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Treatment Patterns From 2009-2015 in Patients With Newly Diagnosed Multiple Myeloma in the United States: A Report From the Connect® MM Registry
Abstracts -27% (range, 4%-58%) vs sM-Pro -6% (range -57%-15%) in the first week for all pts who responded to therapy (n¼18) and -3% (range -69%-64%) vs sM-Pro +3% (range -24%-34%) for nonresponders (n¼24). Among pts who achieved SD during C1, mid cycle changes in the levels of sBCMA resulting in >30% increases relative to the sample obtained one week prior (n¼5) correctly predicted disease progression during subsequent cycles. Conclusions: We have shown that sBCMA levels change more quickly than conventional sM Pro levels and more reliably than sFLC levels among MM pts receiving any new treatment. Specifically, changes in sBCMA levels >30% predict disease progression. Thus, frequent assessment of serum BCMA levels during the first cycle of any new treatment may be helpful to make more rapid decisions determining the efficacy of a new MM therapy.
OP-033 Natural History of t(11;14) Multiple Myeloma Arjun Lakshman,1 Muhammed Alhaj Moustafa,2 S.Vincent Rajkumar,3 Angela Dispenzieri,2 Morie A. Gertz,4 Francis Buadi,5 Martha Lacy,4 David Dingli,6 Amie Fonder,5 Suzanne Hayman,5 Miriam Hobbs,5 Wilson Gonsalves,5 Yi Lisa Hwa,3 Prashant Kapoor,6 Robert Kyle,5 Nelson Leung,3 Ronald Go,3 John Lust,3 Stephen Russell,3 Steven Zeldenrust,3 Shaji Kumar4 1
Division of Hematology, Mayo Clinic, Rochester, MN; 2Mayo Clinic;
3
Mayo Clinic, Rochester, Mn; 4Mayo Clinic, Rochester, MN; 5Mayo 6
Clinic, Rochester, MN; Mayo Clinic, Rochester, MN
Introduction: Presence of t(11;14) in interphase fluorescent insitu hybridization (iFISH) on bone marrow plasma cells is seen in about 15% patients of multiple myeloma (MM) at diagnosis. t(11;14) is regarded as a standard risk cytogenetic marker for prognosis in MM. We examined the long term outcomes of MM with t(11;14) seen at our institution between 2004 and 2014. Methods: We retrospectively identified 366 patients with MM who had t(11;14) demonstrable in bone marrow samples by iFISH done before or within one year of starting treatment for MM. Their clinical records were reviewed and outcomes analyzed with respect to time to first progression or death (PFS1), time to second progression or death in patients receiving second line therapy (PFS2) and overall survival (OS). The study was approved by institutional review board. Results: The median age at diagnosis was 63.7 years (range, 22.1-95.4) with 64.5% of patients being male. Eighty nine (24.3%) patients were above 70 years of age at diagnosis. Bone disease at diagnosis was present in 70.5% patients. 33.8%, 40.3% and 25.9% patients belonged to ISS 1, II and III stages respectively. 13% patients had elevated LDH. mSMART high risk cytogenetic abnormalities (del 17p or monosomy 17) were identified in 10.6% patients. The median follow up period was 3.8 years (95% CI, 0.59.8and 209 (57.1%) patients were alive at last follow-up. Among patients receiving proteasome inhibitor (PI)-based, immunomodulator (IMiD)-based, PI+IMiD based or other agent based induction
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16th International Myeloma Workshop, March 1-4, 2017
therapy, 71.2%, 70.3%, 90.4% and 37.5% patients respectively attained PR as best response to induction (p<0.0001). During their course, 223 (60.9%) patients underwent stem cell transplant. Median PFS1, PFS2 and OS were 2.0 (95% CI, 1.8-2.3,), 4.0 (95% CI, 3.3-4.4,) and 6.5 (95% CI, 5.5-8.8,) years respectively. At 5 and 10 years from diagnosis, estimated 59.5% and 32.3% patients were surviving respectively. In a Cox-proportional hazards model with age >70 years, male gender, induction therapy type (novel agent-based vs others), presence of high risk cytogenetics, and ISS stage as baseline predictor variables, age>70 years [HR-2.27 (95% CI¼1.55-3.29) and p<0.0001], high risk cytogenetics [HR-2.38 (95% CI¼1.43-2.95) and p¼0.0012], ISS III vs ISS II [HR-1.80 (95%CI¼1.11-2.95) and p¼0.0168]and ISS II vs ISS I [HR-1.71 (95%CI¼1.10-2.71) and p¼0.0162] were associated with reduced survival. There was no difference in OS between those patients who started treatment before, or in 2010 and later. Conclusion: Our study characterizes the outcomes of a large cohort of MM patients with t(11;14) at diagnosis. Advanced age, high risk cytogenetic abnormalities and advanced stage at diagnosis were associated with worse OS.
