Survival Disparities Between African-American and Caucasian Patients with Multiple Myeloma Are Blunted in the Era of Novel Therapeutics and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1395-1395 ◽  
Author(s):  
Nina Shah ◽  
Donna M Weber ◽  
Michael Wang ◽  
Sheeba Thomas ◽  
Jatin Shah ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
African American ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Stage I ◽  
Single Center ◽  
Novel Therapeutics ◽  
Caucasian Patients

Abstract Abstract 1395 Poster Board I-417 Background: Multiple myeloma accounts for approximately 10% of hematologic malignancies diagnosed annually in the U.S. It is well documented that the African-American population is disproportionately affected by multiple myeloma in incidence and mortality. Survival data from the SEER database from 2001-2005 demonstrated higher mortality in African-American patients compared to Caucasian patients. However, more recent retrospective reviews in the era of autologous stem cell transplant (ASCT) did not support this finding. Thus the persistence of racial survival disparities in the era of ASCT and novel therapeutics is an evolving question. Methods: We performed a retrospective review of 170 African-American multiple myeloma patients and 170 age and gender-matched Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2008. Results: Three hundred forty previously untreated patients were analyzed. Median age at diagnosis was 57 years for both groups. For evaluable patients, the International Staging System at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 53%, 28% and 19% respectively. The percentage of stage I, II and III patients in the Caucasian group was 40%, 30% and 29% respectively. These staging data were not significantly different between racial groups. In both groups, 89% of patients received a novel therapeutic (thalidomide, lenalidomide or bortezomib) during their treatment course. We found a statistically significant difference in the percentage of African-American and Caucasian patients who received high dose chemotherapy and ASCT (65% and 76%, respectively, p=0.04). There was no difference observed in the number of second transplants performed in the two groups (19 in both groups). Response to therapy is detailed in Table 1. There was no difference in overall response to any therapy of evaluable patients between the two groups. With a median follow-up time of 35 months, the median overall survival from diagnosis has not been reached in either group. Kaplan-Meir analysis shows that there is no difference in overall survival between black and white patients (p =0.1) Conclusions: In this single-center, retrospective study of multiple myeloma patients treated predominately with novel agents, with or without ASCT, no survival difference was observed between African-American and Caucasian patients. To our knowledge, this is the largest number of African-American myeloma patients analyzed for survival in a single-center study. Recognizing the potential disparities in healthcare access, this may not represent outcomes for all African-American patients with myeloma. Since median overall survival has not been reached in this data, it is possible that survival differences will become apparent in the future, and further follow-up is needed. However, this review suggests that in the era of novel therapeutics and ASCT resulting in improved overall response rates, survival in African-American patients may be equivalent to Caucasian patients. Further efforts are needed to enroll African-American patients on clinical trials to validate this observation prospectively. Disclosures: No relevant conflicts of interest to declare.

Effect of Amp5q31 and Del12p13 on Survival of Patients with Multiple Myeloma Treated with Novel Agent-Based Regimens: A Single Center Experience on 172 Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1811-1811
Author(s):  
Evangelos Terpos ◽  
Efstathios Kastritis ◽  
Despoina Iakovaki ◽  
Maria Gkotzamanidou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Survival ◽  
Chromosomal Aberrations ◽  
Median Overall Survival ◽  
Chromosomal Abnormalities ◽  
Newly Diagnosed ◽  
Single Center ◽  
Agent Based ◽  
Novel Agent

