Multiple Myeloma Multicenter Registry in Colombia: The Impact of Autologous Stem Transplantation on Overall and Disease-Free Survival

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Virginia Abello ◽  
Claudia Lucia Sossa ◽  
Henry Idrobo ◽  
Guillermo Quintero ◽  
William Mantilla ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Entire Group ◽  
Hematologic Neoplasms ◽  
First Line ◽  
Free Survival ◽  
The Impact

Aim: RENEHOC (Registro Epidemiológico de Neoplasias Hematológicas en Colombia) is a multicenter clinical quality database established in January 2018. The primary aim of the database is to provide local information on diagnosis and treatment of Multiple Myeloma (MM) and other hematologic neoplasms; this is key to show authorities the improvements that must be made to achieve better outcomes for Colombian patients and pose research questions relevant to our population. The aim of this report is to analyze variables related to event free survival (EFS) and overall survival (OS) in MM Colombian patients. Study population: An ambispective registry of adult MM patients, treated in approved centers over the last 10 years in Colombia. As of July 2020, 890 patients have been registered. Descriptive statistics were used for patient's demographic and clinical characteristics. The Kaplan-Meier method was used to assess DFS and OS. Hazard Ratios (HR) using Cox proportional hazards regression modeling was estimated. <65 yrs. patients were considered transplant eligible (TE) and older than 65 yrs. transplant ineligible (TI). Results: Data from 890 MM patients were reviewed. Median age at diagnosis was 66.8 (SD 11.17) years (TE 57 yrs., SD 6.71; TI 74.8 yrs., SD 6.87); 398 (57%) were TE; 52.9% were male. At diagnosis median hemoglobin was 10.1 (SD 2.5), 242 (27.2%) had renal failure, and 379 (42.6%) pathological fractures. IgG was the most common M component (n=328, 36.8%). Most patients were in an advanced stage by Durie Salmon at diagnosis (DS IIIA or IIIB: n=523, 77.4%), and had high risk ISS (ISS 1: n=128, 20.6%; ISS 2: n=180, 29.0%; ISS 3: n=312, 50.3%; NA n=270). Only 17,9% (n=160) had cytogenetic prognostic characterization. There were not significant differences in clinical characteristics at diagnosis between TE and TI patients. The most common induction regimen for TE were Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) (n=190, 49%) and Bortezomib-Thalidomide-Dexamethasone (VTD) (n=103, 27%). For TI patients, most common regimens in first line were CyBorD (n=111, 245), VTD (n=90, 19%) and Bortezomib-Dexamethasone (Vd) (n=84, 18%). 69% TE and 59% TI patients had partial response or better after first line. 41% of TE patients actually received an Autologous Stem Cell Transplantation (ASCT) after 1 line. 19% of TI patients received an ASCT. Of note, in 78% of patients considered to have indication not taken to transplant, administrative barriers of access are reported. Mean follow-up for the entire group was 28.35 months (SD 29.27, CI 26.41-30.29). The median DFS was 62 months being significantly longer in TE patients (74 vs 53 months for TI, p=0.0002), estimated 5 years DFS 52% (TE 56% vs 46% for TI). Median OS was 88 months (Not reached for TE vs 75 moths for TI, p=0.0001), estimated 5 years OS 62% (TE 70% vs 56% for TI). Univariate analysis showed ISS at diagnosis, age and ASCT were significantly related to OS. On multivariate analysis ISS 3 (HR 1.89; p=0.004; CI 1.22-2.93) at diagnosis and ASCT (HR 0.26, p=0.0001, CI (0.18-0.39) were the only factors significantly associated with OS. 5 yrs. OS for patients that received ASCT was 80% in comparison to 48% if not done. Conclusion: At this timepoint data from RENEHOC is still limited, however, the potential of this growing registry is evident; until now little information about hematologic neoplasms in Colombia was available, this effort allows us to know the reality of our patients and plan relevant trials in our settings. We report here characteristic of a large cohort of MM patients in Colombia. OS and DFS are comparable with what have been published for similar patients in other latitudes. Consolidation with ASCT was the most important factor affecting prognosis in this cohort; the low transplant rate has to be addressed to improve outcomes for myeloma patients in Colombia. Figure Disclosures Abello: Abbvie: Consultancy, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Honoraria. Sossa:Takeda: Honoraria; Novo: Honoraria; Astellas: Honoraria; Roche: Honoraria. Idrobo:Takeda: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Henao-Uribe:Alexion: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Takeda: Consultancy, Speakers Bureau.