OP-034 Treatment Patterns From 2009-2015 in Patients With Newly Diagnosed Multiple Myeloma in the United States: A Report From the ConnectÒ MM Registry Robert Rifkin,1 Rafat Abonour,2 Brian Durie,3 Cristina Gasparetto,4 Sundar Jagannath,5 Mohit Narang,6 Jatin Shah,7 Howard Terebelo,8 Kathleen Toomey,9 Amani Kitali,10 Faiza Zafar,10 Shankar Srinivasan,11 James Hardin12 1
US Oncology Research/ Rocky Mountain Cancer Centers, Denver,
CO; 2Indiana University Simon Cancer Center, Indianapolis, IN; 3Cedars-Sinai Medical Center, Los Angeles, CA; 4Duke University, Hematologic Malignancies & Cellular Therapy, Durham, NC; 5Mount Sinai Hospital, New York, NY; 6US Oncology Research, Maryland Oncology Hematology, Columbia, MD; 7MD Anderson Cancer Center, Houston, TX; 8Providence Cancer Institute, Southfield, MI; 9
Steeplechase Cancer Center, Somerville, NJ;
tion, Summit, NJ;
10
Celgene Corpora-
11
Celgene Corporation, Summit, NJ; 12University of
South Carolina, Columbia, SC
Introduction: From 2009-2015, use of novel therapies (immunomodulators and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time may help project near-term future treatment patterns. ConnectÒ MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed (ND) MM. Study sites represented all census regions, allowing a reasonable generalizability to patterns for the US. Methods: Enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493
Abstracts NDMM pts from Sep 2009 to Dec 2011; Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at baseline and quarterly visits until death or discontinuation. This analysis was conducted for all treated pts (N¼2848) as of May 2016. Choice of first-line, maintenance, and second-line treatment was analyzed in 6-month intervals. Trends will be visually represented in a novel way (“Tepee” plots). Results: Median (range) follow-up for all pts was 39.3 mo (0.03-78.4 mo) in Cohort 1 and 15.4 mo (0.2-40.1 mo) in Cohort 2. For treated pts, the median age was 67 y (range, 24-94 y), 58% were male, 83% were white, and 38% of those reporting ISS stage had stage III MM. By US region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 84%) were from community sites; 397 (13.9%) were from academic sites, and the rest from government sites. A total of 1805 (63.4%) were aged 70 y and 1043 (36.6%) were aged >70 y; 666 (23.4%) have progressed and entered second-line treatment. The 4 most common induction regimens for pts aged 70 y, in decreasing frequency, were lenalidomide (R), bortezomib (V), and dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 4 most common induction regimens for pts aged >70 y were VD, RD, RVD, and CyBorD. Triplet therapy in first-line induction increased in use from 2009 to 2014. The 4 most frequent maintenance regimens for stem cell transplant (SCT) recipients (n¼553) were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for non-SCT pts (n¼547) were R monotherapy, RD, V monotherapy, and VD. The most prevalent regimens in the second line were VD, RD, V, and RVD. Conclusions: Our work characterized induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional, registry study in the US. Use of triplet therapy increased in the time period; RVD was the most frequently used triplet for all pts. The most common maintenance regimens included R as monotherapy or in combination.
