Age Related Outcomes for Multiple Myeloma Patients Following Autologous Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3968-3968 ◽  
Author(s):  
Justin LaPorte ◽  
Stacey Brown ◽  
Xu Zhang ◽  
Asad Bashey ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Age Groups ◽  
Disease Status ◽  
The United States ◽  
Disease Stage ◽  
Age Group ◽  
Post Transplant

Abstract Multiple myeloma is the second most common hematological malignancy in the United States. The risk of developing multiple myeloma increases with age; with approximately 85% of patients are over age 55 and 62% over age 65. Through improved supportive care, increased access to hematopoietic stem cell transplantation, and introduction of new biologic agents, survival has increased over the past 20 years. Currently, autologous stem cell transplantation (ASCT) is the standard of care after primary therapy for eligible patients. Research has suggested a greater survival benefit after ASCT for patients < 60 years, but the role of ASCT in older individuals remains less clear. In order to better understand the impact of age on the outcome of myeloma patients receiving ASCT, we analyzed the presenting features and outcomes of 256 consecutive patients at our institution that received a first ASCT between January 2004 and December 2013. Patient characteristics were: median age 61 (range 32-76), Sex: M=55% F=45%, Immunochemical subtype: IgG=59%, IgA =21%, Light chain=16%, Other=4%, Durie-Salmon System (DSS) stage at diagnosis: Stage I=9%, Stage II=20%, Stage III=68%, Unknown=4%, Disease status at transplant: CR/sCRsp=18%, VgPR=27%, PR=49%, Stable=6%, Melphalan preparative dose: 200mg/m2=93%, 140mg/m2=7%. Second ASCT was eventually performed in 60 (23%) of patients, with 39 (15%) of these being planned tandem ASCT. Patient survival and disease status were collected prospectively as part of our comprehensive database. For purposes of analysis, patients were divided by age into three groups: age<55 (n=80), age 55-64 (n=90), age ≥ 65 (n=86). Groups were similar in regards to disease subtype, stage, status at the time of transplant, comorbidity index, and year of transplant; differences included more second transplants and tandem transplants in the youngest age group and more reduced dose melphalan in the oldest age group. At day +100 post-transplant, disease response was CR, VGPR, PR, and <PR in 35%, 24%, 39%, and 2%, respectively and did not differ statistically by age group. Non-relapse mortality at one-year post-transplant was 1%, and did not differ among the <55, 55-64, and ≥ 65 age-groups (0%, 3%, and 0%, respectively). With a median follow-up of 39 months, the estimated 4-year OS, DFS, and relapse incidence (RI) was 73%, 43%, and 48%, respectively. Survival and RI were significantly better in the younger age group (4-yr OS 84%, 70%, 64%; DFS 58%, 35%, 39%; RI 34%, 53%, 53%, respectively in the <55, 55-64, and ≥ 65 age-groups; see figure). Outcomes were extremely favorable in patients <55 years of age transplanted in CR or VGPR with a 4-yr OS, DFS, and RI of 96%, 75%, and 21%, respectively. Even in the older age groups, median overall survival had not been reached by 5 years, suggesting that all age groups benefit from ASCT. There were no statistically significant differences in measured outcomes between patients age 55-64 years and those age ≥ 65 years, confirming that age ≥ 65 years should not be used to determine transplant eligibility. In multivariate analysis, variables predictive of OS included age, disease stage, and year of transplant; whereas for DFS, predictive variables also included disease status at transplant and planned tandem ASCT (see table). This analysis builds on a growing body of evidence suggesting improved outcomes in patients with multiple myeloma. Patients regardless of age appear to benefit from ASCT, with median survival now exceeding 5 years in all age groups. Patients less than 55 years of age and particularly those achieving at least a VGPR prior to ASCT seem to represent a patient population with an extremely favorable prognosis post-transplant. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pre-Transplant M Protein Level Predicts Minimal Residual Disease Status after Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4903-4903
Author(s):  
Zachary S Meyer ◽  
Mohamed Manaa ◽  
Yan Han ◽  
Magdalena Czader ◽  
Attaya Suvannasankha ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Residual Disease ◽  
M Protein ◽  
Post Transplant ◽  
Minimal Residual

