Race and Outcomes of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Blacks are twice as likely to develop and die from multiple myeloma (MM), and are less likely to receive an autologous hematopoietic-cell transplant (AHCT) for MM compared to Whites. The influence of race on outcomes of AHCT for MM is not well described. We compared the probability of overall survival (OS), progression-free survival (PFS), disease progression, and nonrelapse mortality (NRM) among Black (N=303) and White (N=1892) recipients of AHCT for MM, who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The Black cohort was more likely to be female, and had better Karnofsky performance scores, but lower hemoglobin and albumin levels at diagnosis. Black recipients were younger and more likely to be transplanted later in their disease course. Disease stage and treatment characteristics prior to AHCT were similar between the 2 groups. Black and White recipients had similar probabilities of 5-year OS (52% versus 47%, P=.19) and PFS (19% versus 21%, P=.64) as well as cumulative incidences of disease progression (72% versus 72%, P=.97) and NRM (9% versus 8%, P=.52). In multivariate analyses, race was not associated with any of these endpoints. Black recipients of AHCT for MM have similar outcomes compared to Whites, suggesting that the reasons underlying lower rates of AHCT in Blacks need to be studied further to ensure equal access to effective therapy. Blacks are twice as likely to develop and die from multiple myeloma (MM), and are less likely to receive an autologous hematopoietic-cell transplant (AHCT) for MM compared to Whites. The influence of race on outcomes of AHCT for MM is not well described. We compared the probability of overall survival (OS), progression-free survival (PFS), disease progression, and nonrelapse mortality (NRM) among Black (N=303) and White (N=1892) recipients of AHCT for MM, who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The Black cohort was more likely to be female, and had better Karnofsky performance scores, but lower hemoglobin and albumin levels at diagnosis. Black recipients were younger and more likely to be transplanted later in their disease course. Disease stage and treatment characteristics prior to AHCT were similar between the 2 groups. Black and White recipients had similar probabilities of 5-year OS (52% versus 47%, P=.19) and PFS (19% versus 21%, P=.64) as well as cumulative incidences of disease progression (72% versus 72%, P=.97) and NRM (9% versus 8%, P=.52). In multivariate analyses, race was not associated with any of these endpoints. Black recipients of AHCT for MM have similar outcomes compared to Whites, suggesting that the reasons underlying lower rates of AHCT in Blacks need to be studied further to ensure equal access to effective therapy. Multiple myeloma (MM) remains an incurable disease, although prognosis has improved in the past decade [1Kyle R.A. Rajkumar S.V. Epidemiology of the plasma-cell disorders.Best Pract Res Clin Haematol. 2007; 20: 637-664Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 2Kumar S.K. Rajkumar S.V. Dispenzieri A. et al.Improved survival in multiple myeloma and the impact of novel therapies.Blood. 2008; 111: 2516-2520Crossref PubMed Scopus (1805) Google Scholar]. It is the most common hematologic malignancy among Blacks, and is the only hematologic malignancy that is more frequent in this racial group compared with Whites. In the United States, MM and its precursor disease monoclonal gammopathy of undetermined significance (MGUS) are twice as common in Blacks (annual incidence of 14.4/100,000 in men and 9.8/100,000 in women compared with 6.6/100,000 in White men and 4.1/100,000 in White women) [1Kyle R.A. Rajkumar S.V. Epidemiology of the plasma-cell disorders.Best Pract Res Clin Haematol. 2007; 20: 637-664Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar, 3Brown L.M. Gridley G. Check D. Landgren O. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders.Blood. 2008; 111: 3388-3394Crossref PubMed Scopus (153) Google Scholar, 4Landgren O. Gridley G. Turesson I. et al.Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among black and white veterans in the United States.Blood. 2006; 107: 904-906Crossref PubMed Scopus (244) Google Scholar, 5Ries L, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2005, based on November 2007 SEER data submission, posted to the SEER web site, 2008. last accessed January 2009.Google Scholar, 6Singh J. Dudley Jr., A.W. Kulig K.A. Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting.J Lab Clin Med. 1990; 116: 785-789PubMed Google Scholar, 7Landgren O. Katzmann J.A. Hsing A.W. et al.Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana.Mayo Clin Proc. 2007; 82: 1468-1473Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]. Proposed factors to explain the increased incidence among Blacks include socioeconomic factors, greater exposure to hazardous materials, genetic predisposition, greater degree of background antigenic stimulation, and a greater prevalence of obesity [8Samanic C. Gridley G. Chow W.H. Lubin J. Hoover R.N. Fraumeni Jr., J.F. Obesity and cancer risk among white and black United States veterans.Cancer Causes Control. 2004; 15: 35-43Crossref PubMed Scopus (263) Google Scholar, 9Benjamin M. Reddy S. Brawley O.W. Myeloma and race: a review of the literature.Cancer Metastasis Rev. 2003; 22: 87-93Crossref PubMed Scopus (73) Google Scholar, 10Friedman G.D. Herrinton L.J. Obesity and multiple myeloma.Cancer Causes Control. 1994; 5: 479-483Crossref PubMed Scopus (48) Google Scholar]. Mortality rates from MM in the United States are twice as high for Blacks compared to Whites (8.3/100,000 for men and 6.0/100,000 for women compared to 4.3/100,000 and 2.8/100,000 for White men and women, respectively) [11http://seer.cancer.gov/statfacts/html/mulmy.html. last accessed January 2009.Google Scholar]. Socioeconomic factors that may have an impact on access to cancer therapy and therapeutic choices include place of residence, distance from care centers, unemployment, availability and quality of health insurance, poor nutrition, exposure to infectious agents, lower educational level, and annual income [12Abou-Jawde R.M. Baz R. Walker E. et al.The role of race, socioeconomic status, and distance traveled on the outcome of black patients with multiple myeloma.Haematologica. 2006; 91: 1410-1413PubMed Google Scholar, 13Savage D. Lindenbaum J. Van Ryzin J. Struening E. Garrett T.J. Race, poverty, and survival in multiple myeloma.Cancer. 1984; 54: 3085-3094Crossref PubMed Scopus (45) Google Scholar]. Prior comparisons have drawn conflicting conclusions on treatment outcomes among Blacks compared with White patients with MM. Savage et al. [13Savage D. Lindenbaum J. Van Ryzin J. Struening E. Garrett T.J. Race, poverty, and survival in multiple myeloma.Cancer. 1984; 54: 3085-3094Crossref PubMed Scopus (45) Google Scholar, 14Cella D.F. Orav E.J. Kornblith A.B. et al.Socioeconomic status and cancer survival.J Clin Oncol. 1991; 9: 1500-1509PubMed Google Scholar] found that Black patients had shorter survival times following similar therapy for MM. Presentation at later stages of disease, socioeconomic factors, or differential access to care were thought to explain this disparity. Other investigators have suggested that these disparities in outcomes are primarily because of biological characteristics [15Lyn D. Cherney B.W. Lalande M. et al.A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer.Am J Hum Genet. 1993; 52: 124-134PubMed Google Scholar, 16Cao J. Hong C.H. Rosen L. et al.Deletion of genetic material from a poly(ADP-ribose) polymerase-like gene on chromosome 13 occurs frequently in patients with monoclonal gammopathies.Cancer Epidemiol Biomarkers Prev. 1995; 4: 759-763PubMed Google Scholar]. Randomized clinical trials support the use of autologous hematopoietic-cell transplant (AHCT) as a standard therapy for MM [17Attal M. Harousseau J.L. Stoppa A.M. et al.A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome.N Engl J Med. 1996; 335: 91-97Crossref PubMed Scopus (2569) Google Scholar, 18Child J.A. Morgan G.J. Davies F.E. et al.High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma.N Engl J Med. 2003; 348: 1875-1883Crossref PubMed Scopus (1574) Google Scholar]. We have previously shown that Blacks are less likely to receive AHCT for MM compared with their age- and sex-matched White counterparts [19Joshua T.V. Rizzo J.D. Zhang M.J. Horowitz M.M. Access to hematopoietic stem cell transplantation: effect of race and gender.Biol Blood Marrow Transplant. 