Racial Disparities in the Utilization of Recommended Supportive Care Among Patients with Multiple Myeloma in the United States

Abstract Introduction: Patients with Multiple Myeloma (MM) are living longer due to therapeutic advancements. With improving MM outcomes, supportive care measures focused on optimizing quality of life and minimizing treatment-related toxicities have become more relevant. Patients with MM report high rates of bone pain, skeletal-related events and infections for which bisphosphonates, influenza vaccination, and antiviral prophylaxis have been recommended. The extent to which these supportive care measures are used during routine clinical practice and the factors predicting utilization remain unknown. Methods: We selected older adults (age >65 years) diagnosed with MM between 2008-13 from the Surveillance Epidemiology and End Results-Medicare linked database. We excluded patients diagnosed at autopsy or by death certificate, those without continuous Medicare Parts A and B coverage from 12 months prior to diagnosis through death or end of study (12/31/2014). Additionally, we required continuous Part D claims from 12 months prior to diagnosis to 2 years after diagnosis. We required patients to receive anti-myeloma therapy and survive the first full flu season after diagnosis. Outcomes of interest included proportion of patients receiving guideline concordant supportive care therapy defined as 1) bisphosphonate therapy (zoledronic acid or pamidronic acid) within first 12 months after diagnosis, 2) influenza vaccination in the first flu season after diagnosis, and 3) receipt of antivirals (acyclovir, valacyclovir) among patients receiving bortezomib therapy. We estimated a multivariable logistic regression model for each outcome to evaluate potential predictors of supportive care use including patient characteristics (age, gender, race/ethnicity, comorbidity, disability status, diagnosis of CKD, socio-economic status, year of diagnosis), provider volume/experience (number of MM patients treated during a 12 month look back), and facility type (hospital outpatient vs community). Results: A total of 1,569 Medicare beneficiaries met our eligibility criteria. The median age was 74 years with 47% male and 73% non-Hispanic whites. Only 66% of Medicare beneficiaries on active MM therapy received bisphosphonates within 1 year of diagnosis. 53% of patients received influenza vaccination in the first flu season following diagnosis, and 44% received antiviral prophylaxis while receiving bortezomib therapy. Sensitivity analysis with and without pre-existing chronic kidney disease showed that 48% and 72% received bisphosphonates respectively. In the multivariate analysis, predictors of bisphosphonate non-usage included increasing age, (odds ratio [OR] for 85+ years 0.37; 95% confidence interval [CI] 0.23-0.58 compared to 66-69 years), non-Hispanic black and Hispanic ethnicity (OR 0.51; 95% CI 0.34-0.76 and OR 0.56; 95% CI 0.35-0.91 respectively compared to whites), and higher comorbidity index (for Elixhauser index of 3+ OR 0.41, 95% CI 0.29-0.57 compared to 0). Significant predictors of flu shot non-usage included non-Hispanic black ethnicity (OR 0.49; 95% CI 0.34-0.70 compared to whites), living in West (OR 0.53; 95% CI 0.38-0.75 compared to Midwest), having Medicaid dual coverage (OR 0.66; 95% CI 0.49-0.89) and lower comorbidity burden (For Elixhauser index of 3+ OR 1.44; 95% CI 1.07-1.93 compared to 0). Meanwhile, predictors of antiviral prophylaxis non usage included earlier years of diagnosis (global P<0.01, with increasing OR for more recent years), and higher comorbidity burden (For Elixhauser index of 3+ OR 0.40; 95% CI 0.24-0.67 compared to 0). Conclusion: We found significant under-utilization of supportive care measures focused at bone health and infection prevention among elderly adults with MM in the US. Similar to prior work evaluating utilization of novel MM therapies and transplantation, we found significant racial disparities in receipt of MM supportive care. Future studies should seek to identify reasons for such under-utilization of supportive care during MM therapy so that appropriate interventions may be implemented. Disclosures Zeidan: Agios: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Incyte: Employment; Gilead: Consultancy; Ariad: Consultancy, Speakers Bureau; Abbvie: Consultancy; Pfizer: Consultancy. Podoltsev:Sunesis Pharmaceuticals: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astex Pharmaceuticals: Research Funding; Astellas Pharma: Research Funding; LAM Therapeutics: Research Funding; Celgene: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; Daiichi Snakyo: Research Funding; Celator: Research Funding. Gore:Celgene: Consultancy, Research Funding. Ma:Celgene: Consultancy, Research Funding; Incyte: Consultancy. Davidoff:Celgene: Research Funding. Huntington:Celgene: Consultancy; Bayer: Consultancy; Janssen: Consultancy.