Abstract Abstract 1811 The presence of chromosomal aberrations is a characteristic feature of multiple myeloma (MM). Recently, Avet-Loiseau et al reported that amp5q31.3 and del12p13.31, detected by high-density, single-nucleotide polymorphism arrays analysis correlate with prognosis in MM patients who were treated upfront with conventional chemotherapy (JCO 2009; 27:4585–90). The aim of our study was to evaluate the effect of these chromosomal abberations on survival of patients with newly diagnosed MM or with relapsed/refractory myeloma who were treated with novel agent-based regimens. We studied 172 MM patients who were treated in a single center in Athens (Greece) during a 4-year period (2007–2011); 76 were newly-diagnosed and were treated upfront with either bortezomib- or IMiD-based regimens and 96 had relapsed or refractory MM and were treated with the combination of lenalidomide and dexamethasone with or without bortezomib (RD vs. VRD) based on the presence of previous peripheral neuropathy (Dimopoulos et al, Leukemia 2010;24:1769–78). A combined methodological approach of G-banding karyotypic analysis and interphase fluorescence in situ hybridization (FISH) was performed in all patients. G-banding analysis was performed according to the European Cytogenetic Guidelines and Quality Assurance (ECA, 2006). The clonality criteria and the karyotypic description followed the recommendations of the International System for Human Cytogenetic Nomenclature (ISCN, 2009). FISH was performed according to the Recommendations for FISH in MM (European Myeloma Network) on uncultured BM, either on cytoplasmic immunoglobulin-enhanced cells (cIg-FISH) or on nuclei from purified CD138+ plasma cells. Commercially available DNA probes (Abott-VYSIS) were used for the detection of del17p, del13q, add1q21, t(4;14) and t(14;16). The probes RP11-96J7 and RP11-578N7 (labeled by Empire Genomics, NY, USA) were used to detect amp5q31 and del12p13. The frequency of the studied chromosomal abnormalities is depicted in the table. There was a strong correlation between the presence of amp5q31 with hyperdiploidy (p=0.012) but amp5q31 did not correlate with the presence of any other of the studied chromosomal aberrations. The presence of del12p13 was correlated with the presence of del13q (p=0.001), t(4;14) (p=0.009) and del17p (p=0.005). Add1q21 also correlated with del13q (p<0.001), t(4;14) (p<0.001) and del17p (p=0.007). In patients with relapsed/refractory MM, who received either RD or VRD, the median overall survival was 19 months. Patients with amp5q31 had a median survival of 18 months (95% CI: 13–23 months) vs. 21 months of the others (95% CI: 8–35 months; p=0.737), while patients with del12p13 had a median survival of 27 months (95% CI: 0–57 months) vs. 19 months of the others (95% CI: 10–27 months; p=0.767). Of the other studied cytogenetic abnormalities, the presence of del17p (11 vs. 26 months; p=0.001), amp1q21 (12 vs. 26 months; p=0.001) and del13q by FISH (11 vs. 26 months; p=0.025), but not of t(4;14) (p=0.521), were associated with inferior overall survival. In patients with newly-diagnosed MM, the median overall survival was 57 months. The median survival of patients with amp5q31 was 46 months vs. 57 months of all others (p=0.315) and for patients with del12p13 has not been reached vs. 57 months of all others (p=0.379). In conclusion, amp5q31 and del12p13 are recurrent chromosomal abnormalities in MM. Amp5q31 is not associated with the presence of other genetic features, except hyperdiploidy. αmp5q31 or 12p13 was not predictive of survival ιn our series. However, further studies are needed in patients with newly diagnosed MM who receive novel agents upfront to validate the prognostic importance of amp5q31 and del12p13.TableCytogenetic abnormalityPatients at diagnosis (n=76)Relpased/refractory patients (n=96)p-valueamp5q3112 (15.7%)20 (20.8%)0.271amp5q31 as sole anomaly5 (6.5%)7 (7.2%)0.674del12p138 (10.5%)16 (16.6%)0.171del13q28 (36.8%)28 (29.1%)0.279del17p13 (17.1%)15 (15.6%)0.765add1q2115 (19.7%)26 (27%)0.303t(14;16)1 (1.3%)1 (1%)0.832t(4;14)4 (5.2%)10 (10.4%)0.221Hyperdiploidy/hypodiploidy10 (13.1%)/6 (7.8%)11 (11.4%)/13 (13.5%)0.301 Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of 3q21 and 3q26 Cytogenetic Abnormalities in Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2594-2594
Author(s):  
Mario Annunziata ◽  
Piera Angelillo ◽  
Laura Vicari ◽  
Clelia Criscuolo ◽  
Felicetto Ferrara
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Platelet Count ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Chromosome 3 ◽  
Prognostic Impact ◽  
Acute Myeloid

