scholarly journals Autologous Stem Cell Transplantation for Multiple Myeloma Patients Aged ≥ 75 Treated with Novel Agents

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Iuliana Vaxman ◽  
Alissa Visram ◽  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Mayo Clinic ◽  
Research Funding ◽  
Advisory Board ◽  
Novel Agents

Introduction Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65 years of age. The definition of transplant eligible is ill-defined and different centers have different policies to determine which patients are transplant eligible. Some centers have an age cut-off, others use clinical judgment, and some use various frailty scores (a scoring system based on comorbidities and physical and cognitive assessments) aiming to objectively assess transplant eligibility. There are limited data about outcomes in patients ≥ 75 years. Aim To report on outcomes of ASCT in a cohort of patients with MM aged 75 years or older. Methods Retrospective study of all consecutive MM patients aged ≥ 75 years that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Stem cell transplantation at our center is routinely performed as an outpatient, with patients being hospitalized when deemed clinically necessary upon physician review. Results Between October 2005 and March 2020, 46 patients aged 75 years or older, received an ASCT at Mayo Clinic, Rochester. The median hematopoietic stem cell transplantation specific comorbidity index (HCT-CI) was 0 (range 0-6) with 8 patients having HCT-CI of 5 or 6. Median time from diagnosis to ASCT was 6.45 months (IQR 5.2-10.52) and 54% received reduced intensity conditioning with melphalan 140 mg/m2. All patients except one (that was treated with dexamethasone only) received induction with novel agents (listed in table 1) and 6 patients (13%) received doublet induction. All others received triplet induction. 46% of patients completed the ASCT without requiring hospitalization and 54% (n=25) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%) and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients and 16 patients achieving MRD negative sCR. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. Univariable cox regression model that evaluated the effect of gender, high risk cytogenetics, hemoglobin, renal function and melphalan dose did not detect any variable that was predictive of OS or PFS (Table 3). Conclusions ASCT is efficacious and can be safely delivered in the outpatient setting in carefully screened patients aged 75 or above. An arbitrary cutoff for age should not be used to exclude patients from ASCT, rather a careful assessment of "physiological age" including performance status and co-morbidities is required by an experienced treating team. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Cellectar: Other; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; MedImmune: Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Adaptive Biotechnologies: Consultancy. Dispenzieri:Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Dingli:Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy. Kapoor:Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Gertz:Prothena: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Janssen: Other: personal fee; Research to Practice: Other; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Other; Springer Publishing: Patents & Royalties; Celgene: Other; Physicians Education Resource: Other: personal fee; Aurora Bio: Other; Amgen: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Abbvie: Other.

Up-Front Therapy for Multiple Myeloma: A Survey of Practice Patterns in the USA.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5172-5172
Author(s):  
Kavita Natarajan ◽  
Gary H. Lyman ◽  
Oscar F. Ballester
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Initial Therapy ◽  
Newly Diagnosed ◽  
The Usa ◽  
Choice Of Therapy

Abstract Introduction: Several treatment programs are available for the initial management of patients with multiple myeloma, with no clear documented advantage(s) of one regimen over the others in terms of time to progression (TTP) or overall survival (OS). Materials and Methods: A questionnaire was mailed to 540 randomly selected members of ASH during early 2005. Practitioners were asked their choice of therapy for newly diagnosed myeloma patients during 2004, based on 2005 NCCN guidelines, including: 1) melphalan/prednisone (MP), 2) vincristine / adriamycin / decadron (VAD), 3) high-dose decadron (HD), 4) thalidomide / decadron (Thal/Dex), 5) doxyl / vincristine / decadron (DVD); the options of a clinical trial (CT) or “other” were also included. Physicians were asked about factors influencing their choice of therapy for individual patients and their recommendations for autologous stem cell transplantation as part of the initial treatment schema. Results: Surveys were returned by 123 physicians(19.2%), of which 93 contained evaluable data. Among responders, 52% were in private practice and 47% in academic institutions and 74% respondants reporting having been in practice for more than 10 years. A large majority of physicians (74%) utilized 3 or more different regimens, only 10.7% of responders used a single regimen for all of their patients. Thal/Dex was used by 87% of responders, with 47% of them recommending this regimen in ≥ 50% of their patients. MP, HD and VAD were used by 67.7%, 49% and 44% of responders, but only 10.7%, 4% and 3% respectively, recommended them to ≥ 50% of their patients. DVD was used by 25% of physicians. Of respondants, 64.5% did not accrued patients to clinical trials and only 7.5% of physicians accrued ≥ 50% of their patients to clinical trials. No significant differences in the choice of regimen were apparent based on years of practice. Physicians in academic centers tended to use HD (p =.002) and accrue patients to CT (p=. 001) more often than those in private practice. Factors identified as important in selecting initial therapy for individual patients included: age (92%); performance status (95%); prognostic factors, such as β2-microglobulin and cytogenetics (75%); and candidacy for stem cell transplantation (93%). Respondants consider autologous stem cell transplantation as part of the initial therapy for all eligible patients (47%), only those with responsive disease (42%) and normal renal function (30%); only in selected cases (76%). Conclusions: Thal/Dex appears to be currently the most commonly recommended up-front therapy for multiple myeloma in the USA, in spite of the lack of published data documenting patient benefit in terms of TTP and OS. A sizable proportion of physicians do not recommend autologous stem cell transplantation as part of the initial therapy of newly diagnosed myeloma patients despite confirmed randomized clinical trials documenting benefit.

