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Treatment Patterns and Outcomes in Clinical Practice Among Patients with Newly-Diagnosed Multiple Myeloma: Systematic Literature Review
Abstracts apoptosis in MM cells. These preliminary results suggested that REIIBP is a HMTase and might act as an oncoprotein in t(4;14) MM cells.
PS-096 Aya-Myeloma: Real World, Single Center Experience Over Last 5 Years
PS-097 Treatment Patterns and Outcomes in Clinical Practice Among Patients with Newly-Diagnosed Multiple Myeloma: Systematic Literature Review Candice Yong,1 Huamao Mark Lin,1 Aleksandra Gara,2 Katherine Osenenko,2 Ellen Korol,2 Juliette Thompson,3 Katarina Luptakova,1 Brian Seal1
Uday Yanamandra,1 Neha Saini,2 Alka Khadwal,3 Gaurav Prakash,3 Deeepesh Lad,4 Neelam Varma,3 Subhash Varma,3 Pankaj Malhotra3
Takeda Pharmaceutical Company Ltd., Cambridge, MA; 2ICON plc.,
1
Vancouver, British Columbia; 3ICON plc., Abingdon, Oxon
PGIMER, Chandigarh, Chandigarh; 2PGIMER, India; 3PGIMER;
1
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of
4
PGIMER, Chandigarh, Chandigarh
Introduction: Multiple myeloma (MM) is considered as a disease of the old with the reported median age of 60-70 years. The disease occurs a decade earlier in the Indian subcontinent as compared to the West with a median age ranging from 45-50y in different series. It is very uncommon for MM to affect adolescents and young adult (AYA) with limited literature on the subject. Aim: The purpose of this study was to analyze the disease characteristics and outcomes of the AYA-MM in the real world setting. Patients and methods: It is a retrospective single center study conducted at a tertiary care center from North India. Records of all consecutive patients with AYAMM (15-39y of age) who were managed from 01 Jan 2010 to 31 Dec 2015 were reviewed. Survival was assessed from the date of start of treatment to the last follow-up date or death due to any cause. Results: A total of 415 patients managed for MM in the last 5 years were included in the study. The frequency of the AYA-MM was 9.6% (40/415) of whom five patients were younger than 30y. There was male preponderance with a male: female ratio of (26:14; ratio1.85). The median age of the patients was 38y (mean-36.025, 1839.9, SD e 4.67). The main presenting features were bone pain (55%), fatigue (45%), extramedullary plasmacytomas (20%) and infections (12%). The mean duration from symptom onset to diagnosis was 269d (median e 122, 15-1503, SD e 382). Organomegaly was seen in 28% (hepatomegaly in 27%, splenomegaly 12%). The performance status of the patients was good (ECOG>2 e 24%). Hypercalcemia, renal impairment (eGFR<60ml/min/ 1.73m2), anemia and lytic lesions were seen in 27.7%, 31.6%, 63.15% and 56.25% of patients respectively. 77.8% patients had abnormal k/l ratio, 61.12% patients had raised M protein and only 4 patients had Bence Jones proteinuria. Amyloid was absent in all evaluable cases except one. On risk stratification, 25%, 50%, and 75% patients were in ISS I, II and III respectively. Only 22.5% patients were transplanted (all Auto SCT), whereas most of the patients were managed with the chemotherapy even after remission induction (77.5%). The median survival after diagnosis was 388d (11-2170 days; mean - 561510d). The 3y median survival of the study population is 80.21%. Conclusion: AYA-MM patients have a higher prevalence of extramedullary disease, high-risk disease, but longer survival than that observed in series of all ages.