Download Full-text

Patterns and Determinants of Cancer-Directed Drug Therapy in Medicare Beneficiaries with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.5926.5926 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5926-5926

Author(s):

Julia F Slejko ◽

Dorothy Romanus ◽

Daisuke Goto ◽

Eberechukwu Onukwugha ◽

Rahul Khairnar ◽

...

Keyword(s):

Multiple Myeloma ◽

African American ◽

Drug Therapy ◽

Research Funding ◽

Novel Therapies ◽

Medicare Beneficiaries ◽

Company Limited ◽

Comorbidity Burden ◽

Wholly Owned Subsidiary

Abstract Introduction: The introduction of novel therapies for multiple myeloma (MM) such as immunomodulatory drugs and proteasome inhibitors has led to considerable improvements in clinical outcomes, but the disease remains incurable. Both conventional and to a lesser extent novel therapies come with toxicity and treatment decisions need to be individualized based on factors such as age and comorbidities. Little is known about the frequency of drug therapy use in MM in real-world clinical practice. Objective: This study aimed to assess the prevalence of, and determinants associated with cancer-directed drug therapy among newly diagnosed symptomatic MM (NDMM) Medicare beneficiaries. Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER) registry and linked Medicare Claims (SEER-Medicare) data. We identified patients (>65 years) with an incident diagnosis of MM from 2007-2011 and associated claims from 2006-2012. Eligible patients had continuous enrollment in Medicare Parts A and B (12 months prior to) and in Part D (two months prior to) through six months post-diagnosis, or death (among patients who died within 6 months post diagnosis). Patients were required to have evidence of CRAB symptoms (hypercalcemia, renal insufficiency, anemia and bone disease) based on intravenous bisphosphonate utilization and ICD-9 diagnosis codes found in claims from six months pre- to one month post-MM diagnosis. Patients were followed until death; or censoring due to non-continuous Parts A, B and D enrollment after six months post diagnosis. We identified receipt of MM-directed therapies from Medicare claims during the follow up period using NDC and HCPCS codes for the following agents: bendamustine, bortezomib, cyclophosphamide, (liposomal) doxorubicin, interferon alfa-2b, etoposide, lenalidomide, melphalan, thalidomide, vincristine, and vorinostat, excluding dexamethasone monotherapy. The distribution of frontline therapies received within 90 days of diagnosis was characterized descriptively. Charlson Comorbidity Index (CCI) was derived based on claims within one year pre-diagnosis using a validated algorithm. Baseline characteristics among those who received any MM-directed treatment were compared to those who did not using t-tests and Chi-square tests for continuous and categorical variables, respectively. We also compared treatment rates in those diagnosed in an early (2007-2009) versus late period (2010-2011). Results: Of 3,391 patients with NDMM who met our inclusion criteria, 2,599 (76.6%) received MM-directed therapy during follow up. The median time until treatment initiation was 49 days (range: 0-2156). The treatment rate using a landmark analysis of patients who survived at least 6 months produced congruent results (77% treated patients). Those who initiated therapy were younger (mean age: 75.6 years) compared to untreated patients (mean age: 78.7 years, p<.001) and had a lower comorbidity burden based on the CCI (p<.001) (Table 1). Among those with CCI=0, 81.7% received treatment, while 79.0% of those with CCI=1 and 69.0% of those with CCI>1 received treatment (p<0.001). African American patients were less likely to receive therapy (68.6%) compared to Caucasians (77.7%) and those who were of another race/ethnicity (79.7%, p<0.001). The proportion of patients initiating treatment was highest in the West (78.8%) and Midwest (78.7%) versus the South (75.1%) and Northeast (72.6%) (p<0.001). Among patients receiving treatment, the following drug therapies were observed within three months of diagnosis: bortezomib (n=937 patients, 36.1%), lenalidomide (n=633,25.5%), melphalan (n=398, 15.9%), thalidomide (n=404, 15.5%) and cyclophosphomide (n=75, 2.8%). Of patients diagnosed in 2007-2009, 75.6% received MM-directed drug treatment compared to 78.0% of those diagnosed in 2010-2011 (p=0.12). Conclusion: Among NDMM patients, 23% did not receive MM-directed therapy. Treatment was associated with younger age and a lower comorbidity burden. Racial disparities, with a lower proportion of African American treated patients, and geographic variation in treatment rates were also observed. Future research is needed to assess the extent to which these determinants reflect patient preferences versus other factors, such as barriers to treatment access. Disclosures Slejko: PhRMA: Research Funding; Takeda: Research Funding; National Pharmaceutical Council: Research Funding. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Goto:Novartis AG: Research Funding. Onukwugha:IMPAQ International: Honoraria; Bayer Healthcare: Research Funding; Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Yong:Takeda: Employment.