2180/1577, subtype IgG 2028 (54%), IgA 714 (19%), IgM 21 (0.6%), lines of induction regimens prior to HSCT one in 2003 pts (53%), two in 724 pts ( 19.3%), > 2 in 348 pts (9.3%), and missing in 682 pts (18%). Induction regimens included IMIDs and proteasome inhibitor (PI)s with alkylating agents in 1266 pts (33.7%), IMIDs and PIs with no alkylating agents in 1328 (35.5%), and alkylating agents with no IMIDs or PIs in 478 (12.7%) and missing data in 685 (18%). Radiotherapy was used pre HSCT in 614 pts (16.3%), no radiation in 2461 pts (66%) and missing data in 682 (18.2%). Plerixafor (P) was administered mostly for poor HSC mobilization as defined by the centers in 285 pts (7.6%), 3373 pts (90%) did not get plerixafor, and data are missing in 99 pts (2.6%). Disease status at HSCT; CR/VGPR in 1664 pts (44.3%), PR in 1721 (46%), 12 mo 799 pts (21%). Conditioning regimen was mainly melphalan in 3659 pts (97.4%), and melphalan with other drugs in 75 pts (2.0%). KARNOFSKY PERFORMANCE STATUS >90% was documented in 2326 pts (62%) and <90 % in 1086 pts(29%). Number of HSC collected <3x 10 6 in 239 pts (6.4%), 3-5 in 397 pts ( 10.6%), > 5x 10 6 in 1394 pts (37%), and data missing in 1727 (46%). The number of CD 34+ HSC infused <3x 106 in 760 pts (20%), 3-5x 10 6 in 1055 pts (28%0, >5 x 10 6in 799 pts (21%), and missing in 1143 (30%). Results: A total of 141 pts developed SPM with cumulative incidence of 5.4% (95%CI 4.4,6.3) at 72 mo. Data are missing in 414 pts (11%). Median time to development of SPM is 33 mo. (2.186.5) with 75% occurring in the first 50 mo. Ninety nine pts developed solid tumors and 31 hematologic malignancies and unknown type in 11. Overall survival for the whole group is 65.4% (63-67) at 5 yr post auto transplant, and 38% (25-52%) at 5 yr post-SPM in pts who developed SPM. Use of radiotherapy, type of induction, HSC cell dose did not influence the cumulative incidence of SPM. Conclusion: The incidence of SPM in this large prospective study is 5.4% at 72 months and is comparable to the reported incidence of SPM in the literature. Disclosure of Interest: F. Sahebi, none declared, S. Iacobelli, none declared, L. Koster none declared L. Gardaret none declared, N. Kroger received research fund from Sanofi , Curly Morris, none declared.
