Selection of Unrelated Allogeneic Hematopoietic Cell Donors Based on KIR3DL1 Allotypes Is Feasible and Results in Improved Disease-Free Survival in Transplant Recipients with MDS and AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 990-990
Author(s):  
Brian C. Shaffer ◽  
Glenn Heller ◽  
Jean-Benoit Le Luduec ◽  
Jack Vahradian ◽  
Miguel Perales ◽  
...  
Keyword(s):  
Research Funding ◽  
Disease Free Survival ◽  
Hematopoietic Cell ◽  
No Donors ◽  
Free Survival ◽  
Inhibitory Signal ◽  
Improved Outcomes ◽  
High Degree ◽  
Disease Free ◽  
Selection Of

Abstract Donor natural killer (NK) cells impart a potent anti-leukemia effect after allogeneic hematopoietic cell transplantation (allo HCT). The killer Ig-like receptors (KIR) play a central role in modulating NK effector function. Chief among them, the inhibitory KIR3DL1 exhibits a high degree of allelic polymorphism. We previously demonstrated that highly expressed KIR3DL1 alleles (KIR3DL1 allele groups *001 and *002) bind preferentially to HLA-Bw4 with I80 to confer a high degree of inhibitory signaling. Similarly, poorly expressed KIR3DL1 alleles (KIR3DL1 allele groups *005 and *007) bind to HLA-Bw4 with T80 to confer a strong inhibitory signal. In a retrospective cohort of 299 patients undergoing allo HCT for AML, we demonstrated that these highly inhibitory donor KIR3DL1/recipient HLA-Bw combinations (KIR3DL1-HIGH) resulted in a greater incidence of recipient relapse when compared to other donor/recipient KIR3DL1/HLA-Bw pairings with low or absent inhibitory signal (KIR3DL1-LOW/NO). (Giglio F et al, ASH Annual Meeting Abstracts, 2012) Here, we evaluated whether it was feasible to prospectively type and use KIR3DL1 allotypes in unrelated allo HCT donor selection, and whether this intervention would result in improved outcomes in patients undergoing transplant for AML and MDS. We performed PCR-SSP based intermediate resolution KIR3DL1 allele typing on all unrelated adult donors evaluated for patients with MDS and AML at our center from 2013 to present as previously described. (Boudreau J et al, PLoS One, 2014) KIR3DL1 status was provided to the treating physicians, who made the final donor selection. A total of 941 prospective allo HCT donors underwent high resolution HLA typing and KIR3DL1 allotyping for 252 patients (median per patient = 4, range 1-12). Among all donors evaluated, 27% were found to be KIR3DL1-HIGH when considering the respective recipient HLA-Bw. Having multiple donors evaluated improved the likelihood of avoiding a KIR3DL1-HIGH donor: Among recipients with one donor evaluated, 27% had only KIR3DL1-HIGH donors available compared to 12% in recipients with 2-3 donors evaluated and 4% for recipients with >3 donors evaluated (P < 0.0001). Among all evaluated patients, 41% had both KIR3DL1-HIGH and KIR3DL1-LOW/NO donors available, indicating a potential selection based on KIR3DL1 was possible. Among 252 patients evaluated, 115 proceeded to allo HCT (48 with MDS, 67 with AML). The median age at transplant was 62 years (range 3.6-78). Donors were HLA matched in 105 transplants and were single loci mismatched in 10 transplants. Conditioning was myeloablative in 73 (11 with total body irradiation). GVHD prophylaxis was with ex vivo CD34+ selection in 65 patients and with tacrolimus/methotrexate in the remaining patients. The median follow-up in transplanted patients was 13.1 months (range 0.5-43.3 months). On univariate analysis, the 2-year disease-free survival was 64% (95% confidence interval: 54-76%) in those with KIR3DL1-LOW/NO donors versus 39% (22-68%) in recipients with KIR3DL1-HIGH donors (P = 0.05). The incidence of relapse was similar but favored patients with KIR3DL1-LOW/NO donors (26% [15-37%] versus 35% [13-57%], P = 0.5). 2-year overall survival was similar between those with KIR3DL1-LOW/NO versus KIR3DL1-HIGH donors (75% [65-86%] versus 69% [52-91%], P = 0.43). The time from the initiation of a formalized donor search to transplant did not differ between recipients with KIR3DL1-LOW/NO versus KIR3DL1-HIGH donors (median 81 v. 83 days, respectively, P = 0.97). Recipients with KIR3DL1-LOW/NO donors were CIBMTR Transplant Risk Score low = 53, intermediate = 6, and high = 33; whereas recipients of KIR3DL1-HIGH donors were low = 17, intermediate = 2, and high = 4 (P = 0.15). These results indicate that disease severity and transplant urgency did not influence whether a KIR3DL1-LOW/NO donor was able to be selected. In summary, these prospective data on 115 patients from a single center support improved outcomes in patients with AML and MDS undergoing unrelated donor allo HCT using a donor with low or absent KIR3DL1 inhibition. A multi-center, prospective study to evaluate the prospective use of HLA and KIR genotype based selection of URDs for patients undergoing allo HCT for AML is underway (NCT02450708). Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kernan: Gentium: Research Funding; The National Cancer Institute of the National Institutes of Health: Research Funding.