Download Full-text

A Phase 1b Study Investigating Carfilzomib Administered Once Weekly in Combination with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.3322.3322 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3322-3322

Author(s):

Noa Biran ◽

David S. Siegel ◽

Jesus G. Berdeja ◽

Edward Faber ◽

Lasika Seneviratne ◽

...

Keyword(s):

Multiple Myeloma ◽

Research Funding ◽

Response Rates ◽

The United States ◽

Median Number ◽

Employment Equity ◽

Dose Evaluation ◽

Phase 1B ◽

Equity Ownership ◽

Grade 3

Abstract Background: The combination of carfilzomib with lenalidomide and dexamethasone (KRd) is approved in the United States and the European Union (EU) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Under these approvals, carfilzomib is administered twice weekly as a 10-minute intravenous (IV) infusion at a dose of 20/27 mg/m2. The phase 1/2 CHAMPION-1 study showed that once-weekly carfilzomib (20/70 mg/m2; 30-minute IV infusion) with dexamethasone was well tolerated and active in patients with RRMM (Berenson et al. Blood. 2016;127:3360−3368). We present initial results from the dose evaluation component of a phase 1b study (NCT02335983) assessing the safety and efficacy of once-weekly carfilzomib with lenalidomide and dexamethasone in patients with MM. Methods: This is an open-label, multicenter, dose-finding, phase 1b study.The primary objective of the study is to evaluate the safety and tolerability of a once-weekly KRd regimen. Secondary objectives included evaluation of the efficacy of a once-weekly KRd regimen. This study consists of 2 parts: a dose-evaluation component in patients with RRMM and a dose-expansion component in both RRMM and newly diagnosed MM (NDMM). Results from the ongoing dose-evaluation component in RRMM are presented. There were 2 planned dose cohorts in the dose-evaluation portion of the study: carfilzomib 56 mg/m2 KRd cohort (56 mg/m2) and carfilzomib 70 mg/m2 KRdcohort (70 mg/m2). All patients received carfilzomib (days 1, 8, and 15), lenalidomide 25 mg (days 1 - 21), and dexamethasone 40 mg (days 1, 8, 15 and 22) on a 28-day cycle (dexamethasone was not administered on day 22 for cycles 9+). Carfilzomib was administered as a 30-minute IV infusion: 20 mg/m2 on cycle 1 day 1 with escalation to the assigned dose level (56 or 70 mg/m2) thereafter. The protocol allowed 8 DLT-evaluable patients to be treated in the 56 mg/m2 and 70 mg/m2 cohorts. Response was assessed by investigators using International Myeloma Working Group Uniform Response Criteria. The data cutoff date for this analysis was June 23, 2016. Results: A total of 22 patients (56 mg/m2, n=10; 70 mg/m2, n=12) with a median age of 69 (range, 50-87) years were enrolled in the dose evaluation component of the study. The median number of prior regimens was 1 (range, 1 - 3) in both cohorts. There were no dose-limiting toxicities observed in any of the 15 dose-evaluable RRMM patients (56 mg/m2 cohort, n=8; 70 mg/m2 cohort, n=7). The median number of cycles started as of data cutoff was 9.5 (range, 3-15) in the 56 mg/m2 cohort and 6.0 (range, 2-9) in the 70 mg/m2 cohort. All patients experienced at least 1 treatment-emergent adverse event (AE). Grade ≥3 AEs occurring in ≥9% of patients, and any AE of interest are shown in Table 1. The only grade ≥3 AEs to occur in ≥2 patients (≥9%) were thrombocytopenia (56 mg/m2, n=2; 70 mg/m2, n=1), decreased neutrophil count (56 mg/m2, n=2; 70 mg/m2, n=1), anemia (56 mg/m2, n=2), and hypertension (56 mg/m2, n=1; 70 mg/m2, n=1). Although the numbers were small, there was no apparent difference in the incidence of dyspnea or hypertension between the 56 and 70 mg/m2 cohorts. Cardiac or renal failure of any grade was not reported at the time of the database snapshot in these patients with RRMM. Response rates after 4 cycles, as assessed by investigators, are shown in Table 2. Two patients in the 56 mg/m2 cohort did not complete 4 cycles: an 87-year old patient developed asymptomatic pulmonary hypertension (detected on a required echocardiogram study) and was taken off therapy; another patient withdrew consent. One patient in the 70 mg/m2 cohort had a partial response after cycle 1 but was found to have progressive disease in cycle 3 (listed as did not complete 4 cycles in Table 2). After 4 cycles, the response rates (investigator assessed), were 70% and 75% in the 56 and 70 mg/m2 cohorts (response assessment for 2 patients in the 70 mg/m2 cohort was missing at the time of the data cutoff). Conclusions: These results demonstrate that carfilzomib administered in a convenient once-weekly schedule in combination with lenalidomide and dexamethasone in patients with RRMM is safe with promising efficacy. The 70 mg/m2 dosing was selected for dose-expansion cohorts in RRMM and NDMM. An update on the expansion cohorts will be presented at the meeting. Disclosures Biran: Onyx: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Siegel:Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Merck: Honoraria; BMS: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Faber:Celgene: Speakers Bureau; Cardinal Health: Honoraria; Gilead: Consultancy, Honoraria. Seneviratne:Novartis Pharmaceuticals: Speakers Bureau. Alsina:Onyx: Speakers Bureau; Millenium Pharmaceuticals: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Onyx: Consultancy. Bensinger:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau. Kimball:Amgen Inc.: Employment, Equity Ownership. Zhou:Amgen Inc.: Employment, Equity Ownership. Landgren:BMS: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Download Full-text

