the majority of these patients. Conclusion: Our study showed significant CGA heterogeneity in elderly MM patients. Even in the IMWG-GA "fit" group, nutrition, depression and cognitive impairment remain problems. Frail patients took up a larger proportion in Chinese elderly MM patients compared to IMWG study. Our study strongly justifies the necessity for cGA in elderly patients with MM, more so in the real world MM patients than in the clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Multiple Myeloma in Hispanics Is Associated with Better Survival Than Non-Hispanic African Americans and Whites: Analysis from a Large Single Center Minority Rich Cohort

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3601-3601 ◽  
Author(s):  
Gurbakhash Kaur ◽  
Mateo Mejia Saldarriaga ◽  
Ana Acuna-Villaorduna ◽  
Mohammad Kazemi ◽  
Sakshi Jasra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
African Americans ◽  
Medical Center ◽  
The United States ◽  
Novel Agents ◽  
Serum Lactate Dehydrogenase ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Montefiore Medical

Abstract Background: Multiple Myeloma (MM) represents 1.8% of all new cancers in the United States and is the second most common hematologic malignancy in the US with 30,000 new cases/year. The highest incidence is amongst African Americans (AA) (SEER, 2018). Increased use of autologous stem cell transplant (AHSCT) as well as introduction of proteasome inhibitors (PIs) and immunomodulatory agents (iMiDs) have led to an improvement in overall survival (OS) from 35.6% between 1998-2001 to 50.7% in 2008-2014 (Child et al. 2003; Pulte et al. 2014). Despite these improvements, outcomes in MM are heterogeneous and are influenced by sociodemographic factors like race and ethnicity, disease biology (laboratory markers, cytogenetics) and access to transplantation (Al-Hamadani, Hashmi, and Go 2014; Ailawadhi et al. 2016). Several large population-based studies report that Hispanics have low stem cell utilization rates, limited access to novel therapeutics and clinical trials as well (Ailawadhi et al. 2018; Costa et al. 2015; Schriber et al. 2017; Pulte et al. 2014). Hence, outcomes for Hispanics and AA lag behind non-Hispanic Whites as well (Pulte et al. 2014). We wanted to evaluate outcomes of MM patients at Montefiore Medical Center where AA and Hispanics have access to novel agents and therapeutics, and most of whom hail from a poor socio-economic status. Methods: We obtained a cohort of patients diagnosed with MM between 1/1/2000-12/31/2017 from the Montefiore Medical Center Cancer Registry database via Clinical Looking Glass software. Socio-demographic characteristics including self-reported ethnicity, date of diagnosis, histology, laboratory parameters (hemoglobin (Hgb), creatinine (Cr), albumin (Alb), serum lactate dehydrogenase (LDH)) within 30 days of diagnosis were obtained. Ethnicity and race variables were condensed to Hispanics, Non-Hispanic Whites (NHW) and Non-Hispanic African Americans (NHAA). Charlson comorbidity score and its age-adjusted version were calculated. Primary payor (Medicaid, Medicare, private insurance or self-pay) was identified for each patient. Descriptive statistical analysis was performed using STATA 15.1 statistical software. OS was estimated using the Kaplan-Meier method and HR and corresponding 95% confidence intervals (CI) were estimated using the cox proportional hazard model. All the variables in the Cox proportional hazard ratio model fulfill the proportional hazard assumption. Results: We identified 1630 patients during the study period; 1502 patients were available for analysis (Table 1) The mean age of diagnosis was 66 years, and NWH were diagnosed at older age when compared to Hispanics or NHAA (71 vs 64 vs 66, p=0.001) respectively. Hispanics had a higher proportion of Medicaid affiliation. The baseline mean Hb (p=0.02), Cr (p=0.02) and LDH (p=0.09) were different; however this difference is unlikely to be clinically relevant (Table 1). Median survival for the cohort was 63 months (95% CI: 59-69). Hispanics had better mean OS (118 months, (95% CI 96-128) as compared to NHW (49 months, 95% CI 40-68)) and NHAA (60 months, 95% CI 53-66) and others (32 months, 95% CI 21-46) (Figure 1). After controlling for age at diagnosis, gender, socioeconomic status, modified Charlson age score, race had a statistically significant impact on the outcome, with NHW (HR-2.01) and NHAA (HR 1.77) having poorer survival when compared to Hispanics (P<0.001). The results did not change after excluding the unknown group. Increasing age, Charlson score, earlier time period of diagnosis and male sex were independently associated with death (Table 2). Primary payor was not independently associated with worse outcomes. Conclusion The study cohort is significantly different to prior reports, with a higher rate of NHAA and Hispanics. Hispanics had a higher percentage of Medicaid as primary payor. Contrary to prior reports, we show that with access to novel agents and transplantation, MM in Hispanics has a better OS than AA and NHW. We also show that NHAA (41%) despite being diagnosed at a younger age than NHW continue to have poorer outcomes than Hispanics. Further characterization including risk stratification and cytogenetics is underway to identify factors leading to better and worse outcome in Hispanics and AA respectively. Disclosures Janakiram: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