Abstract Introduction: Autologous stem cell transplantation has been a staple treatment modality in patients with multiple myeloma for more than 30 years. Multiple studies have shown increased survival among patients who undergo transplant when compared to those who receive chemotherapy alone, even amongst elderly patients. Despite the efficacy associated with transplant among populations as a whole, individual response to therapy is variable and difficult to predict. Recent studies however have demonstrated that achieving minimal residual disease (MRD) negativity is associated with increased survival in patients with multiple myeloma. In this study, we performed a retrospective analysis on patients with multiple myeloma who underwent autologous stem cell transplantation and investigated potential markers to predict post-transplant MRD status. Patients and Methods: Patients with a diagnosis of multiple myeloma that underwent treatment with high-dose melphalan followed by autologous stem cell transplantation at the Indiana University Simon Cancer Center between 2019-2020 were included in the analysis. Patient demographics, disease characteristics, pre-transplant and post-transplant laboratory values, and approximately day +100 post-transplant bone marrow sample results were collected. MRD analysis on post-transplant bone marrow aspirations was performed using 8 color flow cytometry panel with a total of 10 markers. The limits of quantification and detection were calculated at 5X10 -6 and 2X10 -6, respectively. Post-transplant data was analyzed to determine MRD status. MRD negativity was defined as having no identifiable M protein via serum protein electrophoresis (SPEP) or immunofixation electrophoresis (IFE) and having negative MRD on post-transplant bone marrow biopsy testing. Patients with insufficient data to determine post-transplant MRD status were excluded from the analysis. Univariate logistic regression was performed to assess the association of pre-transplant variables with post-transplant MRD status. Multivariate logistic regression model was utilized to analyze markers with a p-value &lt;0.25 in univariate analysis. Results: 133 Patients were included in the analysis with average age at transplant being 60.84 years (range 32.18 years-78.13 years). 83/133 (62.41%) patients were male and 118/133 (88.72%) patients were white. 84/133 (63.16%) patients had achieved a VGPR or less according to the International Myeloma Working Group (IMWG) response criteria prior to transplant. Among all patients, age at transplant, gender, race, body mass index, glomerular filtration rate on day -1, serum albumin on day -1, kappa/lambda ratio on day -1, melphalan dose received, and multiple myeloma immunoglobulin subtype were not associated with response to therapy. Pre-transplant M protein positivity was associated with a higher likelihood of post-transplant MRD positive status with an odds ratio of 24.318 (p&lt;0.0001). VGPR status or less on day -1 was associated with an increased post-transplant MRD positive status with an odds ratio of 6.223 (p&lt;0.0001) however was not found to be statistically significant following multivariate analysis (p=0.0664). When restricting analysis to include only patients at VGPR status or less prior to transplant, pre-transplant M protein positivity and increased age at transplant were associated with increased likelihood of MRD positive status with odd ratios of 9.000 (p=0.0121) and 1.066 (p=0.0366) respectively. Both variables were shown to be statistically significant following multivariate analysis. Conclusions: Detectable levels of pre-transplant M protein via serum protein electrophoresis is associated with an increased likelihood of having positive minimal residual disease following autologous stem cell transplantation in multiple myeloma. Age at transplant does not predict minimal residual disease status among all patients undergoing transplant, however increased age at transplant may be associated with inferior outcomes in patients achieving a VGPR or less prior to transplantation. Figure 1 Figure 1. Disclosures Suvannasankha: The Veteran's Affair: Patents & Royalties; Karyopharm: Consultancy, Research Funding; Regeneron: Research Funding; Sutro: Research Funding; Glaxo Smith Kline: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Abonour: Celgene-BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jensen: Honoraria, Research Funding; Takeda: Research Funding; GSK: Consultancy, Honoraria, Research Funding. Abu Zaid: Syndax: Consultancy, Research Funding; Pieris: Current equity holder in publicly-traded company; Incyte: Research Funding; Pharamcyclic: Research Funding.