Abstract Abstract 2594 Background: Abnormalities affecting long arm of chromosome 3 are rare but recurrent in Acute Myeloid Leukemia (AML) and are detected in a variable percentage of AML patients according to different series. The 2008 World Health Organization classification recognizes AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) as a distinct subtype characterized by a poor prognosis. Allogeneic stem cell transplantation seems to improve outcome in eligible patients with these aberrations. Inappropriate expression of the ecotropic viral integration site 1 (EVI1) was demonstrated in virtually all patients with t(3;3)(q21;q26.2) and inv(3)(q21q26.2); as well as in a majority of patients with other 3q26 rearrangements. Other chromosome 3 abnormalities are rarely recognized in AML patients; clinical and prognostic relevance of these alterations is not yet defined. The aim of this study is to assess the prognostic impact of chromosome 3 abnormalities on disease characteristics and treatment outcome in AML. Patients and methods: A total of 580 consecutive adult patients were diagnosed with AML at our institution between February 2002 and July 2012. Conventional cytogenetic analysis performed on diagnostic bone marrow samples detected the presence of 3q abnormalities in 16 patients (2.7%). Two patients were lost to follow-up and were not evaluated for survival analysis. Molecular status of FLT3 and NPM1 was also performed and results are available for 10 patients. Median follow-up time for patients in this series was 47 months ( range 6–125). Results: There were 10 male and 6 female patients, the median age being 64.5 years (range 33–81), 10 patients had de novo AML while 6 evolved from a previously diagnosed myelodysplastic syndrome (MDS). Karyotype from MDS phase was available in 2 patients; both acquired 3q rearrangement at time of progression to AML. At time of diagnosis median haemoglobin value was 9.0 g/dL (range 4–11); median leucocyte count was 10.5 × 103̂/L (range 2.3 – 431). Median platelet count was 116 × 109̂/L (range 28 – 529), consistently with previous studies, which have shown that these patients present with higher platelet count at diagnosis when compared with no 3q rearranged ones. Regarding cytogenetic features 3 patients had t(3;3)(q21;q26), 3 patients had inv(3) (q21; q26), 3 patients showed a balanced rearrangement involving 3q26, while 6 patients harbored a del3q. One patient showed monosomy 3. Additional chromosomal changes were demonstrated in 5 patients, two of them had a complex karyotype (see Table 1), 3 had a monosomy 7. Thirteen patients out of 14 received intensive induction chemotherapy; complete remission (CR) was achieved in 5 patients (CR rate: 35.7%), the remaining 7 patients were resistant to induction as well as to salvage chemotherapy. Four patients underwent autologous stem cell transplantation. Median overall survival in this series is 5.5 months (range 0 – 20). At present only one patient is still alive and in CR, 20 months after diagnosis. Median disease free survival (DFS) for patients achieving a CR was 9 months (range 6–20). Median overall survival for patients resistant to first-line therapy was 3 months (range 0–6). Clinical features and treatment outcome of the patients are summarized in Table 1. Conclusions: The incidence of 3q abnormalities in our single institution series is 2.4%, in keeping with previous studies. Our findings confirm the association between these alterations and thrombocytosis at diagnosis, preceding MDS or multilineage dysplasia, presence in all FAB subtypes (except M3), association with additional chromosomal abnormalities as well as the poor response to conventional chemotherapy (CR rate 35.7%), and very short DFS in spite of obtaining CR. Disclosures: No relevant conflicts of interest to declare.

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

Multiple Myeloma Profile In Latin America: Clinical and Epidemiological Observational Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5327-5327
Author(s):  
Vania T M Hungria ◽  
Angelo Maiolino ◽  
Gracia Aparecida Martinez ◽  
Carmino A De Souza ◽  
Rosane Bittencourt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Latin America ◽  
Clinical Features ◽  
Median Overall Survival ◽  
High Dose Chemotherapy ◽  
Patterns Of Care ◽  
Disease Stage ◽  
High Dose

Abstract Introduction Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries. Objective To characterize the demographic and clinical features of patients with multiple myeloma from five LA countries (Brazil, Argentina, Chile, Mexico and Peru) and to create a LA database on MM; in addition to investigating the patterns of care for MM patients in Latin America. Patients and Methods This is an observational, non-intervention study, with a prospective evaluation of data. Eligible patients were diagnosed with multiple myeloma, between January 1, 2005, and December 31, 2007, at any one of the participating centers, regardless of disease stage or treatment modality. The follow-up period extended to at least 5 years for each patient (December 31, 2012). Results Eight hundred and seventy six patients were included. The median age was 60 years old (25-97), 53.4% male and 46.6% female. The median follow-up was 31.4 months, and the median overall survival was 57 months. The median overall survival to patients who received high-dose chemotherapy was 77 months and for patients who received conventional chemotherapy was 48 months (p<0.001). The multivariate prognostic model included patient baseline variables that were associated with mortality in the Kaplan-Meier univariate analyses. Only hypercalcemia, DSS II and III, ISS stage III andnon- high-dose chemotherapy were independent predictors of mortality. Conclusion This current study, which is the largest case series of MM patients in Latin America, recognizes the feasibility of large, collaborative, observational studies among various tertiary-care hematology centers in Latin America. Note We will present more details related to the demographic and most frequently used treatments in Latin America for newly diagnosed and relapsed patients in these LA countries. Disclosures: No relevant conflicts of interest to declare.