Multi-modality management of extraosseous Ewing sarcoma: 10-year experience from a tertiary care centre

2020 ◽  
pp. 1-7
Author(s):  
Arvind Sathyamurthy ◽  
Ashish Singh ◽  
Tarun Jose ◽  
Patricia Sebastian ◽  
Rajesh Balakrishnan ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Disease Free Survival ◽  
Molecular Techniques ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
The Impact ◽  
Extraosseous Ewing Sarcoma ◽  
Disease Free

Abstract Aim: To analyse the presentation, diagnosis and patterns of care of extraosseous Ewing sarcoma treated at our institution between 2008 and 2018. Methods: Electronic medical records of extraosseous Ewing sarcoma patients treated at our institution between January 2008 and April 2018 were reviewed. Kaplan–Meier curves were plotted to assess the overall and disease-free survival with 95% confidence intervals. A univariate analysis was carried out to assess the impact of variables such as surgical excision, completeness of surgery, completeness of chemotherapy and addition of radiation therapy on the survivorship. Results: The records of 65 patients treated at our institution were available for review. The mean age was 26·4 years. The most frequent sites of extraosseous Ewing tumour were kidney—9/65 (13·8%) and brain—10/65 (15·4%). Sixteen (24·6%) patients presented with inoperable/metastatic disease at diagnosis. The other 49 (75·4%) had localised disease at presentation. The median overall survival of the 49 non-metastatic patients was 46 months, and the disease-free survival was 45 months. Conclusion: Extraosseous Ewing sarcoma is a rare and aggressive tumour diagnosed by molecular techniques. Multi-modality treatment including surgical resection with wide margins, adjuvant radiation when indicated and completion of systemic chemotherapy results in optimum outcomes.

Growth Differentation Factor 15 Is a Survival Factor for multiple myeloma cells and its plasma Concentration In Patients Is Related to Reduced Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 614-614
Author(s):  
Jill Corre ◽  
Elodie Labat ◽  
Nicolas Espagnolle ◽  
Hervé Avet-Loiseau ◽  
Murielle Roussel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Concentration ◽  
Cell Line ◽  
Healthy Subjects ◽  
Univariate Analysis ◽  
Culture Conditions ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
The Impact