How I Treat High-risk Multiple Myeloma

Blood ◽  
2021 ◽  
Author(s):  
Elena Zamagni ◽  
Simona Barbato ◽  
Michele Cavo
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Specific Drug ◽  
Improve Quality

Survival of multiple myeloma (MM) has significantly improved over the last decade; however, a composed group of patients (15-20%), named high-risk (HR) MM, still experience reduced survival. Both tumor biology and suboptimal/absent responses to therapy may underlie HR definition and a clear uniform identification of risk factors is crucial for a proper management of these patients. In biologic-HRMM, MRD negativity attainment and sustain, inside and outside BM, should be the primary goal and therapy should be adapted in patients with frailty to reduce toxicity and improve quality of life. MM treatment has traditionally been tailored on age and more recently frailty or comorbidities, but very rarely on the biology of the disease, mainly because of the lack of a clear benefit derived from a specific drug/combination, inhomogeneity in HR definition and lack of data coming from prospective, properly designed clinical trials. Some attempts have been successfully made recently in this direction. In this review, we are discussing the current different definitions of HR and the need for a consensus, the results of available trials in HR patients and the way through risk-adapted treatment strategies. For this purpose, we are proposing several clinical cases of difficult-to-treat patients throughout different treatment phases.

Real-World Experience with Minimal Residual Disease Testing with Next Generation Flow Cytometry and Functional Imaging in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
David Böckle ◽  
Paula Tabares Gaviria ◽  
Xiang Zhou ◽  
Janin Messerschmidt ◽  
Lukas Scheller ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
High Risk ◽  
Functional Imaging ◽  
Real World ◽  
Research Funding ◽  
Residual Disease ◽  
Focal Lesions ◽  
High Risk Disease ◽  
Minimal Residual