Long Term Significance of Response in Multiple Myeloma After Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1811-1811
Author(s):  
Joaquin Martínez-López ◽  
Joan Blade ◽  
M. Carmen Gomez del Castillo ◽  
Maria Victoria Mateos ◽  
Adrian Alegre ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Complete Response ◽  
Long Term Follow Up

Abstract Abstract 1811 Poster Board I-837 The prognostic significance of achieving complete remission (CR) in Multiple Myeloma (MM) has finally been accepted. However, available studies have been based on series with a median follow-up around 5 years. This time period is insufficient according to the current life expectation of MM. Aim To establish the real effect of prognosis of the different response categories in a cohort of MM patients treated with autologous stem cell transplantation (ASCT) after long term follow up. Patients and methods Follow-up from diagnosis of 344 MM patients transplanted between 1989 and 1998 has been updated. These patients were previously included in a study aimed at establishing the post-ASCT response significance in MM and to validate the EBMT classification (Br J Haemat 2000;109:438-46). It was possible to update the follow up of 322 patients as at April 2009. At this date 99 patients were alive with a median follow-up form diagnosis of 12.5 years. Response categories and evaluated cases were: i) Complete Response (IF-) (CR), n= 84 ii) near Complete Response (EF-/IF+) (nCR), n= 66 iii) Very good partial response (VGPR) (<90% reduction of M component), n= 66 iv) Partial response PR (reduction of M component between 90-50%), n= 113 v) Stable Disease (SD), n= 12, y vi) Progression (PD), n=14 Survival analyses were performed by Kaplan-Meier curves (log-rank test). Cox logistic regression was employed to establish variables associated with a higher survival. Results Significant differences in overall survival (OS) and event free survival (EFS) were found between CR and nCR groups (p 0.01 and 0.0022, respectively); or between CR and VGPR (p 0.0001 and 0.0035); no differences were detected between nRC and VGPR groups (p 0.21 and 0.99) and between these groups and PR group (p 0.1 y p 0.8). OS and EFS of patients with ED o PD were lower than the rest of the groups. Overall survival at 12 years was 43% in CR patients, 21% in nCR, 20% in VGPR, 30% in PR, 8% in SD and 0% in PD groups. Median survival (OS, EFS respectively) of each group was 91 months and 36 m, 26 m and 21 m, 20 m and 15 m, 31 m and 12 m, 8 m and 5 m, and 6 and 1 month. Land-mark study (10 years) found a plateau phase in OS and EFS after 11 years. Twenty two percent of patients are still alive with stable status between 11 and 15.54 years and only two cases had relapsed in the non CR group. In a regression study for OS, response was only one variable with statistical significance (CR P <0.0000, OR 0.044, IC-95%: 0.020-0.30). Conclusions In MM achieving CR after ASCT is the most important prognostic factor even after long-term follow-up. Relapse rate is very low in patients with >11 years of follow-up, this could mean a cure for patients in CR. Disclosures No relevant conflicts of interest to declare.

Salvage Autologous Hematpoeitic Stem Cell Transplants (AHSCT2) for Myeloma: Single Center Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4591-4591
Author(s):  
Bishoy Faltas ◽  
Jane L. Liesveld ◽  
Michael Becker ◽  
Jainulabdeen J. Ifthikharuddin ◽  
Gordon L. Phillips
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
High Dose ◽  
The Impact