Abstract Abstract 614 We previously reported that bone marrow mesenchymal stem cells (BMMSCs) from newly diagnosed multiple myeloma (MM) patients were abnormal. In particular, we showed that Growth Differentiation 15 (GDF15) expression was higher in MM BMMSCs than in normal BMMSCs. GDF15 is a divergent member of the human TGFβ superfamily. GDF15 overexpression has been described in numerous malignancies and its concentration is increased in the serum of patients with glioma, prostate, colorectal or pancreatic cancers. Contradictory data prevent to understand clearly GDF15 implication in pathophysiology of tumors. Furthermore, GDF15 has never been studied in haematological malignancies. Our first objective was thus to determine the effect of human recombinant GDF15 (rGDF15) on MOLP-6 stroma-dependent cell line and MM1.S stroma-independent cell line under serum free culture conditions. rGDF15 could significantly increase cell survival in MOLP-6 but not in MM1.S. Interestingly, rGDF15 was able to induce Akt phosphorylation on Threonine 308 in MOLP-6 and primary MM cells but not in MM1.S cells. Furthermore, pre-treatment of MOLP-6 with Akt pharmacologic inhibitor abrogated the prosurvival effect of GDF15, suggesting an Akt-dependent mechanism. In the same culture conditions, we observed that rGDF15 could abrogate toxicity of drugs classically used in MM treatment (melphalan, bortezomid and lenalidomide) for both cell lines MOLP-6 and MM1.S, suggesting that this cytoprotective effect may be Akt-independent. Because of the in vitro effects of GDF15, our second objective was to determine whether the plasma concentration of GDF15 (pGDF15) in patients with MM may be indicative of the seriousness of the disease or correlate with the response to the treatment. Thus, we investigated the pGDF15 in 131 patients with newly diagnosed MM and 13 healthy subjects. We first found that it was significantly higher for patients with MM (0.90±1.10 ng/mL) than for healthy subjects (0.25±0.08 ng/mL) (P< .001). In patients with MM, pGDF15 correlated with the main prognostic factor of the disease (i.e. International Staging System, b2 microglobulin level, presence or absence of deletion of chromosome 13, and bone status). For the 81 patients with high pGDF15 level (≥ 0.50 ng/mL), the probabilities of event-free and overall survival 30 months after diagnosis were 50% and 75%. For the 50 patients with low pGDF15 level (< 0.5 ng/mL), the probabilities were 80% and 97% (P< .0045 and P< .013, respectively). However, we did not find a clear relationship between pGDF15 and response to treatment. We analysed the impact of prognostic factors on event-free survival for the 131 patients with MM. On univariate analysis, event-free survival was significantly related to age (P= .003), b2-microglobulin level (P= .02) and pGDF-15 level (P= .003). On multivariate analysis, event-free survival was significantly related to age (P= .001) and pGDF15 level (P= .04). Our study demonstrates that GDF15 is a survival and cytoprotective factor for MM cells and that pGDF15 is related to initial parameters of the disease and survival, which specifically implicates the MM microenvironment in the pathophysiology and the prognosis of the disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunophenotypic Response After Allografting In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3371-3371 ◽  
Author(s):  
Luisa Giaccone ◽  
Lucia Brunello ◽  
Roberto Passera ◽  
Moreno Festuccia ◽  
Milena Gilestro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
First Line ◽  
Significant Difference ◽  
The Impact

Abstract Background Minimal residual disease (MRD) by multiparameter flow-cytometry recently showed a promising role in predicting outcomes in patients with multiple myeloma. However, data on immunophenotypic response (IR) after allografting are lacking. Aim To evaluate the impact of IR and compare it to conventional complete remission (CR) following allografting in myeloma patients. Methods Sixty-six consecutive patients, median age 54 years (35-66), who underwent an allograft between January 2000 and December 2011 with a follow-up of at least 3 months were included. Disease response was evaluated by serum and urine electrophoresis, and bone marrow aspirate at baseline, 3, 6, 12, 18, 24 months after transplant and yearly thereafter. Skeletal survey or MRI were performed yearly or as clinically indicated (overt relapse or complaints of bone pain). Bone marrow aspirates had to contain at least 13000 cells/µL for flow-cytometry studies and IR was defined as absence of monoclonal plasma-cells detected by 4 or 6-colour staining with the following antibodies: CD38, CD138, CD56, CD19, CD45, cyKappa, cyLambda. CR was defined according to standard criteria (Durie et al, Leukemia 2006; 20:1467-73). Results Conditioning regimen was non-myeloablative 2Gy TBI-based in 55 patients, reduced intensity (fludarabine-melphalan-based) in 10 and myeloablative in 1 patient. Post-grafting immunosuppression consisted of cyclosporine with mycophenolate mofetil or methotrexate. Donors were HLA identical siblings in 58 patients and unrelated in 8. Only 1 patient received bone marrow as source of stem cells. Thirty-five/66 (53%) received the allograft as part of the first line treatment, whereas the remaining 31/66, (47%) were transplanted at relapse. At the time of transplant, 5/66 were both in IR and CR, 16 were only in IR and 4 patients were only in clinical CR. All 21 patients in IR at the time of transplant maintained it, while 26/45 (58%) entered IR after the allograft. Among patients surviving at least 3 months, overall treatment related mortality was 10.6% at 3 years. After a median follow-up of 69 months (range 19-147), the incidence of acute and chronic graft-versus-host disease was 45.6% and 49.3% without significant difference between responsive and non-responsive patients. At follow-up, overall, 24 patients achieved CR and IR (CR/IR group), 21 achieved IR but not CR because of persistence of urine/serum M-component (noCR/IR group), and 21 did not achieve either CR or IR (noCR/noIR group). Interestingly, none achieved CR without IR. Median overall survival (OS) and event-free survival (EFS) in patients who achieved IR were 96 and 55 months versus 36 and 7 months in those who did not (p<0.001). Median OS and EFS were not reached and 59 months in the CR/IR group, 77 and 15 months in the noCR/IR, and 30 and 5 months in the noCR/noIR respectively (p<0.001 for both EFS and OS-fig.1). In univariate analysis, being in the CR/IR group was the only significant predictor for prolonged OS and EFS (p<0.001). Of note, cumulative incidence of extra-medullary disease at first relapse after the allograft was 4% in the CR/IR, 32% in the noCR/IR and 15% in the noCR/noIR groups respectively (p<0.001). Receiving the allograft as first line therapy or later during the disease course did not significantly impact on OS and EFS. Conclusion The achievement of IR confers a favorable impact on OS and EFS after allografting. A higher incidence of extra-medullary in the noCR/IR group (some 30% of our patient cohort) may suggest that myeloma cells escape immune control outside the bone marrow. In this group, imaging studies such as positron emission tomography may clinically be indicated during follow-up to detect early relapse. Disclosures: No relevant conflicts of interest to declare.