Evaluation of Cardiovascular Comorbidities Among Patients with Multiple Myeloma in the United States

Blood ◽

10.1182/blood.v128.22.4794.4794 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4794-4794 ◽

Cited By ~ 4

Author(s):

Daniel J. Lenihan ◽

Ravi Potluri ◽

Hitesh Bhandari ◽

Sandip Ranjan ◽

Clara Chen

Keyword(s):

Multiple Myeloma ◽

Heart Disease ◽

Ischemic Heart Disease ◽

Cardiac Failure ◽

Coronary Atherosclerosis ◽

Research Funding ◽

Adult Population ◽

The United States ◽

Baseline Period ◽

Ischemic Heart

Abstract Background: Multiple myeloma (MM) is typically diagnosed in older adults, with a median age at diagnosis of 69 years and the majority diagnosed between ages 65 and 74 years. It might be expected that cardiovascular disease (CVD) would be common in this patient population but currently there is little data about CVD in this population. CVD events may be consequences of age-related comorbidities, CVD itself, or anti-MM treatment received. Anthracycline chemotherapy, certain proteasome inhibitors and immunomodulatory drugs have been reported to increase the risk of CVD complications. Objective: To determine the prevalence of CVD comorbidities among MM patients in the period prior to receiving anti-MM treatment as observed in a US claims database, in order to understand the magnitude of these risks in a 'real-world' practice setting. Methods: Patients with a diagnosis ICD-9 code for MM were identified in MarketScan Commercial and Medicare claims databases from 7/1/2012 to 9/30/2014. The index date was the first claim of an anti-MM drug in this period, which was preceded by a 6-month baseline period with continuous medical and prescription drug coverage and no claims for another anti-MM drug. CVD comorbidities included cardiac arrhythmia, cardiac failure, stroke, ischemic heart disease, hypertension, venous thromboembolism (VTE), angina, coronary atherosclerosis and myocardial infarction (MI). Descriptive statistics were used to measure and report demographics and patient characteristics. Prevalence of CVD in MM patients was adjusted for the age and sex profile of the general US population and compared with prevalence reported in the literature for the US population. Patients were also divided into subgroups according to the anti-MM regimen received, and the prevalence of CVD by subgroup was assessed. Results: 4,635 patients met the study eligibility criteria (median age 64 years, 57% male, 42% with Charlson Comorbidity Index ≥2). Of these, 28%, 21%, 32% and 18% were in the North Central, Northeast, South and West regions, respectively. During the baseline period, CVD was present in 66% (n=3,048) of patients with MM. Relative to the general US adult population, annual standardized prevalence rates in this MM population were 22.0, 12.0, 2.8, 2.1 and 1.1 times higher for arrhythmia, VTE, cardiac failure, coronary atherosclerosis and hypertension, respectively, while being 82%, 73% and 32% lower for angina, stroke and MI, respectively. It is possible that patients with a history of these acute CVD events were less likely to receive an anti-MM drug (Table). Further, the prevalence of baseline CVD events in patients receiving carfilzomib was 34%, 52%, 43%, 30% and 47% lower for arrhythmia, cardiac failure, ischemic heart disease, hypertension and coronary atherosclerosis, respectively, than in those not receiving carfilzomib. Conclusion: Compared with the general US adult population, patients with MM appear to have a higher prevalence of CVD comorbidities relevant to anti-MM treatment. The lower rates of baseline CVD events suggests clinicians may avoid using carfilzomib in MM patients who are at risk of CVD. Given the chronic nature of MM and the need for long-term care, CVD comorbidities should be ascertained and taken into consideration when selecting appropriate treatment to manage the clinical and economic burden associated with such conditions. Table Table. Disclosures Lenihan: BMS, Roche, Amgen (Consultancy); Takeda (Research Funding): Consultancy, Research Funding. Potluri:Janssen Research & Development, LLC: Other: Contracted to perform research; SmartAnalyst, Inc.: Employment. Bhandari:SmartAnalyst India Pvt. Ltd.: Employment. Ranjan:SmartAnalyst India Pvt. Ltd.: Employment. Chen:Bristol-Myers Squibb: Employment.