Abstract Abstract 4591 Although the role of AHSCT1 is well established in multiple myeloma therapy, the role of the salvage (not “tandem”) AHSCT2 is less clear. However, most pts. undergo initial stem cell harvests with plans for eventual AHSCT2. To clarify the indications, the prognostic factors and the outcomes of AHSCT2 in relapsed myeloma, we analyzed our experience in 19 pts. (pts.) who underwent salvage AHSCT2 between the 1994–2008. Mean age at AHSCT1/2 was 54.58 (SD 7.96)/57.03 (SD 8.10) respectively; 15 (79.0%) were males. At the time of diagnosis, 7 (36.8%) pts. had ISS stage I, 6 (31.6%) stage II, 3(15.8%) stage III and in 3 (15.8%) the ISS stage could not be determined. Isotypes: IgG 11 (57.9%), IgA 4 (21.1%), 1 (5.3%) pt. had IgM and 3 (15.8%) had light chain myeloma. Cytogenetics were normal in 6 (31.6%), abnormal in 5 (26.3%) and unavailable for 8 (42.1%) pts. The most common therapy received prior to AHSCT1 was Vincristine/Adriamycin/Dexamethasone in 11 (57.9%) pts.; 7 pts. were exposed to novel agents. One pt. achieved complete response (CR), 15 (79.0%) pts. achieved partial response (PR) and 3 (15.8%) pts. had stable or progressive disease after receiving the initial treatment. All pts. proceeded to receive high dose therapy with Melphalan (MEL), 2 pts received fTBI in addition to MEL. Mean MEL dose was 190.00 mg/m2 (SD 23.01); 15 pts. received 200 mg/m2. All pts. received >2×10e6/kg of CD34+ cells in the first and second transplants. At D+100 after AHSCT1, responses were: 4 (21.1%) CR, 1 (5.3%) VGPR, 8 (42.1%) PR and 6 (31.6 %) with lesser responses. Therapy to prolong response or for salvage after AHSCT1 was given in all pts before AHSCT2, including Thalidomide in 6 (31.6%), Bortezomib in 4 (21.1%) and Lenalidomide in 2 (10.5) pts. Median time to progression after AHSCT1 was 318 days [95 % CI 110– 573]. Median interval between AHSCT1 and AHSCT2 was 896.74 days (SD: 698.34 days). At the time of AHSCT2, 4 (21.1%) were in PR, 15 (79.0%) had progressive disease. For AHSCT2, all pts. Received MEL, one pt. received MEL + Cytoxan and one pt. received MEL + Bortezomib. The median MEL dose/m2 was 175.56 (52.04).All pts. survived AHSCT2 to D+100, responses were as follows: 3 (15.8%) VGPR, 9 (47.4%) in PR; 7 (36.9) pts. had lesser responses. After AHSCT2, nine (47.4%) pts. had grade III toxicity and only one pt. had grade IV toxicity (avascular necrosis). Maintenance therapy after AHSCT2 included Bortezomib in 7 (36.8%) pts., Lenalidomide in 5 (26.3%) pts. and Thalidomide in 4 (21.1%) pts. After AHSCT2, the median overall survival (OS) was 658 days [95 % CI 326–1330] and progression free survival (PFS) after AHSCT2 was 237 days [95 % CI 121– 397] (Figure 1). OS probability at 6, 12, 24 months after AHSCT2 was 81.3, 75.0, 39.3 % respectively. For all pts., the median OS time (i.e. time from diagnosis to death or last follow-up) was 2187 days [95% CI 1413– 4126]. At the end of the follow up period, a total of 14 pts. had died. Causes of death were progression in 12 (63.2%) and sepsis in 2 pts. (10.5%). The number of previous lines of chemotherapy, interval between transplants, disease status at the time of AHSCT1/2, type of myeloma and MEL dose were not predictive of OS and PFS. In the multivariate analysis, only age by decade at AHSCT2 and male gender were independent predictors of OS after AHSCT2 (HR 4.037, P= 0.01), (HR 3.74, P=0.07) respectively. Similarly, in the multivariate analysis for PFS after AHSCT2, age at AHSCT2 was an unfavorable independent predictor (HR 3.48, P=0.009) whereas relapse free response more than 18 months after AHSCT1 was an independent favorable predictor (HR 0.198, P=0.007).Our results are consistent with the few studies examining the impact of salvage transplants for myeloma which report a median overall survival ranging from 20.7 to 38.1 months from the time of AHSCT2.We conclude that salvage AHSCT2 can positively impact PFS and OS but efforts to improve outcomes are mandatory.FigureSEQ Figure ≂,* ARABIC 1Figure. SEQ Figure ≂,* ARABIC 1 X-axis represents time from AHSCT2 in days. Y axis represents survival distribution. Blue line = OS, Red = PFS. Disclosures: No relevant conflicts of interest to declare.