Vaccination with Dendritic Cell Myeloma Fusions Alone or in Conjunction with Stem Cell Transplantation for Patients with Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3080-3080
Author(s):  
David Avigan ◽  
Jacalyn Rosenblatt ◽  
Baldev Vasir ◽  
Zekui Wu ◽  
Adam Bissonnette ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Immune Responses ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Tumor ◽  
Myeloma Cells ◽  
Post Transplant ◽  
Gm Csf ◽  
The Mean

Abstract Multiple myeloma expresses unique antigens that potentially serve as targets for tumor specific immunotherapy. Dendritic cells (DCs) are the most potent antigen presenting cells that prominently express costimulatory molecules and are uniquely able to stimulate anti-tumor immune responses. We have developed a promising cancer vaccine in which patient derived myeloma cells are fused with autologous DC resulting in the presentation of a broad array of tumor antigens in the context of DC mediated costimulation. DC/myeloma fusions potently stimulate anti-tumor immune responses in vitro as manifested by the lysis of autologous tumor targets. We are currently conducting phase I clinical trials in which patients with myeloma undergo serial vaccination with DC/myeloma fusions alone or in conjunction with stem cell transplantation. GM-CSF (100 μg) was administered subcutaneously on the day of vaccination and for 3 days thereafter. To date, 18 patients have been enrolled (11- vaccine alone, 7 vaccine transplant). To generate mature DCs, adherent mononuclear cells were isolated from a leukapharesis collection, cultured for 5 days with GM-CSF and IL-4 and terminal maturation was induced by exposure to TNFa for 48–72 hours. DCs prominently expressed HLA class II, costimulatory and maturation markers. The mean yield and viability of the DC preparations was 1.5 x 108 cells and 88%, respectively. Patient derived myeloma cells were isolated from bone marrow aspirates and were quantified by the expression of CD38 and/or CD138. The mean yield and viability of the myeloma cell collections was 7.3 x 107 cells and 89%, respectively. Fusion cells were generated by coculture of DCs with myeloma cells at a 3:1–10:1 ratio in the presence of 50% polyethylene glycol. Fusion cells were quantified by determining the percentage of cells that co-expressed unique DC and myeloma antigens. Mean fusion efficiency and viability of the fusion cell preparation was 40% and 84%, respectively. As a measure of immunologic potency, fusion cells prominently stimulated allogeneic T cell proliferation. To date, 13 patients have completed vaccination at a dose of 1–5 x 106 fusion cells. Adverse events judged to be potentially vaccine related have included vaccine injection site reactions, edema, rash, fever (infection), chills, fatigue, muscle aches, pruritis, and diarrhea. One patient with a history of prior deep venous thrombosis (DVT) developed a DVT and pulmonary embolus of uncertain relation to the vaccine. To date, 4/6 evaluable patients have demonstrated evidence of vaccine induced anti-myeloma immunity as demonstrated by at least 2 fold increase in IFNγ expression by CD4 and/or CD8 T cells in response to ex vivo exposure to autologous tumor lysate. Of patients undergoing vaccine therapy alone, 5 patients demonstrated stabilization of the myeloma paraprotein for 2–6 months following initiation of vaccination. Of 3 patients completing post-transplant vaccination, 1 patient demonstrated resolution of the persisting myeloma protein post-transplant, 1 patient exhibited stable post-transplant paraprotein levels for 6 months, and 1 patient demonstrated a transient increase followed by a progressive decline in paraprotein levels post-transplant.

Vaccination with DC/Multiple Myeloma Fusions in Conjunction with Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 578-578
Author(s):  
David Avigan ◽  
Jacalyn Rosenblatt ◽  
Baldev Vasir ◽  
Zekui Wu ◽  
Adam Bissonnette ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Regulatory T Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Tumor Immunity ◽  
Myeloma Cells ◽  
Post Transplant