e54
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16th International Myeloma Workshop March 1-4, 2017
Novel agents (proteasome inhibitors [PIs], immunomodulatory agents [IMiDs]) improve disease control and survival rates in patients with newly diagnosed multiple myeloma (NDMM) compared to conventional chemotherapy. Results from clinical trials may not reflect outcomes in the real world. The objective was to summarize published data on treatment patterns and outcomes in clinical practice among patients with NDMM. Methods: A systematic literature review of observational studies of NDMM treatment patterns and clinical outcomes was conducted. Published literature was searched from Jan 2010-Jun 2016 using Medline, Embase, and PubMed databases; select conferences between 2014-2016 were also reviewed. Eligibility included studies of patients with NDMM (n50) receiving first-line treatment. Results: Included studies (n¼107) were conducted in Europe (35%), Canada or US (31%), Asia Pacific (26%), Latin America (4%), and multi-national (3%). Most studies (88%) were retrospective. Of 82 studies reporting treatment type, 95% included novel agent regimens: 82% and 83% of studies reported PI or IMiD use, respectively. The percentage of patients receiving novel agents ranged from 3% (diagnosis [dx] year 1999, US) to 83% (dx years 2009-2013, Denmark), and varied by country and patient characteristics. Proportions of patients receiving triplet regimens increased with time, likely associated with the introduction of novel agents (0% [dx years 1995-2005] - 12% [dx years 2006-2014]). Median (Mdn) treatment duration ranged from 3.4-23 months (mo), although few studies reported this (16%). Clinical outcomes (overall survival [OS], progression-free survival [PFS], overall response rate [ORR]) were reported in 92 studies. Consistently, patients receiving a PI or IMiD had longer OS than conventional chemotherapy. The minimum Mdn OS reported was 6 mo in patients with high-risk cytogenetics not treated with a PI, while 7 studies reported Mdn OS was not reached (NR, Mdn follow-up [f/u] 23-71 mo; f/u not reported in 2 studies) in patients treated with novel agents or stem cell transplant (SCT). Mdn PFS ranged from 7 mo in SCT-ineligible patients with no response to first-line novel agent treatment, to NR in patients treated with firstline PI-based triplet regimens (Mdn f/u: 23-43 mo). ORR ranged from 31% in those with high-risk cyotgenetics treated with novel agents to >90% in those receiving PI or IMiD triplet regimens or SCT. Conclusions: As targeted NDMM therapies have become
Abstracts available, treatment patterns have shifted. In this review, treatment durations were not well reported and varied substantively. Studies of novel agent regimens including PIs or IMiDs reported longer survival and higher response rates versus conventional chemotherapy, mirroring clinical trial results. Clinical outcomes were poorer in some patient subpopulations, including those with high-risk cytogenetics, indicating unmet need in these populations.
PS-098 Rates and Predictors of Stem Cell Transplant in Elderly Medicare Beneficiaries with Multiple Myeloma in the United States Candice Yong,1 Jean Yared,2 Daisuke Goto,3 Eberechukwu Onukwugha,3 Rahul Khairnar,3 Brian Seal,1 Dorothy Romanus,1 Julia Slejko3 1
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd., Cambridge, MA; 2University of Maryland School of Medicine; 3University of Maryland School of Pharmacy, Baltimore, MD
Objective: This study identified patient and contextual factors associated with the receipt of autologous stem cell transplantation (ASCT) among elderly Medicare beneficiaries with newly diagnosed symptomatic MM (NDMM). Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results registry and linked Medicare claims (SEER-Medicare) data. We identified individuals aged 66+ with an incident diagnosis of MM between 2007 and 2011, and evidence of CRAB symptoms (hypercalcemia, renal insufficiency, anemia and bone disease) based on 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 Medicare Parts A and B enrollment six months after diagnosis (individuals who died within 6 months were excluded from the study). ICD-9 and HCPCS codes were used to identify ASCT. Charlson Comorbidity Index (CCI), derived from medical claims, was used to measure comorbidity burden at the time of MM diagnosis. Baseline demographic and clinical characteristics among those who received ASCT were compared to those who did not using t-tests and Chi-square tests for continuous and categorical variables, respectively. Multivariable logistic regression was used to evaluate predictors of ASCT. Results: Among 2,698 individuals with NDMM who met our inclusion criteria, 173 (6.4%) underwent ASCT during the follow-up period. ASCT recipients were younger, more likely to be male, married, white non-Hispanic, and have fewer comorbid conditions. The rate of ASCT among recipients aged 66-69 was 22.1%, 7.2% among recipients aged 70-74, and 2.4% among those aged 75+ (p<0.001). The rate of ASCT was higher among males (7.8%) than females (5.1%) (p¼0.005). Rates of ASCT were higher among those who were non-Hispanic white (7.2%), compared to those who were non-Hispanic black (3.8%) (p¼0.004). Among those with CCI¼0, 9.2% underwent ASCT, while 7.4% of those with CCI¼1 underwent ASCT and 3.0% of those with CCI>1 underwent ASCT (p<0.001). Rates of ASCT
were higher in the Northeast (7.7%) and South (8.0%) (p¼0.04). Multivariable analysis showed that patients who were married, younger, and of white non-Hispanic race had significantly increased odds of ASCT, while those with Medicaid dual eligibility (proxy for low income), greater comorbidity burden and cardiovascular disease at baseline had significantly decreased odds of ASCT. Among the ASCT recipients, 14 (8%) died within one year of ASCT and 39 (23%) died after one year. Conclusion: ASCT is performed in fewer than 1 in 10 patients aged 66 and older. A greater proportion of ASCT recipients were non-Hispanic white, married, diagnosed at a younger age, and had a lower comorbidity burden compared to non-transplant patients. Future studies should investigate the implications of comorbidity, age and race differences on post-transplant outcomes among older MM patients.