Maintenance Therapy with Low-Dose Subcutaneous 5-Azacitidine in Older Patients with AML in 1st Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1029-1029
Author(s):  
Jeffrey E Lancet ◽  
Rami S. Komrokji ◽  
HuiYi Lin ◽  
Carlos M. de Castro ◽  
David A. Rizzieri ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Older Patients ◽  
Research Funding ◽  
Low Dose ◽  
Disease Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free ◽  
Risk Categories

Abstract Abstract 1029 Poster Board I-51 Background: Elderly patients with AML have a poor outcome, with low complete response (CR) rates and durations of CR that are typically less than 1 year, highlighting the need for more effective post-remission therapy. 5-azacitidine (AZA) is a nucleoside analogue/DNA methyltransferase inhibitor approved for use in all FAB subtypes and risk categories of myelodysplastic syndromes (MDS). In higher-risk patients with MDS, including those with AML (former RAEB-T subtype), AZA improves overall survival and delays the time to leukemia transformation. We undertook a phase 2 pilot study of low-dose subcutaneous (SC) AZA in older adult patients with AML in 1st CR or CR with incomplete platelet recovery (CRp) following standard induction therapy. Methods: Study objectives included the following: 1) determine the one year disease-free survival in elderly patients with acute myeloid leukemia (AML) in first CR/ CRp treated with low-dose SC AZA as post-remission therapy. 2) determine safety and tolerability of SC AZA administered in the post-remission setting. 3) investigate the relationship between bone marrow genomic promoter methylation with 1-year disease-free survival. Eligibility included age ≥ 60 with AML in 1st CR/ CRp following 1-2 cycles of induction chemotherapy and 1-2 cycles of consolidation therapy, ECOG PS 0-2, adequate end-organ function. AZA was administered subcutaneously on 1 of 2 different dosing schedules: A) 50 mg/m2/d x 5d (d 1-5), or B) 50 mg/m2/d x 7d (d 1-5, 8-9). Cycles were repeated every 4 weeks, and up to 12 cycles. Results: As of August 2009, 16 patients have been enrolled on the study and 15 are currently evaluable. Nine patients received dosing schedule A and 6 received schedule B. Median age was 69 years (range 62-81); M/F was 13/2; baseline cytogenetic risk categories at initial diagnoses: poor (6), intermediate (8), and unknown/not done (1). Two of 15 patients had a history of antecedent MDS. Nine of 15 patients (60%) required 2 cycles of induction chemotherapy to achieve CR/CRp. The median time from achievement of CR/CRp to AZA initiation was 13.6 weeks (range 7 – 21.9 weeks). To date, the median number of AZA cycles received was 4, ;5 patients have received ≥ 6 cycles, 2 of whom have received the 12 planned cycles and another who remains on-study after 11 cycles. Median duration of CR/CRp was 54.8 weeks (95% CI: 28.1-96.4 weeks) estimated using the Kaplan-Meier method. Only 2 of 15 (13%) patients developed grade 3-4 non-hematologic adverse events (colitis, headache). Six of 15 (40%) patients developed reversible grade 3-4 neutropenia or thrombocytopenia, but only 3 required dose reduction. No patients discontinued AZA due to toxicity, and there were no deaths that occurred on-study. Criteria for early stoppage, based upon toxicity, have not been reached. Methylation array analyses are ongoing. SC AZA administered as maintenance therapy in older patients with AML in 1st CR/CRp appears feasible and safe. Extended treatment was possible in a high proportion of patients, with encouraging early signs of durable remissions. Accrual to this trial is ongoing and updated results will be presented. Disclosures: Lancet: Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau. de Castro:Celgene: Speakers Bureau. Rizzieri:Celgene: Research Funding, Speakers Bureau. List:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Genomic and Clinical Characterization of Adult Ph-Negative B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2821-2821
Author(s):  
Takahiko Yasuda ◽  
Dai Nishijima ◽  
Shinya Kojima ◽  
Masahito Kawazu ◽  
Toshihide Ueno ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Fusion Genes ◽  
Free Survival ◽  
Chromosome Translocations ◽  
Otsuka Pharmaceutical ◽  
Genetic Events ◽  
Disease Free