Secondary Primary Malignancies in Patients with Multiple Myeloma Treated with High-Dose Chemotherapy and Autologous Blood Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4087-4087 ◽  
Author(s):  
Roland Fenk ◽  
Florian Neubauer ◽  
Ingmar Bruns ◽  
Christian Saure ◽  
Thomas Schroeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Blood Stem Cell ◽  
Novel Agents ◽  
High Dose ◽  
Blood Stem Cell Transplantation

Abstract Abstract 4087 Introduction: Secondary primary malignancies (SPM) are an emerging issue in patients with multiple myeloma (MM) since the French IFM 99–02 trial has been closed as a consequence of a higher incidence of SPM in patients who had received lenalidomide as maintenance treatment compared to the patients in the placebo arm. Methods: To evaluate the incidence of SPM in the group of patients, who were treated with high-dose therapy (HDT) followed by autologous peripheral blood stem cell transplantation (PBSCT), we retrospectively looked at a homogeneous group of 313 consecutive patients, who were diagnosed with MM and had received HDT and autologous PBSCT at our hospital between December 1994 and January 2009. Induction treatment consisted of conventional chemotherapy without novel agents in 95% of patients and maintenance treatment was given with interferon or thalidomide in 37% und 35% of patients, respectively. Results: Within 313 patients with a median age of 55 (range: 31–74) years at diagnosis, we observed 18 (5.8%) patients who developed a SPM at various time points during the course of their disease. The number of patients who developed a solid neoplasm or a hematologic malignancy was identical. While the types of solid tumor observed varied greatly, we noted 8 patients with MDS/AML and only one patient with Hodgkins Disease. The median time from diagnosis of MM to the occurrence of SPM was 56 months (range: 14–127). The cumulative incidence of SPM was 19.7% with a rate of 0.7%, 5.8% and 15.7% at 2, 5 and 10 years after diagnosis without statistical differences between the group of patients with solid tumors (0.3%, 4.4%, 7.5%) and those with hematologic malignancies (0.4%, 1.8%, 9.3%). OS from the time of diagnosis in our group of 18 patients with SPM was not significantly different from that of patients without SPM with in median 70 and 83 months (p=0.7, HR 0.9 (0.5–1.7)), respectively. The same was true, when a landmark analysis was performed for patients alive after 2, 5 and 8 years with hazard ratios of 0.9 (95%CI 0.5–1.7, p=0.8), 0.6 (95%CI 0.3–1.4, p=0.2) and 1.0 (95%CI 0.2–4.3, p=1.0), respectively. In line with this finding, we found that survival time of more than 5 years from the time of diagnosis was the only prognostic parameter indicating a greater risk for the development of SPM (HR 4.7 (95%CI 1.1–19.8), p=0.04). In particular, we did not find any relationship to the incidence of SPM and the treatment with novel agents. The incidence rate of 206 patients, who were exposed to thalidomide was 6% (n=13, HR1.4 (95%CI 0.5–4.0), p=0.5), while of the 123 patients exposed to bortezomib 5 developed a SPM (4%, HR 0.4 (95%CI 0.1–1.1), p=0.1). There were two cases of SPM among the 71 patients following lenalidomide treatment (3%, HR 0.4 (95%CI 0.1–1.5), p=0.2). Having a closer look at the maintenance setting, which is associated with a longer duration of drug exposure, we did not find a higher incidence of SPM in patients treated with thalidomide maintenance after HDT in comparison to patients who had received interferon or no maintenance therapy (HR 1.0, 95%CI 0.3 – 3.2, p=1.0). Conclusions: In conclusion, the incidence of SPM in patients with MM treated with HDT is increased, especially for patients with a prolonged life span. SPM were not related to various treatment modalities including maintenance treatment with thalidomide. As a consequence on the available data, physicians should be aware of the risk of SPM and diagnostic measures to detect SPM should be included in the daily clinical workup of patients with MM. Disclosures: Fenk: Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy. Germing:Celgene: Consultancy, Research Funding. Gattermann:Celgene: Consultancy, Research Funding. Kobbe:Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy.