PS-099 The Real-World Characteristics and Outcomes of Newly Diagnosed Myeloma Patients Ineligible for Clinical Trials Mark Fiala,1 James Dukeman,2 Keith Stockerl-Goldstein,2 Michael Tomasson,3 Tanya Wildes,2 Ravi Vij2 1
Washington University School of Medicine, St. Louis, MO; 2Wash-
ington University School of Medicine; 3University of Iowa Carver College of Medicine
Background: Most prospective clinical trials in Multiple Myeloma (MM) exclude patients with low performance status or impaired renal function or marrow reserve. Thus, relatively little is known about these patients. We reviewed the disease manifestation, treatment, and prognosis of these patients. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis 9 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (>1.0g/dL), UPEP (>200mg/24 hours), or SFLC (>10mg/dL); receiving a proteasome inhibitor- (PI) and/ or an immunomodulator (IMID)-based regimen a for initial MM treatment; and no prior malignancies in the past 5 years. We defined ineligibility for clinical trials as one or more of the following at time of MM diagnosis: ECOG performance status 3 or 4; creatinine >2.0mg/dL or receiving dialysis; absolute neutrophil count (ANC) <1.0x109/L or receiving growth factor support; or platelet count <50,000 x109/L or receiving platelet transfusion support. We compared the demographics, baseline presentation, and first-line treatment of these patients with the overall population using bivariate analyses. We then performed a multivariate Cox regression analysis to compare event-free survival (EFS) defined as the interval from diagnosis to disease progression or death. Results: 848 patients were available for analysis. 22% (189) met the study definition of ineligibility for clinical trials. 5% had low performance status, 15% impaired renal function, 3% impaired marrow reserve.
16th International Myeloma Workshop March 1-4, 2017
- e55
PS-096 Aya-Myeloma: Real World, Single Center Experience Over Last 5 Years
PS-097 Treatment Patterns and Outcomes in Clinical Practice Among Patients with Newly-Diagnosed Multiple Myeloma: Systematic Literature Review Candice Yong,1 Huamao Mark Lin,1 Aleksandra Gara,2 Katherine Osenenko,2 Ellen Korol,2 Juliette Thompson,3 Katarina Luptakova,1 Brian Seal1
Uday Yanamandra,1 Neha Saini,2 Alka Khadwal,3 Gaurav Prakash,3 Deeepesh Lad,4 Neelam Varma,3 Subhash Varma,3 Pankaj Malhotra3
Takeda Pharmaceutical Company Ltd., Cambridge, MA; 2ICON plc.,
1
Vancouver, British Columbia; 3ICON plc., Abingdon, Oxon
PGIMER, Chandigarh, Chandigarh; 2PGIMER, India; 3PGIMER;
1
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of
4
PGIMER, Chandigarh, Chandigarh
Introduction: Multiple myeloma (MM) is considered as a disease of the old with the reported median age of 60-70 years. The disease occurs a decade earlier in the Indian subcontinent as compared to the West with a median age ranging from 45-50y in different series. It is very uncommon for MM to affect adolescents and young adult (AYA) with limited literature on the subject. Aim: The purpose of this study was to analyze the disease characteristics and outcomes of the AYA-MM in the real world setting. Patients and methods: It is a retrospective single center study conducted at a tertiary care center from North India. Records of all consecutive patients with AYAMM (15-39y of age) who were managed from 01 Jan 2010 to 31 Dec 2015 were reviewed. Survival was assessed from the date of start of treatment to the last follow-up date or death due to any cause. Results: A total of 415 patients managed for MM in the last 5 years were included in the study. The frequency of the AYA-MM was 9.6% (40/415) of whom five patients were younger than 30y. There was male preponderance with a male: female ratio of (26:14; ratio1.85). The median age of the patients was 38y (mean-36.025, 1839.9, SD e 4.67). The main presenting features were bone pain (55%), fatigue (45%), extramedullary plasmacytomas (20%) and infections (12%). The mean duration from symptom onset to diagnosis was 269d (median e 122, 15-1503, SD e 382). Organomegaly was seen in 28% (hepatomegaly in 27%, splenomegaly 12%). The performance status of the patients was good (ECOG>2 e 24%). Hypercalcemia, renal impairment (eGFR<60ml/min/ 1.73m2), anemia and lytic lesions were seen in 27.7%, 31.6%, 63.15% and 56.25% of patients respectively. 77.8% patients had abnormal k/l ratio, 61.12% patients had raised M protein and only 4 patients had Bence Jones proteinuria. Amyloid was absent in all evaluable cases except one. On risk stratification, 25%, 50%, and 75% patients were in ISS I, II and III respectively. Only 22.5% patients were transplanted (all Auto SCT), whereas most of the patients were managed with the chemotherapy even after remission induction (77.5%). The median survival after diagnosis was 388d (11-2170 days; mean - 561510d). The 3y median survival of the study population is 80.21%. Conclusion: AYA-MM patients have a higher prevalence of extramedullary disease, high-risk disease, but longer survival than that observed in series of all ages.