Abstract Although survival rate for children with Acute Lymphoblastic Leukemia (ALL) now exceeds about 90%, the outcome of adult patients with ALL is extremely poor. These differences might be attributed to the lack of insights into pathogenesis and clinical behavior of adult-ALL. Gross chromosomal alterations including chromosome translocations and aneuploidy are considered as early events in ALL and constitute disease subtypes. To identify chromosome translocations underlying adult with Ph-negative B-ALL, we performed RNA-seq analysis on RNA from individuals with B-ALL who had been treated on the Japan Adult Leukemia Study Group (JALSG) ALL202-O protocol (n = 149). We successfully identified chromosome translocations in 100 patients (67.1%). ZNF384 fusions were most frequently detected in 30 patients (20.1%) and they had wide range of fusion partners. DUX4- and MEF2D- fusions were also recurrently found in 7 (4.7%) and 9 (6.0%) patients, respectively. Chromosome translocations activating kinase and cytokine receptor were found in 25 patients (16.8%) with Ph-like gene expression profile. These alterations were almost completely mutually exclusive indicating these are likely to be primary genetic events. For simplicity, here we define (1) fusions involving ZNF384, DUX4, MEF2D, CEBP and PAX5 as well as TCF3-PBX1 and ETV6-RUNX1 as Transcription Factor fusions (TF fusions; 49% of patients), (2) fusions involving CRLF2, JAK2, PDGFRB, EPOR and ABL as Kinase/cytokine-receptor Activating fusions (KA fusions; 15%) and (3) non-recurrent fusions or the absence of fusions/aneuploidy as B-others (30%). First, we analyzed impact of the patient age on types of fusion genes, based of combined data of ALL202-O cohort, childhood B-ALL cohort (Lilljebjörn H, et al. 2016: n = 189) and ALL202-U cohort (Yasuda T, et al. 2016: n = 54). We found that incidence of ZNF384-, CEBP- fusions and B-others increases as patients age, whereas ETV6-RUNX1 and PAX5 fusions were more prevalent in younger patients, exhibiting negative association with age. DUX4 fusions and TF fusions were most prevalent in Adolescent and Young Adult (AYA) generation. JAK2-, PDGFRB-, EPOR- and KA- fusions were positively correlated with age. Next, we analyzed association between patient survival and types of fusions. In Japanese adult B-ALL cohort (ALL202-O and ALL202-U cohort), we observed ZNF384-, DUX4- fusions and TCF3-PBX1 were associated with better disease-free survival than B-others. Furthermore, when combined, MEF2D- (n = 14), CEBP- (n = 4), PAX5- fusions (n = 2) and ETV6-RUNX1 (n = 2) exhibited significantly better disease-free survival than B-others, indicating TF fusions were associated with an improved outcome. In contrast, KA fusions were associated with poorer disease-free survival than B-others. KMT2A fusions were comparable with B-others regarding to patient disease-free survival. These results allowed us to develop a prognostic schema to identify three distinct risk profile groups, based on types of fusion genes and cytogenetics (Table1); favorable-risk (5-year rate of disease-free survival 67.4%), intermediate-risk (5-year rate of disease-free survival 42.5%) and adverse-risk (5-year rate of disease-free survival 9.6%). This prognostic schema predicted the outcome independently of age, sex and methotrexate dose in multivariate analysis (p < 0.001). In conclusion, we promoted a better understanding of the genetic basis of adult B-ALL by focusing on fusion genes. Each chromosome translocations were closely associated with age. ZNF384-, KA fusions and B-others were characteristic for older-adult patients (40-65 years old) with B-ALL. We clearly demonstrated specific primary chromosome abnormalities are strong prognostic marker. Functional properties of primary genetic events (TF fusions vs. KA fusions) might be a key determinant of biological characteristics and clinical outcome. Disclosures Kiyoi: Novartis Pharma K.K.: Research Funding; Celgene Corporation: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; FUJIFILM Corporation: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Bristol-Myers Squibb: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Takeda Pharmaceutical Co., Ltd.: Research Funding; Sanofi K.K.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Phizer Japan Inc.: Research Funding; Eisai Co., Ltd.: Research Funding. Naoe:Astellas Pharma Inc.: Research Funding; Fujifilm Corporation: Patents & Royalties, Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Pfizer Japan Inc.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding.