Download Full-text

Underutilization of guideline‐recommended supportive care among older adults with multiple myeloma in the United States

Cancer ◽

10.1002/cncr.32428 ◽

2019 ◽

Vol 125 (22) ◽

pp. 4084-4095 ◽

Cited By ~ 1

Author(s):

Smith Giri ◽

Weiwei Zhu ◽

Rong Wang ◽

Amer Zeidan ◽

Nikolai Podoltsev ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Multiple Myeloma ◽

Supportive Care ◽

The United States

Download Full-text

Stem Cell Transplant without Growth Factor In Multiple Myeloma: Engraftment Kinetics, Bacteremia, and Hospitalization.

Blood ◽

10.1182/blood.v116.21.3469.3469 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3469-3469

Author(s):

Morie Abraham Gertz ◽

Dennis Gastineau ◽

Martha Lacy ◽

Angela Dispenzieri ◽

Suzanne R. Hayman ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Growth Factors ◽

Growth Factor ◽

Research Funding ◽

Stem Cell Transplant ◽

The United States ◽

Median Number ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

Abstract Abstract 3469 Introduction: Stem cell transplantation is important in the management of multiple myeloma. In the United States, the standard of care is administration of growth factors to accelerate neutrophil recovery after stem cell transplant. The need for growth factors after transplant has not been investigated recently. Patients: We analyzed a cohort of 166 patients at our institution who underwent autologous transplant for multiple myeloma without receiving growth factors after transplant and compared them with 498 patients who received standard filgrastim beginning on posttransplant day 5. TABLE Results: A neutrophil count of 500/μL was achieved in a median of 12.5 days in patients receiving growth factor, compared with 13.5 days in those not receiving growth factor (P<.001) Fig 1. Platelet engraftment was identical (median, 14.5 days; P=.12) in both groups, despite a lower median number of CD34+ cells infused in patients who did not receive growth factors. Incidence of nonstaphylococcal bacteremia was identical in both groups. The median hospital stay was 3.5 days shorter in the group not receiving growth factor. Bacteremia impacted platelet but not neutrophil engraftment. Figure 2 Conclusion: It is feasible and reasonable to perform autologous stem cell transplant for multiple myeloma without administering growth factors. Estimated savings would be $4,600 for each transplanted patient. Growth factor administration is not required for a safe outcome and decreases the number and severity of some of the fluid-related complications after transplant such as acute respiratory distress syndrome, allergic reactions, alveolar hemorrhage, and rarely splenic rupture. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lacy:Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Download Full-text

Outcomes of Patients with Multiple Myeloma Harboring Gain/Amplification 1q in the Era of Modern Therapy

Blood ◽

10.1182/blood-2020-139780 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 45-46

Author(s):

Xiao Hu ◽

Cherng-Horng Wu ◽

Janet Cowan ◽

Raymond L. Comenzo ◽

Cindy Varga

Keyword(s):