2007; 13: 22Abstract Full Text Full Text PDF Google Scholar]. In the current study, we compared outcomes between Black and White patients receiving AHCT for MM to determine if disparate post transplant outcomes validate lower AHCT use in Blacks. The Center for International Blood and Marrow Transplant Research (CIBMTR) consists of a voluntary working group of more than 450 transplant centers worldwide. Centers contribute detailed data on consecutive allogeneic and autologous transplants to a statistical center at either the Medical College of Wisconsin in Milwaukee or the National Marrow Donor Program (NMDP) Coordinating Center in Minneapolis. Subjects are followed longitudinally, with yearly follow-up. Computerized checks for errors, physicians' review of submitted data, and on-site audits of participating centers ensure data quality. Observational studies conducted by the CIBMTR are done with a waiver of informed consent and in compliance with HIPAA regulations as determined by the Institutional Review Board and the Privacy Officer of the Medical College of Wisconsin. The study included 2195 (303 Black and 1892 White) adult (aged ≥18 years) recipients of AHCT for MM who were transplanted between January 1995 and June 2005 (Table 1). Only recipients of peripheral blood (PB) AHCT were included in this study; patients who had received planned tandem AHCT (N=582) were excluded. Centers obtained information about patient race and then reported it to the CIBMTR.Table 1Patient CharacteristicsWhiteBlackVariableN (%)N (%)P-valueNumber of patients1892303Age median (range), years57 (27-80)55 (27-74)<.001Age group at transplant, years.002 <50396 (21)88 (29) 50-641111 (59)172 (57) ≥ 65385 (20)43 (14)Male sex1136 (60)164 (54).05Karnofsky score pretransplant.005 ≥901153 (61)210 (69)Hypertension<.001 Yes471 (25)143 (47)Diabetes<.001 Yes169 (9)50 (17)Body Mass Index.01 Underweight/normal (<25)557 (29)67 (22) Overweight (25-29.9)741 (39)120 (40) Obese/morbidly obese (≥30)594 (31)116 (38)Disease relatedDurie-Salmon stage at diagnosis.25 I203 (11)25 (8) II562 (30)101 (33) III1127 (60)177 (58)Immunochemical subtype of myeloma.34 IgG1003 (53)173 (57) IgA359 (19)45 (15) Light chain329 (17)54 (18) Others/unknown125 (11)16 (10)Albumin level at diagnosis.05 >3.5 g/dL732 (39)101 (33)Hemoglobin at diagnosis <10 g/dL<.001 <10 g/dL552 (29)135 (45)Creatinine at diagnosis.09 >1.5 mg/dL361 (19)74 (24)B-2 microglobulin level at diagnosis.83 ≥5.5 mg/L195 (10)31 (10)Prior chemotherapy regimens.78 MP ± others334 (18)50 (17) VAD ± others (not MP)1104 (58)182 (60) Cy ± others300 (16)52 (17) Corticosteroids ± others154 (8)19 (6)Number of lines of chemotherapy§.29 11125 (59)167 (55) 2536 (28)99 (33) >2231 (12)37 (12)Sensitive to chemotherapy prior to transplant.83 Sensitive1434 (76)228 (75)Disease status at time of transplant.67 Complete remission/partial remission1396 (74)231 (76)Treatment relatedTime from diagnosis to transplant median (range), months8 (<1-249)9 (2-217)<.001Time from diagnosis to transplant<.001 <12 months1364 (72)190 (63) ≥12 months528 (28)113 (37)Conditioning regimen.7 Melphalan only1417 (75)223 (74) Melphalan+TBI ± others204 (11)35 (12) Bu-Cy ± others (not TBI, not melphalan)271 (15)45 (15)Median follow-up of survivors, median (range)61 (<1-145)51 (<1-132)MP indicates Melphalan+Prednisone; VAD, vincristine + dexamethasone + adriamycin; Cy, cyclophosphamide; Bu, busulfan; TBI, total body irradiation; Eval, evaluable.§ Excludes stem cell priming. Open table in a new tab MP indicates Melphalan+Prednisone; VAD, vincristine + dexamethasone + adriamycin; Cy, cyclophosphamide; Bu, busulfan; TBI, total body irradiation; Eval, evaluable. § Excludes stem cell priming. Patient-, disease-, and treatment-related factors were compared between the Black and White cohorts, using a chi-square test for categorical and a Kruskal-Wallis test for continuous variables. Outcomes analyzed included nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). NRM was defined as death occurring in the absence of relapse or progression of MM following AHCT. Relapse/progression was defined according to standard criteria [20Blade J. Samson D. Reece D. et al.Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant.Br J Haematol. 