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1845-1845 ◽  
Author(s):  
Victor H Jimenez-Zepeda ◽  
Christopher P. Venner ◽  
Andrew Belch ◽  
Irwindeep Sandhu ◽  
Tatiana Nikitina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Regimen ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
P Value ◽  
Similar Response ◽  
Free Survival

Abstract Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods: The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: Ninety-one patients have received CyBorD and 56 have received LD. Clinical characteristics are shown in Table 1. At the time of analysis, 64 and 32 patients in the CyBorD and LD are alive of which 10 and 11, respectively, have progressed, ORR and VGPR rates were 85.7% and 56% for patients treated with CyBorD, and 83.9% and 64% for LD respectively (p=0.3). Estimated median OS was 40 months for CyBorD compared to 66 months for LD (p=0.156). In addition, median PFS was longer for LD patients compared to CyBorD (26 months vs 16.4 months, p=0.018). The rate of treatment discontinuation was similar between both groups (8.7% vs 10%, p=0.3). In Conclusion: CyBorD and LD appeared to be effective treatment options for NTE myeloma patients with similar response rates. Recognizing the limitations of a retrospective series, it is interesting to note a longer PFS and a trend towards better PFS in the LD group, however, longer follow-up and prospective validation is still required. Table 1. Clinical Characteristics Characteristic CyBorD, n=91 LD, n=56 P value Age (median) 73.9 73.6 0.2 GenderMaleFemale 57 (62.6%)34 (37.4%) 34 (60.7%)22 (39.3%) 0.8 B2microglobulin (µmol/L) 4.9 4.89 0.4 Albumin (g/L) 35 36 0.7 Stage IStage IIStage III 17.7%35.4%46.9% 23.5%37.2%39.3% 0.6 BMPC (%) 32 37.5 0.6 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 501018113 26179010 0.068 Response rateORRCR/nCRVGPRPR 85.7%23%31.8%30.7 83.9%28%37.5%17.8% 0.3 Ab: BMPC: Bone marrow plasma cell Figure 1. Overall Survival according to treatment regimen Figure 1. Overall Survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Venner:J&J: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria. Sandhu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan:Celgene: Honoraria; Jansen: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia

2018 ◽  
Vol 07 (04) ◽  
pp. 263-266 ◽  
Author(s):  
Rachana Chennamaneni ◽  
Sadashivudu Gundeti ◽  
Meher Lakshmi Konatam ◽  
Stalin Bala ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Entire Group ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Secondary Objective ◽  
Normal Cytogenetics ◽  
The Impact

Abstract Context: In acute lymphoblastic leukemia (ALL), the most important prognostic factors are age, leukocyte count at presentation, immunophenotype, and cytogenetic abnormalities. The cytogenetic abnormalities are associated with distinct immunologic phenotypes of ALL and characteristic outcomes. Aims: The present study was primarily aimed at analyzing the impact of cytogenetics on postinduction responses and event-free survival (EFS) in pediatric patients with ALL. The secondary objective was to study the overall survival (OS). Subjects and Methods: A total of 240 patients with age <18 years and diagnosed with ALL between January 2011 and June 2016 were retrospectively analyzed. Cytogenetics was evaluated with conventional karyotyping or reverse transcriptase polymerase chain reaction. Based on cytogenetic abnormalities, the patients were grouped into five categories, and the outcomes were analyzed. Results: Of the 240 patients, 125 (52%) patients had evaluable cytogenetics. Of these, 77 (61.6%) patients had normal cytogenetics, 19 (15.2%) had t(9;22) translocation, 10 (8%) had unfavorable cytogenetics which included t(9;11), hypodiploidy, and complex karyotype, 10 (8%) had favorable cytogenetics which included t(12;21), t(1;19), and high hyperdiploidy, 9 (7.2%) had miscellaneous cytogenetics. Seventy-one percent of patients were treated with MCP 841 protocol, while 29% of patients received BFM-ALL 95 protocol. The 3-year EFS and OS of the entire group were 52% and 58%, respectively. On univariate analysis, EFS and OS were significantly lower in t(9;22) compared to normal cytogenetics (P = 0.033 and P = 0.0253, respectively) and were not significant for other subgroups compared to normal cytogenetics. On multivariate analysis, EFS was significantly lower for t(9;22) and unfavorable subgroups. Conclusions: Cytogenetics plays an important role in the molecular characterization of ALL defining the prognostic subgroups. Patients with unfavorable cytogenetics and with t(9;22) have poorer outcomes.

scholarly journals Bortezomib and High Dose Melphalan (Bor-HDM) Compared to HDM Conditioning for the Treatment of Transplant Eligible Multiple Myeloma: Report from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3189-3189
Author(s):  
Victor H Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Marcia Culham ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Melphalan ◽  
The Impact