Neoadjuvant Cisplatin Chemotherapy Before Chemoradiation: A Flawed Paradigm?

2007 ◽  
Vol 25 (33) ◽  
pp. 5281-5286 ◽  
Author(s):  
Rob Glynne-Jones ◽  
Peter Hoskin
Keyword(s):  
Local Treatment ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Free Survival ◽  
Palliative Intent ◽  
New Strategy ◽  
Meta Analyses ◽  
Disease Free ◽  
Selection Of Patients ◽  
Selection Of

Effective chemotherapy (CT) treatment of solid tumors emerged with the introduction of anthracyclines and platinum CT in the late 1970s, at first with palliative intent, and later extended into the adjuvant setting. High response rates led to the belief that systemic CT might improve locoregional control and also decrease the risk of distant metastases. A new strategy advocated cisplatin-based neoadjuvant CT (NACT) before definitive local treatment—either surgery or radiotherapy (RT). Response to NACT was viewed as a favorable prognostic sign, which allows the selection of patients most likely to benefit from RT or chemoradiotherapy (CRT). The aim of this discussion is to raise the debate regarding NACT in reducing metastases, improving local control and selecting out good responders for nonsurgical treatment in the following sites: head and neck, esophagus, cervix, anus, nasopharynx, and bladder; as well as non–small-cell lung cancer. NACT has almost invariably failed to deliver an improved outcome in terms of disease-free survival (DFS) or overall survival (OS) when delivered before RT or CRT in all solid tumor sites. The evidence that NACT may improve outcome in terms of DFS or OS is strongest when it is administered before surgical resection, but remains scant before RT or CRT. Taxane-containing regimens look more promising than does cisplatin NACT, but have not been shown to improve on concurrent CRT. Future meta-analyses should compare induction CT followed by RT and induction followed by CRT versus RT or CRT alone.

scholarly journals Triple Post-Transplant Cyclophosphamide (PTCY) Based Gvhd Prophylaxis for HLA Matched or HLA Haploidentical Transplants

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4881-4881
Author(s):  
Eugenio Galli ◽  
Elisabetta Metafuni ◽  
Sabrina Giammarco ◽  
Maria Assunta Limongiello ◽  
Idanna Innocenti ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Age Over 60 ◽  
Disease Free ◽  
Related Mortality

Abstract We report a retrospective analysis of 198 consecutive allogeneic stem cell transplant (HSCT) recipients, who received post transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mofetile as g raft-versus-host-disease (GVHD) prophylaxis. The donor was either HLA matched (n=78) (siblings -32- or unrelated -46) , or a haploidentical relative (HAPLO) (n=120). End points of the study were acute and chronic GVHD, transplant related mortality (TRM), relapse, disease free survival (DFS) and graft versus host and relapse free survival (GRFS). The two groups were comparable except for an older age (49 vs 56 years) in the haplo-HLA group. The diagnosis was mainly acute leukemia (57%), myelofibrosis (21%) or lymphoma (12%). Conditioning was myeloablative in 77% and 73% respectively (p=0.57). Acute GVHD grade II-IV developed in 10% of the HLA matched transplants vs 27% in the HAPLO group (p=0.005). The latter also had more moderate-to-severe cGVHD (4% vs 23%, p&lt;0.001). The cumulative incidence of transplant related mortality (TRM) at 1 year for the HLA matched vs HAPLO patients, was 10% vs 21% (p=0.04) (Fig.1) , with age over 60 years being the major negative predictor in multivariate analysis. Relapse at 1 year was 24% for HLA matched vs 10% for HAPLO transplants (p=0.051) (Fig.1). Disease free survival (DFS) at 1 year was 65% and 68% in matched and HAPLO patients, respectively (p=0.85) (Fig.1) and GRFS 55% vs 49% (p=0.18). In multivariate analysis, age over 60 years was the strongest predictor of DFS and GRFS (HR 1.73, p=0.03 and HR 1,65, p= 0.02). In conclusion: when using the same triple PTCY based GVHD prophylaxis, HLA matched grafts are associated with significantly less acute and chronic GvHD, if compared with HAPLO grafts. There is a trend for reduced TRM at 1 year, especially in chronic myelo-lymphoproliferative disorders, and a trend for increased relapse, resulting in identical disease free survival. Figure 1 Figure 1. Disclosures Laurenti: Gilead: Honoraria; Roche: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