Multiple Myeloma ◽

Survival Data ◽

Research Funding ◽

The United States ◽

Cell Transplant ◽

Newly Diagnosed ◽

Rank Tests ◽

Treatment Regimens ◽

The Impact ◽

Log Rank Tests

Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States. Fluorescence in-situ hybridization (FISH) is a popular tool to detect cytogenetic alterations which in turn, can contribute to the risk stratification of patients with MM. Gain or amplification of CKS1B gene at chromosome 1q21 region (gain 1q) is detected in 35-40% of newly diagnosed MM cases, and has been reported to be associated with inferior prognostic outcomes. It also frequently occurs with the deletion of CDKN2C at chromosome 1p32.3 (del 1p). There is a distinct lack of data on patients harboring this cytogenetic alteration in the era of novel agents. We sought to look at outcomes of this patient population at a single institution over the last 5 years. Methods: This retrospective study included all patients with MM as defined by the International Myeloma Working Group (IMWG) with available FISH studies identifying gain 1q between 01/01/2015 to 04/30/2020 at Tufts Medical Center. The study was approved by the Institutional Review Board. Baseline demography, disease characteristics, and treatment history were extracted from the electronic medical records. With death as primary event, overall survival (OS) was defined as the survival time from the discovery of gain 1q to death. Progression free survival (PFS) was defined as the time from discovery of gain 1q to first progression/relapse or death, whichever occurred first. Kaplan-Meier method was used to estimate survival data. Differences in survival between two groups were analyzed by log-rank tests. Multivariable cox regression adjusting for baseline characteristics and significant concurrent cytogenetic alterations were performed to explore the impact of treatment regimens on survival. Results: Of the forty-nine subjects included in this study, the age range was 39 to 85 years; 31 patients (63.3%) were over the age of 65 years, and 28 (57.1%) were male. Twenty-eight (57.1%) subjects with gain 1q were newly diagnosed while the remaining 21 (42.9%) were identified at relapse. Gain 1q was present in more than 20% of clonal cells in 73.5% of subjects and 29.6% had del 1p as well. Patients with gain 1q were more likely to have deletion 13q (65.3%) and hyperdiploidy (61.2%). Regarding treatment, 75.7% of patients received bortezomib, 70.3% received lenalidomide, 38.9% underwent autologous stem cell transplant (ASCT) and 64.9% received daratumumab. At the time of analysis, 41 patients were still alive. For the entire cohort, the estimated median OS was not reached (NR) (95% confidence interval [CI], 24.1-NR), and the estimated median PFS was 15.27 months (95% CI, 4.77-NR). In log-rank tests, presence of extra medullary disease was associated with shorter PFS (4.8 vs 24.1 months, P=0.003), while IGH abnormalities including complex IGH rearrangements or losses were associated with longer PFS (NR vs 8.2 months, P=0.046). Lenalidomide-based treatment was associated with prolonged OS (NR vs 17.2 months, P=0.048). Bortezomib-based therapy and upfront ASCT were associated with improved PFS (15.3 vs 4.7 months, P=0.036; NR vs 4.8 months, P =0.019 respectively). Further multivariate analyses adjusting for age, number of CKS1B copies, International Staging System stage, baseline creatinine, clone size, del 1p, lactate dehydrogenase, extra medullary disease, and IGH abnormalities revealed that administration of daratumumab after the discovery of gain 1q was associated with superior OS (Hazard Ratio [HR]=0.023x10^-2, 95% CI [0.002x10^-4, 0.299], P =0.022) compared with those not receiving this agent; both the use of bortezomib (HR=0.210, 95% CI [0.064, 0.687], P =0.010) and daratumumab (HR=0.126, 95% CI [0.015, 1.036], P =0.054) were associated with prolonged PFS. The use of lenalidomide or upfront ASCT lost prognostic benefit after adjusting for additional variables in multivariate models. Conclusions: The outcomes of MM patients with gain 1q were evaluated according to clinical characteristics, concurrent chromosomal alterations and treatment regimens. In our small cohort, daratumumab and daratumumab-bortezomib combination regimens were found to have a favorable impact on survival. Future prospective clinical trials with larger sample sizes are warranted to confirm the results and further improve the outcomes of MM patients with this cytogenetic alteration. Disclosures Comenzo: Amgen: Consultancy; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Caleum: Consultancy; Prothena: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding.

Download Full-text

The Incidence of Thromboembolism for Lenalidomide Versus Thalidomide in Older Patients with Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-110500 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 361-361

Author(s):

Ang Li ◽

Qian V. Wu ◽

Greg Warnick ◽

Edward N. Libby ◽

David A. Garcia ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Propensity Score ◽