Abstract Introduction Preclinical and clinical data suggest that bortezomib in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the quality of response for MM patients undergoing auto-SCT. In the present study, we aimed to assess the impact of Bor-HDM conditioning on ORR, and MRD negativity for MM patients undergoing single auto-SCT at our Institution. Methods All consecutive patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to 06/2015 using Bor-HDM or HDM as conditioning regimen were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. MRD negativity was assessed by multiparameter flow cytometry. All patients received induction chemotherapy before undergoing auto-SCT. Bortezomib was administered intravenously at 1-1.3 mg/m2 on days −5, −2, 1, and 4, while melphalan was given at 200 mg/m2 on day −1. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results Two-hundred and fifty-eight consecutive patients receiving Bor-HDM or HDM alone were evaluated. A total of 85 patients received Bor-HDM conditioning and 173 received HDM. Clinical characteristics and chemotherapy induction regimens are listed in Table 1. At day-100 post auto-SCT a ³VGPR was seen in 83.3% in the Bor-HDM group compared to 67.6% for HDM patients. The CR/nCR rate was higher in the Bor-HDM group (47.6% vs 23.6%) as well as MRD negativity assessed by flow cytometry (30.9% vs 9.7%, p=0.0001). Median OS in the Bor-HDM group was NR compared to 95 months for HDM alone (p=0.572), while median PFS was 39.3 months for Bor-HDM compared to 27 months for HDM (p=0.1). Median OS was shorter in the HR cytogenetic group regardless of the type of conditioning regimen employed (39 months vs NR for SR cytogenetics). In addition, patients who achieved MRD negativity, exhibited a longer OS (NR vs 78 months, p=0.007). Transplant-related mortality (TRM) was similar between both groups (p0.5). In conclusion, Bor-HDM is a safe and efficacious conditioning regimen able to increase the nCR/CR and MRD negativity rates compared to HDM. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed, with special view on the high-risk MM patients where response rates are good but sustainability remains an issue. Table 1. Clinical Characteristics Characteristic Bor/HDM, N=85 HDM alone, N=173 Age (median) 58 59 GenderMaleFemale 51 (60%)34 (40%) 113 (65.3%)60 (34.7%) Hb (g/L) 112 117 Calcium (µmol/L) 2.25 2.29 Creatinine (µmol/L) 85 80 B2microglobulin (µmol/L) 3.3 2.79 Albumin (g/L) 31 35 Stage IStage IIStage III 154723 617333 M-spike (g/L) 34 30 LDH (IU/L) 194 180 BMPC (%) 40 33 Heavy chain:IgGIgAIgDFLC onlyBiclonalIgM 491811511 1142403210 Light chain:KappaLambdaBiclonal 50351 124471 High riskStandard risk 2263 36135 InductionCyBorDVDDexamethasoneRVD 4524016 16544315 Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Disclosures Jimenez-Zepeda: Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding.

Very Good Partial Response and Complete Response Predict Superior Overall Survival and Progression Free Survival After Single Autologous Stem Cell Transplant in Patients with Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4111-4111
Author(s):  
Victor H Jimenez-Zepeda ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
Christine Chen ◽  
Andrew Winter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact

Abstract Abstract 4111 In multiple myeloma (MM), the impact of complete response (CR) and very good partial response (VGPR) achievement has been shown mostly after introduction of high dose therapy (HDT) supported by autologous stem cell transplant (ASCT). Recently, the IFM group reported the impact of achievement of CR and VGPR in double ASCT. The purpose of this study is to confirm the prognostic value of CR/VGPR in a large group of patients treated with single ASCT. Methods All consecutive patients who underwent single ASCT at Princess Margaret Hospital between January 2000 and December 2007 were evaluated. Patients were mobilized with cyclophosphamide and G-CSF and majority were conditioned with melphalan 200mg/m2. Response to therapy was assessed according to the IMWC including VGPR. Progression Free Survival (PFS) and Overall Survival (OS) were measured from transplant date to the date of death or last follow-up. OS and DFS were analyzed using the Kaplan-Meier Method. The Cox proportional hazard model was used to assess CR and VGPR and some other prognostic markers at presentation such as age, B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP> 20mg/L, albumin<35g/L and creatinine > 200 μmol/L. All p-values were 2-sided and statistically significant if <0.05. Results 788 patients were identified for the study; their median age was 56 years (30–73). Patient's characteristics are listed in Table 1. Response was assessed at day 100 after ASCT and showed a CR of 6%, PR of 37.5%, and VGPR of 53% (Overall Response rate of 95.5%). Median OS and PFS for the group were 77.43 months and 20.63 months respectively. The median OS and PFS were significantly better for patients who achieved CR/VGPR, 104.5 months versus 51.7 months, and 26.3 months versus 13.53 months respectively. With a median follow-up of 44 months there is no significant difference in OS for those patients who achieved VGPR/CR after induction therapy with novel agents. However, PFS is better in those patients receiving novel agents who achieved VGPR/CR (Median PFS of 24.63months versus 12.4 months respectively (p=0.01). Multivariate analysis shows CR/VGPR as an independent prognostic factor for OS and PFS (Fig 1 and 2). B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP > 20mg/L, albumin<35g/L and creatinine > 200 μmol/L failed to be important factor for survival in the multivariate analysis. Our data suggests that VGPR/CR is clearly important in the pre-novel agents era and for the smaller group of patients who had novel agents induction there is a benefit in PFS and with a longer follow-up perhaps in OS. In conclusion, VGPR/CR remains a simple and powerful indicator in the context of single ASCT and should be considered a relevant objective for MM treatment. Table 1. Clinical characteristics of patients with Multiple Myeloma undergoing single ASCT Clinical characteristic N=788 Median Range % Age (years) 58 31–74 Male 59.4% Female 40.6% Hemoglobin (g/L) 114 54–180 Creatinine (μmol/L) 107 28–1409 B2-microglobulin ((μmol/L) (N=718) 508 260–7270 Albumin (g/L) (N=650) 38 23–54 IgG 51.1% IgA 31.3% IgM 0.4% IgD 0.7% Biclonal 9.9% Not Detected 6.6 Kappa 59.4% Lambda 32.9% Biclonal 2% Not Detected 5.7% Calcium (μmol/L) 2.29 1.62–4.66 LDH (IU/L) (N=754) 235 50–1470 Induction Treatment: 52.2% VAD 22.8% Dexamethasone 6.3% TD 2.3% CP 3.8% DPACE/DTPACE 1.7% DVD 8% CyBORD 2% VD Ab: VAD: Vincristine, Adriamycin and dexamethasone, TD: Thalidomide and Dexamethasone; CP: Cyclophosphamide and Prednisone, DVD: Doxil, Velcade and Dexamethasone, CyBORD: Cyclophosphamide, Bortezomib and Dexamethasone and VD: Valcade and Dexamethasone Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