Abstract Autologous transplantation results in the transient reversal of tumor mediated tolerance due to the reduction in disease bulk, the depletion of regulatory T cells, and in the increased presence of tumor reactive lymphocytes during the period of lymphopoietic reconstitution. As a result, cancer vaccines are being explored as a means of targeting residual myeloma cells following stem cell transplant. We have developed a cancer vaccine in which patient derived tumor cells are fused with autologous dendritic cells (DCs). In this way multiple tumor antigens are presented in the context of DC mediated costimulation. We are conducting a study in which patients with multiple myeloma (MM) undergo stem cell transplantation followed by vaccination with 3 doses of DC/MM fusions. DCs were generated from adherent mononuclear cells cultured with GM-CSF and IL-4 for 5–7 days and matured with TNFa. DCs strongly expressed costimulatory and maturation markers. Myeloma cells were isolated from bone marrow aspirates and were identified by their expression of CD38, CD138, and/or MUC1. DC and MM cells were fused with polyethylene glycol as previously described and fusion cells were quantified by determining the percentage of cells that coexpress unique DC and myeloma antigens. To date, 19 patients have been enrolled and 18 have completed vaccine generation. Mean yield of the DC and myeloma preparations was 1.84 × 108 and 8.3 × 107 cells, respectively. Mean fusion efficiency was 40% and the mean cell dose was 4.3 × 106 fusion cells. As a measure of their potency as antigen presenting cells, fusion cells prominently stimulated allogeneic T cell proliferation in vitro. Mean stimulation indexes were 12, 57, and 31 for T cells stimulated by myeloma cells, DCs, and fusion cells, respectively. Adverse events judged to be potentially vaccine related included injection site reactions, pruritis, myalgias, fever, chills, and tachycardia. Six patients have completed the follow up period and 3 patients are currently undergoing vaccination. All patients achieved a partial response to transplant. Three patients demonstrated resolution of post-transplant paraprotein levels following vaccination. One patient with highly aggressive disease who experienced disease progression in the early post-transplant period, demonstrated initial response and then stabilization of disease with vaccination. We are examining the effect of transplant and vaccination on measures of cellular immunity, anti-tumor immunity and levels or activated as compared to regulatory T cells. T cell response to PHA mitogen was transiently depressed post-transplant. In contrast, a transient increase was noted post-transplant in mean T cell expression of IFNγ in response to autologous myeloma cell lysate. In preliminary studies, a relative increase in the ratio of activated (CD4/CD25low) to regulatory (CD4/CD25high) T cells was observed. To date, all evaluable patients demonstrated evidence of vaccine stimulated anti-tumor immunity as manifested by a rise in IFNγ expression by CD4 and/or CD8+ T cells following ex vivo exposure to autologous tumor lysate. In this ongoing study, fusion cell vaccination in conjunction with stem cell transplantation has been well tolerated, induced anti-tumor immunity and clinical responses in patients with multiple myeloma.

Does Bisphosphonate-Induced Osteonecrosis of the Jaw (BONJ) Preclude Intensive Chemotherapy? Oral and Infectious Toxicities Associated with Autotransplantation In Patients with BONJ.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1314-1314
Author(s):  
Prakash Varadarajan ◽  
Juan Toro ◽  
Robert M. Craig ◽  
Deanna Schneider ◽  
Ju-Hsien Chao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conservative Management ◽  
The United States ◽  
Osteonecrosis Of The Jaw ◽  
Intensive Chemotherapy ◽  
Similar Frequency ◽  
Grade 3