Older Patients ◽

Research Funding ◽

The United States ◽

Immunomodulatory Drugs ◽

Newly Diagnosed ◽

Treatment Groups ◽

To Receive

Abstract Introduction: Chemotherapy backbones with immunomodulatory drugs have become the standard of care for the treatment of multiple myeloma (MM). Despite improved survival outcomes, thrombotic complications remain a concern especially in the older patients with co-morbidities. A meta-analysis showed that lenalidomide might be associated with lower rate of thromboembolism than thalidomide-containing regimen in patients with newly diagnosed MM with (0.7 vs. 2.6 per 100-patient-cycle) or without prophylaxis (0.8 vs. 4.1 per 100-patient-cycle) (JTH 2011;9:653). As thalidomide is still commonly used outside of the United States, it is important to understand if the thromboprophylaxis guideline is generalizable to all immunomodulatory drugs. However, no prior study has directly compared the thrombotic incidence between the two regimens while accounting for confounders. In the current propensity score weighted study, we have examined the incidence of venous (VTE) and arterial (ATE) thromboembolism and survival for older patients with newly diagnosed MM treated with lenalidomide- versus thalidomide-containing regimen. Methods: We performed a retrospective cohort study using the SEER-Medicare database and selected all patients 66 or older with newly diagnosed MM 2007 to 2013. Patients were included if they had a prescription of IMID within twelve months of diagnosis and complete enrollment for fee-for-service and prescription drug coverage. Patients were followed from the IMID index date until first VTE occurrence or death and they were censored for disenrollment from Medicare A/B/D, enrollment in health maintenance organization, or 12/31/2014. We defined VTE (including pulmonary embolism and deep vein thrombosis) and ATE (including acute stroke and myocardial infarction) using previously validated ICD-9-CM codes with positive predictive value of 75-95% (Thromb Res 2010;126:61, Am Heart J 2004;148:99, Stroke 2014;45:3219). We used inverse probability of treatment weighting (IPTW) to balance potential confounders (demographics, year of diagnosis, co-morbidities, concurrent medications) where a standardized difference (SD) of <0.1 was considered adequate balance. Weighted Kaplan-Meier curves and Cox models (HR) were used to compare overall survival. Weighted cumulative incidence curves and Fine-Gray subdistribution hazards models (SHR) were used to compare VTE and ATE incidence where death was treated as a competing risk. Variance was estimated via 200 bootstraps. Results: Among 2397 older MM patients that met the study criteria, 78% received lenalidomide (n=1863) and 22% thalidomide (n=534). There was a strong temporal trend of increasing lenalidomide use over time (Table 1). The lenalidomide group was more likely to receive bortezomib and lower dose of dexamethasone and less likely to receive anticoagulant prophylaxis. All confounders were balanced between the two treatment groups after IPTW. The 12-month incidence of VTE (10%) and ATE (5%) were similarly high in both groups (Figure 1a-b). Lenalidomide vs. thalidomide had a SHR of 1.11 (0.59-2.02) for VTE and a SHR 0.96 (0.45-1.98) for ATE. Overall survival was also not significantly different with a HR of 0.88 (0.60-1.18) for lenalidomide vs. thalidomide. Conclusion: In this propensity score weighted study of older patients with newly diagnosed MM, the cumulative incidences of VTE and ATE were similarly high in both lenalidomide- and thalidomide-treatment groups. The lack of difference in overall survival should be interpreted with caution as residual confounding such as severity of disease could influence this outcome. Our results suggest that appropriate risk stratification and vigilant thromboprophylaxis remain essential for MM patients receiving all types of immunomodulatory drugs. Disclosures Garcia: Retham Technologies LLC: Consultancy; Shingoi: Consultancy; Portola: Research Funding; Boehringer Ingelheim: Consultancy; Bristol Meyers Squibb: Consultancy; Janssen: Consultancy, Research Funding; Incyte: Research Funding; Daiichi Sankyo: Research Funding; Pfizer: Consultancy. Lyman:Amgen: Other: Research support; Halozyme; G1 Therapeutics; Coherus Biosciences: Consultancy; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

Phase 3b UPFRONT Study: Interim Results From a Community Practice-Based Prospective Randomized Trial Evaluating Three Bortezomib-Based Regimens in Elderly, Newly Diagnosed Multiple Myeloma Patients.