Is Rituximab Needed With High Dose Chemotherapy and Autologous Stem Cell Transplant When Patients With Non-Hodgkin’s Lymphoma Have Been Exposed To It?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5552-5552
Author(s):  
Zartash Gul ◽  
Stephan Anderson ◽  
Stacey Slone ◽  
Saurabh Chhabra ◽  
Gregory Monohan ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Disease Free

Abstract Introduction The value of Rituximab with High dose chemotherapy and autologous stem cell transplant (auto-HCT) has been evaluated in some retrospective studies. It is noted that the addition Rituximab to auto-HCT results in significant improvement in overall (OS) and disease free survival (DFS). However, it is unclear that the addition of Rituximab with auto-HCT would result in significant benefit in patients who have received prior Rituximab based therapy. Methods We retrospectively evaluated twenty seven consecutive patients who had B cell non-Hodgkin's lymphoma (NHL) and underwent auto- HCT at Markey cancer center between January 2010 and December 2012. All patients received 375 mg/m2of Rituximab with chemotherapy. Rituximab was not administered with high dose chemotherapy (BEAM: BCNU, Etoposide, Cytarabine and Melphalan) prior to auto-HCT. All patients received GCSF starting day 5 after auto-HCT. Results There were 27 patients who underwent auto-HCT for NHL. Median age of the patients was 60 years (36-72 years). Nineteen patients were male and 8 patients were female. Fifteen patients were in complete remission (CR) and the rest were in partial remission (PR). Patients had: Diffuse large B cell lymphoma (DLBCL=11 patients): Mantle cell lymphoma (MCL=13 patients): follicular lymphoma (3 patients). Median CD 34 count of infused cells was 4.14 x 106 cell/kg (2.26- 9.45). Median time to neutrophil recovery was 11 days (9-14). Median lymphocyte count at day 30 after auto HCT was 1130 x 10 6/l (320- 5180). After a median follow up of 7.9 months (3.0- 32.4) eight patients had relapsed. Five patients who had relapsed had refractory disease before auto-HCT. Non -Relapse mortality (NRM) is shown in figure 1. Median overall survival and disease free survival were not reached. Seventy percent patients had not relapsed. We did not find any factors associated with relapse. Conclusion We performed a retrospective study to evaluate the impact of Rituximab with high dose chemotherapy and in patients with NHL. Review of literature showed that median 2 year and 5 year OS was 80% and 69% in patients who received Rituximab with auto HCT. Median 2 year DFS was 67%. In our study 70% patients were relapse free at a median follow up of 8 months. We would need a longer follow up to determine the efficacy of Rituximab with auto- HCT in patients with NHL who had prior exposure to Rituximab. Disclosures: Off Label Use: The use of Thymoglobulin® for GVHD prevention. Hayslip:Sanofi: Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Celgene: Research Funding.

scholarly journals Biomarkers for Predicting Long-Term Disease Control in Transplant-Ineligible Multiple Myeloma Patients: The Presence of an MGUS- like Signature Is the Most Relevant Predictor

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4503-4503
Author(s):  
Paula Rodriguez Otero ◽  
Maria-Victoria Mateos ◽  
Joaquin Martinez Lopez ◽  
Miguel-Teodoro Hernández ◽  
Enrique M. Ocio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Disease Control ◽  
Board Of Directors ◽  
Research Funding ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Disease Free