Importance of Achieving Sustained Stringent Complete Response (sCR) Following Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1988-1988
Author(s):  
Prashant Kapoor ◽  
Morie A Gertz ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
David Dingli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Response Category ◽  
Landmark Analysis

Abstract Abstract 1988 Background With the utilization of novel agent-based combination therapies and autologous stem-cell transplantation (ASCT) in multiple myeloma (MM), the rigorous response category of stringent complete remission (sCR) in the international uniform response criteria is increasingly becoming attainable. In addition to the standard criteria for complete remission (CR), sCR requires normalization of the free light chain ratio and disappearance of clonal cells as determined by the marrow immunofluorescence or immunohistochemistry. We have previously validated the new response category of sCR created in by the International Myeloma Working Group and demonstrated that sCR represents a deeper level of response, translating into a superior OS. Herein we report the survival outcomes of patients attaining sCR or standard CR, from a 2-year landmark after ASCT in a cohort of patients with extended follow-up. Additionally, we report the outcome of patients who remained in sCR for at least 6 months (sustained-sCR) after ASCT. Patients and Methods Maximal response rates of four hundred and forty-five consecutive patients who underwent ASCT within 12 months of diagnosis of MM were determined. The population achieving varying degrees of complete remission (n=237) is the focus of this study. We performed a landmark analysis 2 years after ASCT to ensure that all the patients attaining at least CR had sufficient time to reach the response levels being studied. Patients were categorized as having sustained sCR (sus-sCR) if the duration of sCR was at least 6 months. Overall survival (OS) was estimated by the Kaplan Meier method and the survival curves were compared by log-rank test. Results The median follow-up of the entire cohort was seventy-seven months (95% CI: 73–82 months). The sCR rate after ASCT was 24% (n=109). Median time to progression (TTP) of patients attaining sCR was 50 months from ASCT, and median overall survival (OS) is not reached, in contrast to those attaining standard CR (n=37, TTP=20 months, OS=81 months) or near CR/nCR (n=91; TTP= 19 months, OS=60 months, p<0.0001 for both TTP and OS). OS of patients surviving at least 2 years from ASCT (Figure 1a) continued to remain superior for those attaining sCR (n=105, median: not reached) versus 70 months for the CR group (n=32; p=0.004). Among patients achieving sCR (n=109), OS of patients with sus-sCR (n= 75) at 6 months from ASCT is not reached (5-year OS=91%, 7-year OS=86%) versus median OS of 66 months (5-year OS=49%, 7-year OS=37%; p<0.0001) for those who had non-sustained-sCR (n=34) after ASCT (Figure 1b). Conclusion In our landmark analysis of patients with MM who survived at least 2 years from ASCT, those attaining sCR have a markedly superior outcome compared to those attaining standard CR. However, among patients attaining sCR, those with sustained sCR of 6 months or greater had the best outcome. Myeloma trials reporting response rates should identify patients achieving sCR and CR separately owing to markedly disparate outcomes of the two categories. Disclosures: No relevant conflicts of interest to declare.

Lenalidomide Maintenance After Stem-Cell Transplantation For Multiple Myeloma: Follow-Up Analysis Of The IFM 2005-02 Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 406-406 ◽  
Author(s):  
Michel Attal ◽  
Valérie Lauwers-Cances ◽  
Gérald Marit ◽  
Denis Caillot ◽  
Thierry Facon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Placebo Group ◽  
Disease Progression ◽  
Group Versus ◽  
Cell Transplant ◽  
Second Line ◽  
First Line