OP-035 Incidence of Secondary Primary Malignancies (SPM) in Patients With Multiple Myeloma (CALM Study) 1
Firoozeh Sahebi 1
City of Hope Medical Center -Kaiser so. California Medical Group,
Duarte, CA
Introduction: As the outcome of multiple myeloma (MM) patients (pts) continues to improve, development of late complications particularly SPM are of concerns. We examined the incidence of SPM in MM pts who were enrolled in the prospective EBMT CALM study (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma). Marterial and methods: A total of 3757 pts with MM were enrolled and underwent first autologous hematopoietic stem cell transplant (HSCT). Pts characteristics are as follows: median age 59 y/o (19-77), gender M/F
OP-036 Clinical Profiles and Outcomes in 1203 Newly Diagnosed Patients With Systemic AL Amyloidosis e First Analysis of the ALChemy Study. Richa Manwani,1 Darren Foard,2 Shameem Mahmood,3 Sajitha Sachchithanantham,2 Marianna Fontana,3 Carol Whelan,3 Thirusha Lane,4 Helen Lachmann,3 Julian Gillmore,3 Philip Hawkins,3 Cristina Quarta,3 Taryn Youngstein,4 Tamer Rezk,4 Ashutosh Wechalekar3 1
National Amyloidosis Centre, UCL (Royal Free Campus), London,
London, United Kingdom; 2UCL; 3National Amyloidosis Centre, UCL (Royal Free Campus), United Kingdom; 4National Amyloidosis Centre, UCL (Royal Free Campus), United Kingdom
16th International Myeloma Workshop, March 1-4, 2017
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OP-033 Natural History of t(11;14) Multiple Myeloma Arjun Lakshman,1 Muhammed Alhaj Moustafa,2 S.Vincent Rajkumar,3 Angela Dispenzieri,2 Morie A. Gertz,4 Francis Buadi,5 Martha Lacy,4 David Dingli,6 Amie Fonder,5 Suzanne Hayman,5 Miriam Hobbs,5 Wilson Gonsalves,5 Yi Lisa Hwa,3 Prashant Kapoor,6 Robert Kyle,5 Nelson Leung,3 Ronald Go,3 John Lust,3 Stephen Russell,3 Steven Zeldenrust,3 Shaji Kumar4 1
Division of Hematology, Mayo Clinic, Rochester, MN; 2Mayo Clinic;
3
Mayo Clinic, Rochester, Mn; 4Mayo Clinic, Rochester, MN; 5Mayo 6
Clinic, Rochester, MN; Mayo Clinic, Rochester, MN
Introduction: Presence of t(11;14) in interphase fluorescent insitu hybridization (iFISH) on bone marrow plasma cells is seen in about 15% patients of multiple myeloma (MM) at diagnosis. t(11;14) is regarded as a standard risk cytogenetic marker for prognosis in MM. We examined the long term outcomes of MM with t(11;14) seen at our institution between 2004 and 2014. Methods: We retrospectively identified 366 patients with MM who had t(11;14) demonstrable in bone marrow samples by iFISH done before or within one year of starting treatment for MM. Their clinical records were reviewed and outcomes analyzed with respect to time to first progression or death (PFS1), time to second progression or death in patients receiving second line therapy (PFS2) and overall survival (OS). The study was approved by institutional review board. Results: The median age at diagnosis was 63.7 years (range, 22.1-95.4) with 64.5% of patients being male. Eighty nine (24.3%) patients were above 70 years of age at diagnosis. Bone disease at diagnosis was present in 70.5% patients. 33.8%, 40.3% and 25.9% patients belonged to ISS 1, II and III stages respectively. 13% patients had elevated LDH. mSMART high risk cytogenetic abnormalities (del 17p or monosomy 17) were identified in 10.6% patients. The median follow up period was 3.8 years (95% CI, 0.59.8and 209 (57.1%) patients were alive at last follow-up. Among patients receiving proteasome inhibitor (PI)-based, immunomodulator (IMiD)-based, PI+IMiD based or other agent based induction
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therapy, 71.2%, 70.3%, 90.4% and 37.5% patients respectively attained PR as best response to induction (p<0.0001). During their course, 223 (60.9%) patients underwent stem cell transplant. Median PFS1, PFS2 and OS were 2.0 (95% CI, 1.8-2.3,), 4.0 (95% CI, 3.3-4.4,) and 6.5 (95% CI, 5.5-8.8,) years respectively. At 5 and 10 years from diagnosis, estimated 59.5% and 32.3% patients were surviving respectively. In a Cox-proportional hazards model with age >70 years, male gender, induction therapy type (novel agent-based vs others), presence of high risk cytogenetics, and ISS stage as baseline predictor variables, age>70 years [HR-2.27 (95% CI¼1.55-3.29) and p<0.0001], high risk cytogenetics [HR-2.38 (95% CI¼1.43-2.95) and p¼0.0012], ISS III vs ISS II [HR-1.80 (95%CI¼1.11-2.95) and p¼0.0168]and ISS II vs ISS I [HR-1.71 (95%CI¼1.10-2.71) and p¼0.0162] were associated with reduced survival. There was no difference in OS between those patients who started treatment before, or in 2010 and later. Conclusion: Our study characterizes the outcomes of a large cohort of MM patients with t(11;14) at diagnosis. Advanced age, high risk cytogenetic abnormalities and advanced stage at diagnosis were associated with worse OS.