scholarly journals Prospective Evaluation of Sarcopenia in Head and Neck Cancer Patients Treated with Radiotherapy or Radiochemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 753
Author(s):  
Sébastien Thureau ◽  
Lucie Lebret ◽  
Justine Lequesne ◽  
Marine Cabourg ◽  
Simon Dandoy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Nutritional Support ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Curative Intent ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Highlights: Sarcopenia is frequent in patients treated with radiation therapy (RT) or radiochemotherapy (RTCT) for head and neck squamous cell carcinomas. Sarcopenia is associated with poor disease-free survival and overall survival outcomes. Sarcopenia is not associated with a higher rate of treatment-related toxicity. Background: Sarcopenia occurs frequently with the diagnosis of head and neck squamous cell carcinoma (HNSCC). We aimed to assess the impact of sarcopenia on survival among HNSCC patients treated with radiotherapy (RT) or radiochemotherapy (RTCT). Methods: Patients treated between 2014 and 2018 by RT or RTCT with curative intent were prospectively included (NCT02900963). Optimal nutritional support follow-up, including weekly consultation with a dietician and an oncologist and daily weight monitoring, was performed. Sarcopenia was determined by measuring the skeletal muscles at the L3 vertebra on the planning CT scan for radiotherapy. For each treatment group (RT or RTCT), we assessed the prognostic value of sarcopenia for disease-free survival (DFS) and overall survival (OS) and its impact on treatment-related toxicity. Results: Two hundred forty-three HNSCC patients were included: 116 were treated by RT and 127 were treated by RTCT. Before radiotherapy, eight (3.3%) patients were considered malnourished according to albumin, whereas 88 (36.7%) patients were sarcopenic. Overall, sarcopenia was associated with OS and DFS in a multivariate analysis (HR 1.9 [1.1–3.25] and 1.7 [1.06–2.71], respectively). It was similar for patients treated with RT (HR 2.49 [1.26–4.9] for DFS and 2.24 [1.03–4.86] for OS), whereas for patients treated with RTCT sarcopenia was significantly associated with OS and DFS in univariate analysis only. Sarcopenia was not related to higher treatment-related toxicity. Conclusions: Pretherapeutic sarcopenia remains frequent and predicts OS and DFS for non-frail patients treated with curative intent and adequate nutritional support.

scholarly journals Racial Disparity in Patients with Multiple Myeloma Are Blunted in the Era Novel Therapies