scholarly journals Impact of Daratumumab-Containing Induction on Stem Cell Mobilization and Collection, Engraftment and Hospitalization Parameters Among Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3886-3886
Author(s):  
Evangelos Eleutherakis Papaiakovou ◽  
Evangelos Terpos ◽  
Nikolaos Kanellias ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Treated Group ◽  
High Dose ◽  
On Demand ◽  
Increased Risk

Abstract Introduction: Advances in induction regimens have significantly improved depth of response and duration of remission in multiple myeloma (MM) patients who are eligible for high-dose therapy and autologous stem cell transplantation (ASCT). Proteasome inhibitor-based induction regimens are standard as part of induction and it has been shown not to have any detrimental effect on stem cell (SC) collection and engraftment. Daratumumab (DARA) is an IgG1k monoclonal antibody directed against CD38 with potent antimyeloma activity. Based on the results of prospective studies DARA is now approved as part of induction therapy. Available data indicate a potential impact of DARA on SC collection but there is limited data on engraftment, duration of hospitalization and infection risk. In this retrospective analysis we evaluated the effect of DARA-based induction on ASCT parameters. Methods: The analysis included consecutive newly diagnosed MM patients that received ASCT between 2016 and 2020, as part of their upfront treatment regimen in our institution (Department of Clinical Therapeutics, Athens, Greece). Per institutional protocol, after 4-6 cycles of induction, pts received low dose cyclophosphamide (2.5 g/m2) followed by G-CSF (10 mcg/Kg/day) to mobilize and collect SCs. Plerixafor was administered on-demand in case of poor mobilization and insufficient first day collection. Large volume leukapheresis was performed in pts with low CD34+ counts in order to increase CD34+ yield. Pts received G-CSF 480 μcg once daily from day +4 after SC reinfusion to ANC >1500/mm3. All pts received antiviral and antifungal but no anti-bacterial prophylaxis. Results: 200 eligible pts were included in the analysis; 40 (20%) pts received DARA as part of PI-based upfront treatment and 160 (80%) pts received PI-based upfront treatment without DARA. Baseline demographics (age, gender, performance status) and disease characteristics (ISS and R-ISS stage, cytopenias, eGFR, lytic bone disease etc) were not different between the two groups. Response after induction was also similar (CR+VGPR rate was 93% vs 95% for non-DARA and DARA-containing regimens respectively). Use of DARA at induction was associated with lower total mean number of collected CD 34+ SCs (10.48 x 10^6/kg vs 16.58 x 10^6/kg, p<0.0001), or SC collection on day 1 (7.99 x 10^6/kg vs 16.27 x 10^6/kg, p<0.0001). Fewer pts in the DARA-treated group achieved the planned yield of at least 5 X 10^6 CD34+/kg, compared to DARA-untreated group (87.5 % vs 96.2%, p=0.047). DARA-treated pts required more often additional SC mobilization with on demand administration of plerixafor (42.5% vs 7.6%, p<0.0001). In order to compensate for a poorer mobilization and lower quality graft (CD34% 0.66% vs 1.26% in apheresis product, p<0.0001) DARA-treated group underwent more often >1 day of SC collection (37.5% vs 6.3%, P <0.0001), resulting in longer duration of collections (689 vs 452 min, p<0.0001) and larger total apheresis volumes (723 vs 557 ml, p<0.0001). However, 97% and 98% of pts in the two groups respectively were able to move to at least a single ASCT. Following ASCT, DARA-treated pts had a slightly delayed hematopoietic recovery (11 vs 10 days to PMN>500/mm3, p<0.001 and 12 vs 11 days for PLT counts> 25x10^9/mm3, p<0.001) and required more transfusions (2 vs 1 for RBCs, p=0.031 and 4 vs 2 for platelets, p<0.001). Rates of neutropenic fever were higher (80% vs 67%, p=0.182), required antibiotics for longer duration (10 vs 8 days, p=0.042) and more often 2 or more lines of antibiotic therapy (53% vs 39%, p=0.003), experienced more often septic shock (12.5% vs 1.3%, p=0.003) and as a results DARA-treated pts had a slightly prolonged hospitalization (21 vs 19 days, p=0.02). However, D100 mortality was not statistically different (<2% in both groups). Conclusion: DARA-containing induction before ASCT is associated with poorer mobilization and frequent need for use of plerixafor. However, similar percentage of patients can move to at least a single ASCT. The use of DARA-containing induction was also associated with slightly increased risk of infectious complications, antibiotics use and blood product transfusions but no increase in the risk of D100 mortality. These data point to the need for certain modifications to ASCT protocol for patients treated with DARA-containing regimens at induction, such as preemptive use of plerixafor, and perhaps prophylactic antibiotics. Disclosures Terpos: Amgen: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding. Gavriatopoulou: Takeda: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Dimopoulos: Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; BeiGene: Honoraria. Kastritis: Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Janssen: Consultancy, Honoraria, Research Funding.