OP-034 Treatment Patterns From 2009-2015 in Patients With Newly Diagnosed Multiple Myeloma in the United States: A Report From the ConnectÒ MM Registry Robert Rifkin,1 Rafat Abonour,2 Brian Durie,3 Cristina Gasparetto,4 Sundar Jagannath,5 Mohit Narang,6 Jatin Shah,7 Howard Terebelo,8 Kathleen Toomey,9 Amani Kitali,10 Faiza Zafar,10 Shankar Srinivasan,11 James Hardin12 1
US Oncology Research/ Rocky Mountain Cancer Centers, Denver,
CO; 2Indiana University Simon Cancer Center, Indianapolis, IN; 3Cedars-Sinai Medical Center, Los Angeles, CA; 4Duke University, Hematologic Malignancies & Cellular Therapy, Durham, NC; 5Mount Sinai Hospital, New York, NY; 6US Oncology Research, Maryland Oncology Hematology, Columbia, MD; 7MD Anderson Cancer Center, Houston, TX; 8Providence Cancer Institute, Southfield, MI; 9
Steeplechase Cancer Center, Somerville, NJ;
tion, Summit, NJ;
10
Celgene Corpora-
11
Celgene Corporation, Summit, NJ; 12University of
South Carolina, Columbia, SC
Introduction: From 2009-2015, use of novel therapies (immunomodulators and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time may help project near-term future treatment patterns. ConnectÒ MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed (ND) MM. Study sites represented all census regions, allowing a reasonable generalizability to patterns for the US. Methods: Enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493
Abstracts NDMM pts from Sep 2009 to Dec 2011; Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at baseline and quarterly visits until death or discontinuation. This analysis was conducted for all treated pts (N¼2848) as of May 2016. Choice of first-line, maintenance, and second-line treatment was analyzed in 6-month intervals. Trends will be visually represented in a novel way (“Tepee” plots). Results: Median (range) follow-up for all pts was 39.3 mo (0.03-78.4 mo) in Cohort 1 and 15.4 mo (0.2-40.1 mo) in Cohort 2. For treated pts, the median age was 67 y (range, 24-94 y), 58% were male, 83% were white, and 38% of those reporting ISS stage had stage III MM. By US region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 84%) were from community sites; 397 (13.9%) were from academic sites, and the rest from government sites. A total of 1805 (63.4%) were aged 70 y and 1043 (36.6%) were aged >70 y; 666 (23.4%) have progressed and entered second-line treatment. The 4 most common induction regimens for pts aged 70 y, in decreasing frequency, were lenalidomide (R), bortezomib (V), and dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 4 most common induction regimens for pts aged >70 y were VD, RD, RVD, and CyBorD. Triplet therapy in first-line induction increased in use from 2009 to 2014. The 4 most frequent maintenance regimens for stem cell transplant (SCT) recipients (n¼553) were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for non-SCT pts (n¼547) were R monotherapy, RD, V monotherapy, and VD. The most prevalent regimens in the second line were VD, RD, V, and RVD. Conclusions: Our work characterized induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional, registry study in the US. Use of triplet therapy increased in the time period; RVD was the most frequently used triplet for all pts. The most common maintenance regimens included R as monotherapy or in combination.