Abstract Methods and Patients This randomized, placebo-controlled, phase 3 trial investigated the efficacy of lenalidomide (LEN) maintenance after transplantation for multiple myeloma. Patients, under 65 years of age, with non-progressive disease after a first-line autologous stem-cell transplant (ASCT) were randomized to receive maintenance with placebo or LEN (10 to 15 mg/d) until disease progression or unacceptable toxic effects. From July 2006 to August 2008, 614 patients were randomized. In January 2011, the DSMB recommended to stop LEN due to the increased incidence of second primary malignancies (SPMs). The median duration of maintenance treatment with LEN was 2 years (IQ range= 1-3). We previously reported this trial with a median follow-up of 45 months (Attal et al, N Engl J Med 2012). Results As of May 2013, median follow-up was 70 months from diagnosis and 60 months from randomization. LEN maintenance improved the 5-year progression-free survival (PFS) post randomization: 42%, versus 18% with placebo (p<0.0001), respectively. Overall, 403 patients had disease progression and 364 have started a second line therapy. The median 2nd PFS for the treated patients (time from progression in first-line to the second progression or last follow-up or death) was 10 months within the LEN arm versus 18 months within the placebo arm (p<0.0001), respectively. The median 2nd PFS in the LEN and placebo groups were 9 and 8 months (NS) for patients treated with a bortezomib-based regimen, 8 months and 18 months (p<0.01) for patients treated with an IMiD-based regimen, 14 months and 28 months (p=0.03) for patients treated with a regimen without new agents or with a second line ASCT, respectively. The 5-year post randomization overall survival (OS) was similar in the 2 groups: 68% in the LEN group versus 67% in the placebo group (HR=1). In the multivariate analysis, the OS was significantly related to age (p=0.001), International Staging System (p=0.03), and poor cytogenetics (t(4;14) or chromosome 17 deletion; p=0.008). The median survival after the first progression was 29 months in the LEN group versus 48 months in the placebo group (p< 0.0001). An increased incidence of SPMs was observed in the LEN group: 44 SPMs (hematologic: 20, non-hematologic: 24) in 35 patients were reported in the LEN group versus 28 SPMs (hematologic: 6, non-hematologic: 22) in 20 patients in the placebo group. The incidence of SPMs (excluding non melanoma skin cancers) was 2.3 per 100 patient-years in the LEN group versus 1.3 in the placebo group (p=0.03). Conclusion This new analysis confirms that lenalidomide is an effective treatment to prolong PFS after transplantation for multiple myeloma patients. However, this impressive benefit is not currently associated with an improved overall survival, due to a shorter survival after the first progression. Disclosures: Attal: CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Off Label Use: FRONTLINE THERAPY WITH CARFILZOMIB IN MULTIPLE MYELOMA. Facon:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Hulin:JANSSEN: Honoraria; CELGENE: Honoraria. Moreau:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Roussel:JANSSEN: Honoraria; CELGENE: Honoraria. Avet-Loiseau:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau.

Disparities in utilization of autologous stem cell transplantation as consolidative therapy for multiple myeloma: A single-institution retrospective review.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20504-e20504
Author(s):  
Oleksandra Lupak ◽  
Xiaoxia Han ◽  
Neha Patil ◽  
Kannan Thanikachalam ◽  
Peter Xie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
African American ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Survival Time ◽  
Cell Transplantation ◽  
Retrospective Review ◽  
Transplant Outcomes ◽  
Related Mortality

e20504 Background: Multiple Myeloma (MM) accounts for about 17% of hematologic malignancies in the United States. It is a disease of older adults, with a median age at diagnosis of 66 years. The incidence in African Americans is 2 to 3 times more that in Whites, and this disparity has been found to be greater among patients less than 50 years. Most guidelines recommend induction therapy with a triplet regimen followed by autologous hematopoietic cell transplantation (HCT). Unfortunately, racial and ethnic minorities have been found to be less likely to receive ASCT. A SEER-Medicare database analysis from 2000 to 2011 noted a lower utilization of ASCT and Bortezomib among black patients. The goal of this study was to evaluate patterns of acceptance of ASCT as consolidative therapy of MM. Because the receipt of upfront ASCT is dependent on response to induction therapy, our study also investigated disparity in transplant outcomes and time to transplant, which are areas that previous studies had not looked at. Methods: In this retrospective review we used Cox PH model to investigate the association between the survival time of the patients (OS) and age of the diagnosis, race, socioeconomic status, disease cytogenetic, and initial induction regimens. 194 patients with a confirmed diagnosis of MM who were referred for autologous hematopoietic stem cell transplantation (ASCT) between January 1st 2009 and June 30st 2019 were included in this study. Patients who received ASCT for relapsed MM were excluded. Results: Using Cox PH model, we found that high risk cytogenetic were significantly associated with shorter overall survival, higher transplant related mortality and relapse related mortality (P < 0.002). Use of aggressive induction choices was associated with poorer transplant outcomes (P 0.02). Time to transplant tended to be shorter in African American compared to other ethnic groups (P 0.07). Income category was not significantly associated with overall survival, time to transplant or transplant / relapse related mortality. Conclusions: Cytogenetic continues to be a significant factor in transplant outcomes affecting overall survival. Time to transplant tended to be shorter in African American comparing to others, potentially reflecting the differences in disease course. Our study provides a more real life data on ASCT outcome patterns. It is hoped that the results of this study will better guide interventions to improve utilization of ASCT as consolidative therapy for MM.

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