Abstract Abstract 1314 Background: Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is a recently recognized adverse reaction associated with intravenous bisphosphonate use. The incidence of BONJ is estimated to be between 5–15% of patients with multiple myeloma (MM) treated with biphosphonates. Relevant to this complication, areas of osteonecrosis can harbor bacteria with the potential to cause infection and bacteremia during prolonged periods of myelosuppression. Furthermore, it is unclear if BONJ can worsen mucositis associated with cytotoxic therapy or if intensive chemotherapy can impair the healing of osteonecrosis. Since autologous peripheral blood stem cell transplantation (APBSCT) is an integral part of the treatment of MM, it is important to determine toxicities associated with APBSCT in patients with BONJ. Study Purpose: To determine the oral and infectious toxicities associated with APBSCT in patients with multiple myeloma and BONJ. Method: This is a retrospective analysis of patients with MM and BONJ who underwent APBSCT between January 2005 and June 2010. All the patients were evaluated for dental clearance by local dentists prior to referral to our institution. Before transplantation, all the patients underwent another oral evaluation by our institution's dentist who specializes in oral and maxillofacial pathology and is experienced in the evaluation and care of transplant patients. Results: During the study period, 176 patients underwent APBSCT for MM at our institution. Ten male patients, or 6% of all patients, were diagnosed with BONJ prior to transplantation. The median age of patients with BONJ was 60 years (range, 39–70). BONJ developed a median of 444 days (range, 187–2194) after the initiation of treatment with bisphosphonates. Patients with BONJ received a median of 15 infusions of biphosphonates (range, 6–60) before the diagnosis of BONJ was established. Six patients received zoledronate, 3 received pamidronate and one received both. Eight of the 10 patients with BONJ were diagnosed by our dentist. Five patients received dental care by local dentists a median of 5 months (range 1–7) before they were seen at our facility where they were examined by our dentist. Two of the five patients had received extractions placing them at risk of developing BONJ. None of the patients received radiation to the jaw or had lytic lesions in the jaw area. The transplant conditioning regimen was similar for all patients: melphalan 100 mg/m2 daily for 2 days. Six patients developed neutropenic fever for a median of 4 days (range, 1–9). Bacteremia was diagnosed in 3 patients and 1 met criteria for catheter-related bacteremia (CRB) as defined by the Centers for Disease Control of the United States. The incidence of CRB in patients with BONJ appears similar to the 13% CRB observed at our institution during the study period. The organisms isolated from the blood were Pseudomonas aeruginosa, Corynebacterium species, Sphingomonas paucimobilis and Coagulase-negative staphylococcus, the last 2 were cultured from one patient. None of these organisms are predominantly found in the oral cavity but have been well described as pathogens in immunosuppressed hosts. Seven patients with BONJ developed mucositis posttransplantation but only one patient experienced grade 3 mucositis as defined by the Common Toxicity Criteria version 3. Of the remaining patients, 3 developed grade 1 and 3 developed grade 2 mucositis posttransplantation. Patients without BONJ had a similar frequency of mucositis: 31% of patients did not experience any mucositis, another 31% developed grade 1, 30% developed grade 2 and only 7% developed grade 3 mucositis. There was no treatment-related mortality within one year posttransplantation. So far, only 1 patient has died of progressive disease 13 months after APBSCT. Of interest, BONJ healed in nine patients posttransplantation with conservative management and 3 patients had bisphosphonates reintroduced with no recurrence of BONJ. Conclusion: Autologous stem cell transplantation can be performed safely in patients with BONJ. The incidence of oral and infectious toxicities observed in patients with BONJ appears similar to the incidence observed in patients without BONJ transplanted during the same period of time. BONJ was not recognized by most practitioners who referred patients for transplantation. Finally, BONJ healed in most patients after the transplant with conservative management. Disclosures: No relevant conflicts of interest to declare.

Effect of Melphalan 140 Mg/m2 Versus 200 Mg/m2 on Toxicities and Outcomes in Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1988-1988
Author(s):  
Lakshmikanth Katragadda ◽  
Lindsay McCullough ◽  
Yunfeng Dai ◽  
Jack W Hsu ◽  
John W Hiemenz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Cox Proportional Hazards Model ◽  
Hematopoietic Stem ◽  
Preparative Regimen

Abstract Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m2 ( MEL-200). Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m2 or 200 mg/m2. Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes. Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P=<0.001) or had cardiac ejection fraction < 50 (P=0.0001) or had Karnofsky score < 80 (P=0.01) or had creatinine > 2 either at diagnosis (P=0.004) or the time of ASCT (P=0.001). Rest of the patient and disease characteristics including Durie-Salmon stage, myeloma subtype and disease status at ASCT were not significantly different between the 2 arms. Patients in MEL-140 needed significantly longer time to ANC engraftment (P=0.037) and also had significantly higher frequency of neutropenic fever (P=0.003). There were no significant differences in mucositis (including grade), nausea, vomiting, diarrhea, bacteremia, or length of hospital stay and frequency of repeat hospitalizations among both groups. There was no treatment related mortality in either group. At a median follow up of 74 months (range, 52-140) from ASCT, there were no significant differences in relapse free survival (RFS) (P=0.4988) and overall survival (OS) (P=0.6936) between the two groups. Five year OS for MEL-140 and MEL-200 is 71.6% and 78.9%, while RFS is 23.9% and 34%, respectively. Proportion of patients whose myeloma status improved to ≥ VGPR at 3 months post ASCT was also not different (P=0.385). Importantly, similar proportions of patients received various post ASCT maintenance therapy (P=0.605). In multivariate cox proportional hazards model only disease status of ≥VGPR at the time of ASCT significantly affected RFS (P=0.024) but did not impact OS (P=0.104). Conclusion: MM patients who received MEL-140 had similar long term outcomes as those who received MEL-200 despite their older age, lower performance status and renal insufficiency. Disclosures No relevant conflicts of interest to declare.

Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4356-4356 ◽  
Author(s):  
Veronica Gonzalez De La Calle ◽  
Eduardo Sobejano ◽  
Julio Davila ◽  
Enrique M Ocio ◽  
Noemi Puig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
B Lymphocyte ◽  
Disease Stage ◽  
Advisory Committees

Abstract BACKGROUND High dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old). Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT. AIMS The goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM). METHODS We reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression. RESULTS 106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%). Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03). Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007). CONCLUSIONS The lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. Disclosures Ocio: Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study

2020 ◽  
Vol 8 (1) ◽  
pp. e000286 ◽  
Author(s):  
Benjamin A Derman ◽  
Yuanyuan Zha ◽  
Todd M Zimmerman ◽  
Rebecca Malloy ◽  
Andrzej Jakubowiak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Ex Vivo ◽  
Conditioning Regimen ◽  
High Dose ◽  
Treg Depletion ◽  
Post Transplant

BackgroundProgression after high-dose melphalan with autologous stem cell transplantation (ASCT) in multiple myeloma (MM) may be due in part to immune dysfunction. Regulatory T (Treg) cells reconstitute rapidly after ASCT and inhibit immune responses against myeloma cells.MethodsWe performed a randomized study to evaluate two methods of Treg depletion in patients with MM undergoing ASCT. No Treg depletion was performed in the control ASCT arm. An anti-CD25 monoclonal antibody (basiliximab 20 mg IV) was administered on day +1 post-ASCT in the in vivo Treg depletion (IVTRD) arm. Tregs were depleted from autologous stem cell (ASC) grafts with anti-CD25 microbeads and the CliniMACS device in the ex vivo Treg depletion (EVTRD) arm.ResultsFifteen patients were enrolled, five in each arm. The conditioning regimen was melphalan 200 mg/m2. Primary objectives included assessments of efficiency of IVTRD/EVTRD, kinetics of Treg depletion and recovery following ASCT, and safety. EVTRD removed 90% of CD4+CD25+cells from ASC grafts. IVTRD and EVTRD led to reductions in Treg frequency between days +7 and +90 post-transplant compared with the control (p=0.007 and p<0.001, respectively).ConclusionsIVTRD and EVTRD are feasible and significantly reduce and delay Treg recovery post-ASCT for MM, and serve as a platform for using post-transplant immunotherapies to improve post-ASCT outcomes.Trial registration numberNCT01526096.

scholarly journals Autologous Stem Cell Transplantation in Multiple Myeloma Patients Over 60 Years Old

2021 ◽  
Author(s):  
Bahar Uncu Ulu ◽  
Tuğçe Nur Yiğenoğlu ◽  
Semih Başcı ◽  
Mehmet Bakırtaş ◽  
Derya Şahin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Treatment ◽  
High Dose ◽  
Age Group ◽  
Study Results

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and p<0.00, respectively). Our study indicated that a high dose (200 mg/m2 ) melphalan could safely be used in the physically fit patients at the ages of 60-69, and a reduced amount (140 mg/m2 ) would be the appropriate dose for the patients over 70. The quantity of infused CD34+ stem cells affect elderly MM patients; mobilization dynamics are also important factors for elderly myeloma. Age itself should not consider a barrier to ASCT, and a comprehensive geriatric evaluation should perform on elderly patients

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