e54
-
16th International Myeloma Workshop March 1-4, 2017
Novel agents (proteasome inhibitors [PIs], immunomodulatory agents [IMiDs]) improve disease control and survival rates in patients with newly diagnosed multiple myeloma (NDMM) compared to conventional chemotherapy. Results from clinical trials may not reflect outcomes in the real world. The objective was to summarize published data on treatment patterns and outcomes in clinical practice among patients with NDMM. Methods: A systematic literature review of observational studies of NDMM treatment patterns and clinical outcomes was conducted. Published literature was searched from Jan 2010-Jun 2016 using Medline, Embase, and PubMed databases; select conferences between 2014-2016 were also reviewed. Eligibility included studies of patients with NDMM (n50) receiving first-line treatment. Results: Included studies (n¼107) were conducted in Europe (35%), Canada or US (31%), Asia Pacific (26%), Latin America (4%), and multi-national (3%). Most studies (88%) were retrospective. Of 82 studies reporting treatment type, 95% included novel agent regimens: 82% and 83% of studies reported PI or IMiD use, respectively. The percentage of patients receiving novel agents ranged from 3% (diagnosis [dx] year 1999, US) to 83% (dx years 2009-2013, Denmark), and varied by country and patient characteristics. Proportions of patients receiving triplet regimens increased with time, likely associated with the introduction of novel agents (0% [dx years 1995-2005] - 12% [dx years 2006-2014]). Median (Mdn) treatment duration ranged from 3.4-23 months (mo), although few studies reported this (16%). Clinical outcomes (overall survival [OS], progression-free survival [PFS], overall response rate [ORR]) were reported in 92 studies. Consistently, patients receiving a PI or IMiD had longer OS than conventional chemotherapy. The minimum Mdn OS reported was 6 mo in patients with high-risk cytogenetics not treated with a PI, while 7 studies reported Mdn OS was not reached (NR, Mdn follow-up [f/u] 23-71 mo; f/u not reported in 2 studies) in patients treated with novel agents or stem cell transplant (SCT). Mdn PFS ranged from 7 mo in SCT-ineligible patients with no response to first-line novel agent treatment, to NR in patients treated with firstline PI-based triplet regimens (Mdn f/u: 23-43 mo). ORR ranged from 31% in those with high-risk cyotgenetics treated with novel agents to >90% in those receiving PI or IMiD triplet regimens or SCT. Conclusions: As targeted NDMM therapies have become
Abstracts available, treatment patterns have shifted. In this review, treatment durations were not well reported and varied substantively. Studies of novel agent regimens including PIs or IMiDs reported longer survival and higher response rates versus conventional chemotherapy, mirroring clinical trial results. Clinical outcomes were poorer in some patient subpopulations, including those with high-risk cytogenetics, indicating unmet need in these populations.