1998; 102: 1115-1123Crossref PubMed Scopus (1474) Google Scholar]. Chemotherapy sensitivity was defined as achievement of a partial or complete response (PR, CR) to pretransplant therapy. PFS was defined as survival without disease progression or relapse. Patients alive and with of disease progression or relapse were at the time of last follow-up. The survival was defined as time from the of transplant to the of death or last and by a survival of OS and PFS were using the from Scopus Google Scholar, for and Google Scholar]. NRM and were using cumulative incidence The test was for was to the outcomes between Black and White patient and to risk factors associated with outcomes and Scholar]. multivariate was to that with a of was The for was by a for risk and that the were as risk factors found to be were in the The effect Black versus White) was included in The in multivariate are in were using in effect versus versus versus performance status at versus versus versus versus prior to versus prior to versus of prior to versus >1.5 versus at versus versus Light versus stage at versus versus of lines of versus 2 versus to chemotherapy prior to versus others Disease status prior to complete remission/partial versus others disease, disease and chemotherapy versus VAD versus Cy ± others versus Corticosteroids ± from diagnosis to <12 versus others versus ± others versus Bu-Cy ± others (not TBI, not versus of versus indicates Melphalan+Prednisone; VAD, vincristine + dexamethasone + adriamycin; Cy, cyclophosphamide; Bu, busulfan; TBI, total body Open table in a new tab MP indicates Melphalan+Prednisone; VAD, vincristine + dexamethasone + adriamycin; Cy, cyclophosphamide; Bu, busulfan; TBI, total body the characteristics of patients at AHCT were for Black compared to for White patients The Black cohort had a of and patients with Karnofsky performance status versus Blacks were more likely to have as versus versus and obesity versus differences in disease stage or MM subtype were Blacks were more likely to have a lower hemoglobin <10 in versus at diagnosis. differences in the levels of or marrow were The not with to the and of prior or sensitivity to transplantation. Blacks were transplanted later in the disease with receiving AHCT a or more from diagnosis versus in Whites were differences in or the of a AHCT. the cumulative incidence of The cumulative incidence of NRM was similar in groups. it was in Whites versus in Blacks. it was versus in Whites and Blacks, In multivariate (Table race was not associated with associated with an increased risk of NRM were and AHCT prior to for and prior to stage at diagnosis of lines of to chemotherapy prior to transplant from diagnosis to transplant <12 ≥12 of transplant indicates stem cell priming. Open table in a new tab indicates stem cell priming. 2 cumulative incidence of The cumulative incidence of was similar in groups. it was in Whites versus in Blacks. it was versus in Whites and Blacks, In multivariate (Table race was not associated with disease relapse or associated with an increased risk of relapse included score stage at of or more lines of chemotherapy of disease prior to AHCT ≥12 from and later of AHCT. the probability of The and 5-year probabilities of PFS were similar in groups. it was in Whites versus in Blacks. it was versus in Whites and Blacks, In multivariate (Table race was not associated with for and prior to stage at diagnosis of lines of to chemotherapy prior to transplant from diagnosis to transplant <12 ≥12 indicates stem cell priming. Open table in a new tab indicates stem cell priming. the probability of OS AHCT. The and 5-year survival rates were similar between the 2 it was in Whites versus in Blacks. it was versus in Whites and Blacks, In multivariate (Table race was not a of PFS and OS were in patients with at AHCT score who received 2 or more lines of therapy prior to AHCT ≥12 from and chemotherapy disease (Table OS was lower in patients who AHCT prior to The of mortality in was relapse or progression of MM that for of that Black and Whites have similar outcomes AHCT for MM. with in studies of therapy that the in outcomes for MM Blacks receive therapy S. et autologous stem cell transplantation in black patients with multiple Marrow Transplant. 2006; PubMed Scopus (18) Google Scholar]. investigators have shown that Blacks have outcomes similar to Whites the treatment for MM. et al. M. S. Chemotherapy and survival for patients with multiple from a and J Clin Oncol. 2007; PubMed Scopus Google Scholar] that Blacks were less likely to receive but with similar outcomes similar therapy for MM. In the pretransplant et al. J. of race as a in multiple myeloma. of Group Clin Oncol. 