Abstract Introduction: Disease control at five years would be a desirable endpoint for elderly multiple myeloma (MM) patients; however, the percentage of cases reaching this objective as well as the biomarkers to predict it, are not well defined. Objective and design: In order to gain further insight about long-term disease control (>5 years progression-free) in elderly MM we have analyzed a homogeneous population of 435 newly-diagnosed transplant-ineligible (TNE) patients enrolled in two consecutive Spanish clinical trials (GEM2005MAS65, GEM2010MAS65), that included both proteasome inhibitors and immunomodulatory drugs. Results: Amongst the 435 patients included in this post-hoc study, only 18.8% remained alive and progression-free after five years of initiating treatment. Noteworthy, in these patients the overall survival (OS) rate at 10-years was 69.4%, as compared to 11.4% for those patients progressing during the first five years (p< 0.001). Baseline variables significantly associated with long-term progression free survival in the univariate analysis were younger age, ISS 1, R-ISS 1, hemoglobin ≥ 12g/dl, normal LDH, and standard-risk cytogenetic abnormalities and the presence of a monoclonal gammopathy of unknown significance (MGUS)-like immunophenotypic profile in the bone marrow. Complete responses (CR) and minimal residual disease (MRD) negativity were also associated with long-term progression free survival. In the multivariate analysis, an hemoglobin level ≥12g/dl (OR 2.61; 95% CI 1.47 - 4.61, p=0.001) and a MGUS-like immunophenotypic profile in the bone marrow (OR 3.33; 95% CI 1.30 - 8.54, p=0.002) were the two baseline variables significantly and independently associated with a higher probability of long-term disease-free survival. When the depth of response (including MRD) was included in the logistic regression model, Hb level ≥12g/dl (OR 2.18; p=0.010) and the MGUS-like signature (OR 4.99, p<0.001) retained their independent predictive value along with the achievement of MRD-negativity (OR 4.09, p<0.001). Focusing on the 24 patients with an MGUS-like signature (based on the automated immunophenotyping analysis of the relative frequency of BM plasma cells (PCs) plus the percentage of clonal and normal PCs within the whole BM PC compartment), 50% percent of these patients displayed a long-term disease-free survival, as compared to only 17.5% of the remaining MM patients. The median OS for patients with MGUS-like signature was 90.2 months as compared to 62.6 for the MM-like patients. Most MGUS-like patients (90.5%) achieved a favorable response (10 complete response (CR) and 9 very good partial response (VGPR)). No differences in outcome were observed between VGPR and CR cases (p-value for OS 0.87) among MGUS-like patients. Conclusions: This study revealed that despite the usage of former novel agents, the probability of disease control at five years is still restricted to a small fraction (18.8%) of transplant-ineligible patients that achieve remarkable rates of long-term OS. Here, we identify that the combination of three biomarkers (normal Hb, MGUS-Like signature and MRD negativity) can help todefine elderly MM patients achieving long-term disease control. Our results highlight the presence of an MGUS-like signature in the bone marrow at diagnoses as the most powerful predictor for long-term disease free survival, and could be incorporated in clinical practice in order toimprove the prognostic information given to our patients. Disclosures Rodriguez Otero: Clínica Universidad de Navarra: Employment; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Bristol Myers Squibb: Research Funding. Mateos:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Martinez Lopez:Janssen: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau. Ocio:Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy; Pharmamar: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy; Novartis: Consultancy, Honoraria; Sanofi: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Mundipharma: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Array Pharmaceuticals: Research Funding. Puig:Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Oriol:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bladé:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Lahuerta:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. San-Miguel:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; BMS: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Roche: Honoraria.

scholarly journals Clinical outcomes and surgical preferences for breast-conserving surgery and mastectomy: a propensity score-matched analysis

2019 ◽  
Vol 13 (3) ◽  
pp. 95-100
Author(s):  
Mawin Vongsaisuwon ◽  
Krit Pongpirul ◽  
Kris Chatamara
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Propensity Score ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Conserving Surgery ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Disease Free ◽  
Selection Of

Abstract Background While numerous randomized controlled trials have demonstrated long-term survival rates for patients with early-stage breast cancer treated with breast-conserving surgery (BCS) comparable to mastectomy, the latter remains the most prevalent surgical option to treat early-stage breast cancer in Thailand. Objectives To investigate the potential determinants affecting the decision on selecting BCS or mastectomy for the treatment of early-stage breast cancer and to compare the disease-free survival and overall survival between the treatments using a propensity score-matched analysis. Methods Patients diagnosed nonmetastatic breast cancer at the Queen Sirikit Breast Cancer Center from January 2006 to December 2015, were retrospectively identified and grouped intro patients who received BCS or mastectomy. After propensity score matching, 356 BCS and 209 mastectomy patients were identified, and statistical analysis was conducted to determine treatment selection factors and compare disease-free and overall survival. Results Disease-free survival and overall survival in months comparing BCS and mastectomy were not statistically different with P values of 0.11 and 0.77, respectively. Determinants of treatment selection found that younger age, surgeon preference, smaller tumor size, and lower tumor grade were statistically significant factors in the selection of BCS over mastectomy. The majority of surgeons had a preference for one treatment over the other (P < 0.001). Conclusion The outcome of BCS is comparable to mastectomy in early-stage breast cancer patients. Key determinants affecting the selection of treatment were identified to be patient age, characteristics of the tumor, and surgeon’s preference.

Sign in / Sign up

Export Citation Format

Share Document