PS-098 Rates and Predictors of Stem Cell Transplant in Elderly Medicare Beneficiaries with Multiple Myeloma in the United States Candice Yong,1 Jean Yared,2 Daisuke Goto,3 Eberechukwu Onukwugha,3 Rahul Khairnar,3 Brian Seal,1 Dorothy Romanus,1 Julia Slejko3 1
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd., Cambridge, MA; 2University of Maryland School of Medicine; 3University of Maryland School of Pharmacy, Baltimore, MD
Objective: This study identified patient and contextual factors associated with the receipt of autologous stem cell transplantation (ASCT) among elderly Medicare beneficiaries with newly diagnosed symptomatic MM (NDMM). Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results registry and linked Medicare claims (SEER-Medicare) data. We identified individuals aged 66+ with an incident diagnosis of MM between 2007 and 2011, and evidence of CRAB symptoms (hypercalcemia, renal insufficiency, anemia and bone disease) based on 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 Medicare Parts A and B enrollment six months after diagnosis (individuals who died within 6 months were excluded from the study). ICD-9 and HCPCS codes were used to identify ASCT. Charlson Comorbidity Index (CCI), derived from medical claims, was used to measure comorbidity burden at the time of MM diagnosis. Baseline demographic and clinical characteristics among those who received ASCT were compared to those who did not using t-tests and Chi-square tests for continuous and categorical variables, respectively. Multivariable logistic regression was used to evaluate predictors of ASCT. Results: Among 2,698 individuals with NDMM who met our inclusion criteria, 173 (6.4%) underwent ASCT during the follow-up period. ASCT recipients were younger, more likely to be male, married, white non-Hispanic, and have fewer comorbid conditions. The rate of ASCT among recipients aged 66-69 was 22.1%, 7.2% among recipients aged 70-74, and 2.4% among those aged 75+ (p<0.001). The rate of ASCT was higher among males (7.8%) than females (5.1%) (p¼0.005). Rates of ASCT were higher among those who were non-Hispanic white (7.2%), compared to those who were non-Hispanic black (3.8%) (p¼0.004). Among those with CCI¼0, 9.2% underwent ASCT, while 7.4% of those with CCI¼1 underwent ASCT and 3.0% of those with CCI>1 underwent ASCT (p<0.001). Rates of ASCT
were higher in the Northeast (7.7%) and South (8.0%) (p¼0.04). Multivariable analysis showed that patients who were married, younger, and of white non-Hispanic race had significantly increased odds of ASCT, while those with Medicaid dual eligibility (proxy for low income), greater comorbidity burden and cardiovascular disease at baseline had significantly decreased odds of ASCT. Among the ASCT recipients, 14 (8%) died within one year of ASCT and 39 (23%) died after one year. Conclusion: ASCT is performed in fewer than 1 in 10 patients aged 66 and older. A greater proportion of ASCT recipients were non-Hispanic white, married, diagnosed at a younger age, and had a lower comorbidity burden compared to non-transplant patients. Future studies should investigate the implications of comorbidity, age and race differences on post-transplant outcomes among older MM patients.
PS-099 The Real-World Characteristics and Outcomes of Newly Diagnosed Myeloma Patients Ineligible for Clinical Trials Mark Fiala,1 James Dukeman,2 Keith Stockerl-Goldstein,2 Michael Tomasson,3 Tanya Wildes,2 Ravi Vij2 1
Washington University School of Medicine, St. Louis, MO; 2Wash-
ington University School of Medicine; 3University of Iowa Carver College of Medicine
Background: Most prospective clinical trials in Multiple Myeloma (MM) exclude patients with low performance status or impaired renal function or marrow reserve. Thus, relatively little is known about these patients. We reviewed the disease manifestation, treatment, and prognosis of these patients. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis 9 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (>1.0g/dL), UPEP (>200mg/24 hours), or SFLC (>10mg/dL); receiving a proteasome inhibitor- (PI) and/ or an immunomodulator (IMID)-based regimen a for initial MM treatment; and no prior malignancies in the past 5 years. We defined ineligibility for clinical trials as one or more of the following at time of MM diagnosis: ECOG performance status 3 or 4; creatinine >2.0mg/dL or receiving dialysis; absolute neutrophil count (ANC) <1.0x109/L or receiving growth factor support; or platelet count <50,000 x109/L or receiving platelet transfusion support. We compared the demographics, baseline presentation, and first-line treatment of these patients with the overall population using bivariate analyses. We then performed a multivariate Cox regression analysis to compare event-free survival (EFS) defined as the interval from diagnosis to disease progression or death. Results: 848 patients were available for analysis. 22% (189) met the study definition of ineligibility for clinical trials. 5% had low performance status, 15% impaired renal function, 3% impaired marrow reserve.
16th International Myeloma Workshop March 1-4, 2017
- e55