Blood ◽

10.1182/blood.v114.22.129.129 ◽

2009 ◽

Vol 114 (22) ◽

pp. 129-129 ◽

Cited By ~ 2

Author(s):

Ruben Niesvizky ◽

James Reeves ◽

Ian W Flinn ◽

Robert M. Rifkin ◽

Billy Clowney ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

The United States ◽

Survival Duration ◽

Community Based ◽

Advisory Committees ◽

Functional Scores ◽

Grade 3 ◽

D 20

Abstract Abstract 129 In this US community-based, randomized, open-label, multicenter phase 3b study, we compare the safety and efficacy of three highly active bortezomib (Velcade®, Vc)-based regimens for multiple myeloma (MM), Vc–thalidomide–dexamethasone (VcTD), Vc–dexamethasone (VcD), and Vc–melphalan–prednisone (VcMP), in previously untreated MM patients (pts) ineligible for high-dose therapy and autologous stem cell transplantation. Use of these regimens is supported by data from phase 3 studies; only VcMP has been investigated specifically in elderly pts. Here we present data from a pre-specified interim analysis (IA) of 210 pts performed after the first 70 pts in each arm had the opportunity to complete four cycles of therapy. Pts with symptomatic, measurable MM were randomized (1:1:1) to receive 49 weeks of therapy: 24 weeks (eight 21-day cycles) of induction with VcD (Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [Cycles 1–4)], days 1, 2, 4, 5 [Cycles 5–8]), VcTD (Vc 1.3 mg/m2, days 1, 4, 8, 11; T 100 mg/d, d1-21; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [Cycles 1–4), days 1, 2, 4, 5 [Cycles 5–8]) or VcMP (Vc 1.3 mg/m2, days 1, 4, 8, 11; M 9 mg/m2 and P 60 mg/m2, day 1–4, every other cycle), followed by 25 weeks (five 35-day cycles) of maintenance with Vc alone (1.6 mg/m2, days 1, 8, 15, 22). Prophylactic aspirin, full dose warfarin, or low molecular weight heparin was administered to the VcTD arm unless medically contraindicated.The primary endpoint is progression-free survival; secondary endpoints include overall survival, duration of response, time to next therapy, quality of life (QoL) using the EORTC QLQ-C30 questionnaire, safety and tolerability, and efficacy (CR/nCR, VGPR, PR, and ORR). Responses were assessed by investigators using central laboratory data, applying the International Myeloma Working Group uniform criteria. An Independent Data Monitoring Committee (IDMC) assessed safety, tolerability, response rates and QoL data to determine which two of the three arms should continue enrolling pts. Pts in the VcD, VcTD, and VcMP arms had median ages of 74, 73, and 72 years, respectively; 83%, 58%, and 73% had ISS stage ll/lll and 21%, 22% and 32%, respectively, were non-Caucasian. In the VcD, VcTD, and VcMP arms, mean number of treatment cycles (for the first four cycles) and total Vc doses (16 doses for the first four cycles) were similar: 3.8, 3.6, and 3.7 cycles and 14.5, 13 and 13.8 Vc doses, respectively. The VcD arm had the lowest rate of adverse events (AEs) grade ≥3 (58% vs 71% each in the VcTD and VcMP arms, respectively), as well as the lowest rate of discontinuations due to AEs (10% vs 18% and 16% in the VcTD and VcMP arms, respectively). The VcTD arm had the highest rate of serious AEs (50% vs 39% and 36% in the VcD and VcMP arms, respectively), as well as peripheral neuropathy (PN) of any grade (48% vs 29% and 30% in the VcD and VcMP arms, respectively). PN grade ≥3 was 6%, 12% and 13% in the VcD, VcTD, and VcMP arms, respectively. The VcTD arm had higher rates of serious embolism/thrombosis (8% vs 6% and 3%) than in the VcD and VcMP arms, respectively. All three regimens demonstrated substantial activity. The overall response rate was 60%, 70%, and 52% in the VcD, VcTD, and VcMP arms, respectively (complete response (CR)/near CR: 13%, 18% and 15%; ≥very good partial response 15%, 23% and 24%, respectively). QoL functional scores improved in all arms, except for physical, role function and global health status, which worsened in the VcTD arm only. At a preplanned IA, the three Vc-based regimens were evaluated as having similar risk/benefit considerations after four cycles. The regimens were active with well-characterized and predictable toxicities. The study continues to enroll in all three arms as recommended by the IDMC. The UPFRONT trial demonstrates the feasibility of conducting a large, randomized, outpatient, phase 3b trial in community-based oncology centers in the United States. Disclosures: Niesvizky: Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding, Speakers Bureau; Proteolix: Consultancy, Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rifkin:Millennium Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau. Gabrail:Millennium Pharmaceuticals, Inc: Research Funding. Phooshkooru:Millennium Pharmaceuticals, Inc: Consultancy, Honoraria. Charu:Millennium Pharmaceuticals, Inc: Consultancy, Honoraria, Research Funding. Corzo:Millennium Pharmaceuticals, Inc.: Employment. Neuwirth:Millennium Pharmaceuticals, Inc: Employment.

Download Full-text