Background: Minimal residual disease (MRD) diagnostics in multiple myeloma (MM) are gaining increasing importance to determine response depth beyond complete remission (CR) since novel agents have shown to induce high rates of deep clinical responses. Moreover, recent reports indicated combining functional imaging with next generation flow cytometry (NGF) could be beneficial in predicting clinical outcome. This applies in particular to the subset of patients suffering from relapsed/refractory multiple myeloma (RRMM) who tend to show a higher incidence of residual focal lesions despite serological response. Here, we report our institutions experience with implementing both functional imaging and NGF-guided MRD diagnostics in clinical practice. Methods: Our study included patients with newly diagnosed multiple myeloma (NDMM) and RRMM achieving VGPR, CR or sCR. Bone marrow aspirates were obtained for MRD-testing according to IMWG 2016 criteria. Samples were collected between July 2019 and July 2020 and analyzed with NGF (according to EuroFlowTM guidelines) at a sensitivity level of 10-5. Results were compared to functional imaging obtained with positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI). High-risk disease was defined as presence of deletion 17p, translocation (14;16) or (4;14). Results: We included 66 patients with NDMM (n=39) and RRMM (n=27) who achieved VGPR or better. In patients with RRMM the median number of treatment lines was 2 (range 2-11). Fifteen patients suffered from high-risk disease. Median age at NGF diagnostics was 64 years (range 31-83). Among patients achieving VGPR (n=27), CR (n=10) and sCR (n=29) seventeen (26%) were MRD-negative by NGF testing. CR or better was significantly associated NGF MRD-negativity (p=0.04). Notably, rates of NGF MRD-negativity were similar among patients with NDMM (28%) and RRMM (26%). Even some heavily pretreated patients who underwent ≥ 4 lines of therapy achieved MRD-negativity on NGF (2 of 9). Functional imaging was performed in 46 (70%) patients with DW-MRI (n=22) and PET (n=26). Median time between NGF and imaging assessment was 2 days (range 0-147). Combining results from imaging and NGF, 12 out of 46 (26%) patients were MRD-negative with both methods (neg/neg). Three patients displayed disease activity as measured with both, imaging and NGF (pos/pos). Twenty-nine of the remaining patients were MRD-positive only according to NGF (pos/neg), while two patients were positive on imaging only (neg/pos). More patients demonstrated combined MRD-negativity on NGF and imaging (neg/neg) in the NDMM setting than in RRMM (32% versus 19%). We also observed that 30% of the patients with high-risk genetics showed MRD-negativity on both imaging and NGF. Of note, none of the patients with very advanced disease (≥4 previous lines) was MRD-negative on both techniques. Conclusion In the clinical routine, MRD diagnostics could be used to tailor maintenance and consolidation approaches for patients achieving deep responses by traditional IMWG criteria. Our real-world experience highlights that MRD-negativity can be achieved in patients suffering from high-risk disease and also in late treatment lines, supporting its value as endpoint for clinical trials. However, our data also support MRD diagnostics to be combined with functional imaging at least in the RRMM setting to rule out residual focal lesions. Future studies using MRD for clinical decision-making are highly warranted. Disclosures Einsele: Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rasche:Celgene/BMS: Honoraria; GlaxoSmithKline: Honoraria; Oncopeptides: Honoraria; Skyline Dx: Research Funding; Janssen: Honoraria; Sanofi: Honoraria.

scholarly journals Early mortality in elderly patients undergoing treatment for multiple myeloma in real-world practice

2018 ◽  
Vol 46 (6) ◽  
pp. 2230-2237
Author(s):  
Jun Xia ◽  
Lingling Wang ◽  
Xin Zhou ◽  
Jing Wang ◽  
Huan Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Elderly Patients ◽  
Real World ◽  
Staging System ◽  
Early Mortality ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
International Staging System ◽  
High Lactate

Objectives This study was performed to analyze the risk factors for early mortality (EM) in elderly patients undergoing treatment for multiple myeloma (MM) in real-world clinical practice. Methods Retrospective data from 108 elderly patients who were newly diagnosed with MM from January 2007 to July 2015 were analyzed in a single hematology center. EM was defined as death of any cause within 12 months after diagnosis. A multivariate regression model was used to evaluate EM. Results EM occurred in 16 (14.8%) elderly patients with newly diagnosed MM. The most common cause of death was infection (10/16, 62.5%). In the multivariate analysis, only an age of ≥75 years, International Staging System (ISS) stage III disease, and high lactate dehydrogenase concentration were significantly and independently associated with EM. Conclusion Our results suggest that infection is the leading cause of EM in elderly patients with MM. An age of ≥75 years, ISS stage III disease, and a high lactate dehydrogenase concentration are significant predictors of EM. We should further target this higher-risk patient population to define personalized therapy with which to improve outcomes.

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