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2525-2525
Author(s):  
Leon Bernal-Mizrachi ◽  
Ajay K Nooka ◽  
Chandra Pooja ◽  
Monica S Chatwal ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Univariate Analysis ◽  
Novel Agents ◽  
Factors Associated ◽  
Indolent Disease ◽  
The Impact ◽  
White Patients

Abstract Background: Multiple myeloma is the most common hematological malignancy among african americans (AA). Prior studies have shown conflicting results for outcomes based upon ethnicity following autologous stem cell transplantation (ASCT). However, much of this data is older, and predates the use of novel agents such as bortezomib (V), lenalidomide (R) and thalidomide (T). Methodology: We performed a retrospective analysis of 292 patients (147 AA and 145 Caucasian) treated with novel agents (proteasome inhibitors or immune modulators) and ASCT from 2006 to 2012 at the Winship Cancer Institute of Emory University to evaluate the impact of ethnicity on outcomes. Results: Baseline characteristics such as stage (International Staging System, ISS), presence of lytic lesions or plasmacytomas, immunoglobulin subtype, and cytogenetic risk category at presentation, were comparable between AA and white patients. Among AA, 112 (76.19%) patients received bortezomib containing regimens (VRD: 34.8%, VTD: 22.3%, VDTPACE:11%, VDD:10%, VD:19% and others bortezomib regimens 8%), 54 (36.7%) patients received lenalidomide (VRD: 34.8% or RD: 11.6%) and 72 (49%) patients received thalidomide (VTD: 22.3% or TD: 11.6%). In white patients 113 (77.93%) received bortezomib containing regimens (VRD: 33.1%, VTD: 17.2%, VDTPACE:9.6%, VDD: 1.4% and VD:11.7% and other bortezomib regimens 1.3%), 69 (47.6%) patients received lenalidomide containing regimens (VRD:33.1% and RD:11%) and 62 (42.8%) patients received thalidomide containing regimens (VTD: 17.2% or TD: 15%). A higher percentage of patients in the white cohort carried the antecedent diagnosis of monoclonal gammopathy in white patients (AA:0 vs white: 4.8%, p=0.007), and as expected, AA patients presented at a younger age when compared with whites (mean age of 55 vs 59 years, respectively, p<0.001). The overall response rate (ORR) of induction in the entire population was 86%, with an >VGPR of 58.8%. No difference was identified in pre-transplant ORR and >VGPR between AA (87.9% and 25.9%, respectively) and white patients (81.54% and 22.4%, respectively, p>0.1). Similarly, the ORR and >VGPR 100 days after transplantation was comparable between both ethnic groups (AA: OR:90.74% and >VGPR:74.07% vs white OR:90.65% and >VGPR: 77.57%, p>0.1). The depth of response after ASCT improved similarly in both groups (AA: 57.3% vs white: 67.7%, p=0.1). When the overall survival and progression free survival where evaluated, we found no significant differences between both cohorts. Factors associated with longer PFS in the population studied include AA race and the introduction of lenalidomide in the induction regimen. In AA patients univariate analysis identified early stage at presentation, indolent disease (prolong time from diagnosis to transplant), optimal pre-transplant response, and pre-transplant use of lenalidomide (HR:0.38 (0.18-0.8), p=0.01) as factors that potentially prolong PFS. Multivariate analysis identified the use of lenalidomide, as part of the pretransplant regimen, to reduce the risk of relapse (HR:0.38 (0.18-0.8), p=0.01) compared to bortezomib use (HR: 5.3 (2.11-11.98), p<0.001). In white patients, univariate and multivariate analysis identified that IgG and kappa light chain MM and indolent disease were factors associated with longer PFS, while history of plasma cell leukemia was related to shorter PFS. In conclusion, our results showed that novel agents have improved the response rate of both ethnic populations. From our preliminary analysis, it appears the PFS is longer among AA patients, suggesting a potential difference in MM biology of this patient population. Disclosures Lonial: Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

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