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 <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<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<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.

scholarly journals Decreased Cardiac Ejection Fraction Is Associated with Worse Survival in Patients with Light Chain Amyloidosis Treated with Autologous Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Abdullah S. Al Saleh ◽  
Iuliana Vaxman ◽  
Harsh Parmar ◽  
Alissa Visram ◽  
M Hasib Sidiqi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ejection Fraction ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Light Chain ◽  
Research Funding ◽  
Cardiac Involvement ◽  
Advisory Board ◽  
Al Amyloidosis

Introduction: Cardiac involvement is one of the main predictors for survival in patients with light chain (AL) amyloidosis. Biomarkers such as Troponin T and N-terminal pro b-type natriuretic peptide (NT-proBNP) are used routinely for detecting cardiac involvement. In addition echocardiogram (ECHO) is used to determine septal and left ventricular wall thickness and strain. Most patients with AL present with preserved ejection fraction (EF) however, the outcomes of AL patients undergoing autologous stem cell transplantation (ASCT) with decreased EF are not very well described. Methods: We retrospectively reviewed patients who had a diagnosis of AL amyloidosis and received ASCT between March 1996 and September 2017. All patients had an ECHO done before ASCT and the EF was documented. In our practice, the threshold for performing ASCT is an EF >40%. We evaluated the outcomes of patients who had an EF <55% compared to patients with an EF ≥55%. The baseline characteristics were compared between patients with high and low EF. Progression-free survival (PFS) was defined as time from ASCT to disease progression, relapse, or death of any cause. Overall survival (OS) was calculated from time of ASCT to death of any cause. Univariate and multivariate analysis for PFS and OS were done using the following variables: age>65 vs. ≤65 years, Mayo 2012 stage 3/4 vs. 1/2, bone marrow plasma cell percentage (BMPC) ≥ 10% vs. <10%, organs involved >2 vs. ≤2, melphalan conditioning 200mg/m2 vs. 140 mg/m2 ,ASCT year >2010 vs. ≤2010, and EF <55% vs. ≥55%. Results: We identified 716 patients and 69 (10%) had an EF<55%, with most (n=63, 91%)having cardiac involvement . Compared to patients with EF ≥55%, patients with EF <55% were more likely to have Mayo 2012 stage 3/4 (58% vs. 22%, P<0.0001) and more likely to have thicker interventricular septum (median 14 vs. 12 mm, P<0.0001). The day 100 transplant related mortality (TRM) was higher in patients with EF <55% compared to EF ≥55% (19% vs. 6%, P=0.0006). In patients with Mayo 2012 stage 3/4, the day 100 TRM was higher in patients with an EF<55% compared to EF ≥55% (27% vs. 7%, P=0.004). Overall, PFS and OS were significantly shorter in patients with EF <55% compared to patients with EF ≥55% (Figure 1 A,B). Evaluating PFS and OS according to EF specifically in Mayo 2012 stage 3/4 patients is displayed in Figure 1 (C,D). Predictors for PFS included Mayo 2012 stage 3/4 vs. 1/2 (hazard ratio (HR): 1.4, P=0.006), BMPC ≥ 10% vs. <10% (HR: 1.5,P=0.0005), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.7, P=0.01), ASCT year >2010 vs. ≤2010 (HR: 0.7, P=0.01), and EF <55% vs. ≥55% (HR: 1.5, P=0.02). For OS, age >65 vs. ≤65 years (HR:1.4, P=0.04), Mayo 2012 stage 3/4 vs. 1/2 (HR: 1.96, P<0.0001), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.5, P<0.0001), BMPC ≥ 10% vs. <10% (HR: 1.8, P=0.03), ASCT year >2010 vs. ≤2010 (HR: 0.5, P<0.0001), and EF <55% vs. ≥55%(HR:1.9, P=0.003) were predictive. Conclusion: Having an EF <55% is associated with a higher day 100 TRM and is an independent predictor for PFS and OS in patients with AL amyloidosis undergoing ASCT. Disclosures Sidiqi: Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Other: Travel grant. Dingli:Alexion: Consultancy; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy; Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Janssen: Consultancy; Rigel: Consultancy. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Takeda: Honoraria, Research Funding; Amgen: Research Funding. Dispenzieri:Janssen: Research Funding; Pfizer: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Kumar:AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Merck: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Sanofi: Research Funding; MedImmune: Research Funding; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Genecentrix: Consultancy; Cellectar: Other; Carsgen: Other, Research Funding. Gertz:Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Sanofi: Other; Research to Practice: Other; Celgene: Other; Medscape: Other: personal fee, Speakers Bureau; Proclara: Other; DAVA oncology: Speakers Bureau; Alnylam: Other: personal fee; Johnson and Johnson: Speakers Bureau; Physicians Education Resource: Other: personal fee; Teva: Speakers Bureau; Ionis/Akcea: Other: personal fee; Amgen: Other: personal fee; Springer Publishing: Patents & Royalties; Aurora Bio: Other; Appellis: Other: personal fee; Abbvie: Other; Annexon: Other: personal fee; Prothena: Other: personal fee.