1996; Google Scholar] the impact of race in the of the study of chemotherapy for MM. study in the United States, Black and White patients were shown to have similar median survival and were differences by stage or MM study from the of equal access health care reported on the outcomes of Black and White patients receiving AHCT for MM and outcomes between the 2 The impact of race on outcomes of autologous transplantation in patients with multiple J 2008; PubMed Scopus Google Scholar]. In their study, were differences in the or although Blacks have levels and a for less The a study as the current Other center Black and White recipients of AHCT for MM have drawn conflicting et al. et in blacks with multiple Marrow Transplant. PubMed Scopus Google Scholar] analyzed Black patients and that were likely to relapse AHCT. was not compared in this et al. S. et autologous stem cell transplantation in black patients with multiple Marrow Transplant. 2006; PubMed Scopus (18) Google Scholar] in their study that included Black and White AHCT found that Black patients had more and greater survival is that Blacks are less likely to receive chemotherapy for MM as well as AHCT. et al. M. S. Chemotherapy and survival for patients with multiple from a and J Clin Oncol. 2007; PubMed Scopus Google Scholar] of chemotherapy use for patients with MM the clinical trial a cohort of patients or with stage or MM, found that only received Blacks were less likely to receive chemotherapy compared to Whites versus that use of chemotherapy myeloma and increased survival M. S. Chemotherapy and survival for patients with multiple from a and J Clin Oncol. 2007; PubMed Scopus Google Scholar]. The reasons for the disparate access are because for socioeconomic status not the in the of disparities in the of therapy in the transplant as et al. [19Joshua T.V. Rizzo J.D. Zhang M.J. Horowitz M.M. Access to hematopoietic stem cell transplantation: effect of race and gender.Biol Blood Marrow Transplant. 2007; 13: 22Abstract Full Text Full Text PDF Google in a study from the that Whites are more likely to receive AHCT for MM compared to an age- and Black data from the SEER and CIBMTR the study that age- and of receiving AHCT for MM is times greater in Whites compared to Blacks. study the reasons for this of AHCT in Blacks, conclusions be drawn AHCT for MM in Black It has that access to treatment for MM may be to or outcomes in Black study that outcomes are not between Blacks and Whites receiving AHCT for MM, suggesting this treatment be to patients are in with a of patients treated for survival in the of was similar between treatment was D. Brawley O.W. A. S. of blacks and whites a cancer PubMed Scopus Google Scholar]. The pretransplant characteristics of Black recipients of AHCT are The Black cohort was younger and had better performance status than the White rates of and at diagnosis. differences likely a Black patients with lower with to for of AHCT. Black patients were likely to have had a time between diagnosis and transplantation compared to Whites, receiving a similar of chemotherapy and similar for of AHCT. only the Black patients for transplant may be in patients with less clinical may only be or The of study is the of transplant centers it likely that these are to the transplant as a In this we are to any conclusions about factors associated with of transplant in Blacks because a is not The characteristics of the of black MM patients not receiving AHCT need to be analyzed to the of a of AHCT. It is that Blacks who are not receiving stem cell transplantation for myeloma are the transplant by it is that access to compliance to clinical and socioeconomic disparities for of the differences in of AHCT for patients with MM. the of equal outcomes for Blacks with MM, further study and to ensure better and of transplant for the Black is The CIBMTR is by from the National Cancer the National and Blood and the National of and a from and a with and 2 and from the of and from for Blood and Marrow to the Medical College of of Medical and Disease Blood Center of and Marrow Blood and Marrow Transplant Centers for Disease and and an European Group for Blood and Marrow Medical of The Medical College of Blood National Marrow Donor Blood for Epidemiology of The Marrow and The in this not the or of the National of the of the the of or any of the

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