2180/1577, subtype IgG 2028 (54%), IgA 714 (19%), IgM 21 (0.6%), lines of induction regimens prior to HSCT one in 2003 pts (53%), two in 724 pts ( 19.3%), > 2 in 348 pts (9.3%), and missing in 682 pts (18%). Induction regimens included IMIDs and proteasome inhibitor (PI)s with alkylating agents in 1266 pts (33.7%), IMIDs and PIs with no alkylating agents in 1328 (35.5%), and alkylating agents with no IMIDs or PIs in 478 (12.7%) and missing data in 685 (18%). Radiotherapy was used pre HSCT in 614 pts (16.3%), no radiation in 2461 pts (66%) and missing data in 682 (18.2%). Plerixafor (P) was administered mostly for poor HSC mobilization as defined by the centers in 285 pts (7.6%), 3373 pts (90%) did not get plerixafor, and data are missing in 99 pts (2.6%). Disease status at HSCT; CR/VGPR in 1664 pts (44.3%), PR in 1721 (46%), 12 mo 799 pts (21%). Conditioning regimen was mainly melphalan in 3659 pts (97.4%), and melphalan with other drugs in 75 pts (2.0%). KARNOFSKY PERFORMANCE STATUS >90% was documented in 2326 pts (62%) and <90 % in 1086 pts(29%). Number of HSC collected <3x 10 6 in 239 pts (6.4%), 3-5 in 397 pts ( 10.6%), > 5x 10 6 in 1394 pts (37%), and data missing in 1727 (46%). The number of CD 34+ HSC infused <3x 106 in 760 pts (20%), 3-5x 10 6 in 1055 pts (28%0, >5 x 10 6in 799 pts (21%), and missing in 1143 (30%). Results: A total of 141 pts developed SPM with cumulative incidence of 5.4% (95%CI 4.4,6.3) at 72 mo. Data are missing in 414 pts (11%). Median time to development of SPM is 33 mo. (2.186.5) with 75% occurring in the first 50 mo. Ninety nine pts developed solid tumors and 31 hematologic malignancies and unknown type in 11. Overall survival for the whole group is 65.4% (63-67) at 5 yr post auto transplant, and 38% (25-52%) at 5 yr post-SPM in pts who developed SPM. Use of radiotherapy, type of induction, HSC cell dose did not influence the cumulative incidence of SPM. Conclusion: The incidence of SPM in this large prospective study is 5.4% at 72 months and is comparable to the reported incidence of SPM in the literature. Disclosure of Interest: F. Sahebi, none declared, S. Iacobelli, none declared, L. Koster none declared L. Gardaret none declared, N. Kroger received research fund from Sanofi , Curly Morris, none declared.
OP-035 Incidence of Secondary Primary Malignancies (SPM) in Patients With Multiple Myeloma (CALM Study) 1
Firoozeh Sahebi 1
City of Hope Medical Center -Kaiser so. California Medical Group,
Duarte, CA
Introduction: As the outcome of multiple myeloma (MM) patients (pts) continues to improve, development of late complications particularly SPM are of concerns. We examined the incidence of SPM in MM pts who were enrolled in the prospective EBMT CALM study (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma). Marterial and methods: A total of 3757 pts with MM were enrolled and underwent first autologous hematopoietic stem cell transplant (HSCT). Pts characteristics are as follows: median age 59 y/o (19-77), gender M/F
OP-036 Clinical Profiles and Outcomes in 1203 Newly Diagnosed Patients With Systemic AL Amyloidosis e First Analysis of the ALChemy Study. Richa Manwani,1 Darren Foard,2 Shameem Mahmood,3 Sajitha Sachchithanantham,2 Marianna Fontana,3 Carol Whelan,3 Thirusha Lane,4 Helen Lachmann,3 Julian Gillmore,3 Philip Hawkins,3 Cristina Quarta,3 Taryn Youngstein,4 Tamer Rezk,4 Ashutosh Wechalekar3 1
National Amyloidosis Centre, UCL (Royal Free Campus), London,
London, United Kingdom; 2UCL; 3National Amyloidosis Centre, UCL (Royal Free Campus), United Kingdom; 4National Amyloidosis Centre, UCL (Royal Free Campus), United Kingdom
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