High Dose Therapy with Autologous Stem Cell Transplantation Vs Standard Dose Chemotherapy In Multiple Myeloma: A Meta-Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3559-3559
Author(s):  
Florian Faußner ◽  
Markus Pfirrmann ◽  
Wolfram Dempke
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Additional Data ◽  
Standard Dose ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 3559 Introduction. Myeloablative high dose chemotherapy (HDT) followed by single autologous stem cell transplantation is currently the standard treatment for patients younger than 65 years in newly diagnosed multiple myeloma (MM). Several randomized controlled trials (RCTs) comparing HDT with standard dose therapy (SDT) have shown some benefit in overall survival (OS) and progression free survival (PFS), whereas other RCTs did not confirm this finding. Koreth et al. (2007) performed a metaanalysis summarizing the existing data of the RCTs including 2,411 patients. These authors found a significant superiority for HDT in PFS but not in OS. Since a number of new studies have been published recently, we attempted to re-analyze the current data in terms of the endpoints OS and PFS. Methods. We searched PubMed, Embase, abstracts of former ASH meetings and ClinicalTrials.gov as well as bibliographies of included trials and recent reviews from september 2009 until may, 20th 2010. Amongst the 3,484 results in this search we identified 10 RCTs comparing HDT with SDT on an intent-to-treat-basis. Treatment characeristics and outcomes of OS and PFS were calculated using R. Furthermore, we tested for statistical heterogenity, publication bias and performed subgroup analyses. Results. 9 RCTs including 2,600 patients were fully analyzed. Patients undergoing HDT with stem cell transplantation did have significant PFS benefit (Hazard Ratio 0.73; 95% conficence intervall 0.56–0.95; P=0.02) but not OS benefit (HR 0.90; 95% CI 0.74–1.10; P=0.32) compared to patients undergoing SDT. Additional data from ongoing clinical trials are expected, thus updated results at the meeting including 10 RCTs with about 3,400 patients will be presented. Conclusion. Although there is only a trend to OS benefit with HDT, it is currently still the first line treatment. Additional data from ongoing clinical trials and new studies using novel agents like thalidomide, lenalidomide and bortezomib are egerly warrented to finally evaluate the role of HDT in the treatment management of patients with newly diagnosed MM. 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.

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