scholarly journals Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Agents: Impact of Depth of Response to Induction Therapy. A Single Institution Experience

2011 ◽  
Vol 17 (2) ◽  
pp. S203
Author(s):  
M.G. Tapia ◽  
K. Olarte ◽  
R. Mckinnon ◽  
K. Ruemenapp ◽  
N. Janakiraman
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Novel Agents ◽  
Single Institution ◽  
Depth Of Response

scholarly journals Circulating monocyte subsets in multiple myeloma patients receiving autologous stem cell transplantation – a study of the preconditioning status and the course until posttransplant reconstitution for a consecutive group of patients

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ida Marie Rundgren ◽  
Elisabeth Ersvær ◽  
Aymen Bushra Ahmed ◽  
Anita Ryningen ◽  
Øystein Bruserud
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Monocyte Subset ◽  
Immunomodulatory Drugs ◽  
Monocyte Subsets ◽  
Classical Monocytes

Abstract Background Induction therapy of multiple myeloma patients prior to autologous stem cell transplantation has changed from conventional chemotherapy to treatment based on proteasome inhibitors or immunomodulatory drugs. We used flow cytometry to analyze total monocyte and monocyte subset (classical, intermediate and non-classical monocytes) peripheral blood levels before and following auto-transplantation for a consecutive group of myeloma patients who had received the presently used induction therapy. Results The patients showed normal total monocyte concentrations after induction/stem cell mobilization, but the concentrations of classical monocytes were increased compared with healthy controls. Melphalan conditioning reduced the levels of total CD14+ as well as classical and non-classical monocytes, whereas intermediate monocytes were not affected. Thus, melphalan has a non-random effect on monocyte subsets. Melphalan had a stronger effect on total and classical monocyte concentrations for those patients who had received induction therapy including immunomodulatory drugs. Total monocytes and monocyte subset concentrations decreased during the period of pancytopenia, but monocyte reconstitution occurred before hematopoietic reconstitution. However, the fractions of various monocyte subsets varied considerably between patients. Conclusions The total level of circulating monocytes is normalized early after auto-transplantation for multiple myeloma, but pre- and post-transplant levels of various monocyte subsets show considerable variation between patients.

scholarly journals Autologous Stem Cell Transplantation in Elderly Patients with Multiple Myeloma: Past, Present, and Future

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Shuji Ozaki ◽  
Kazuyuki Shimizu
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Agent Based ◽  
Reduced Intensity ◽  
Novel Agent

High-dose melphalan (200 mg/m2) as conditioning regimen followed by autologous stem cell transplantation (ASCT) rescue has been established as a standard treatment for patients with multiple myeloma (MM) younger than 65 years of age. However, the role of ASCT in elderly patients older than 65 years remains controversial in the era of novel agents such as thalidomide, bortezomib, and lenalidomide. The efficacy and feasibility of ASCT have been shown in elderly patients by reducing the dose of melphalan to 100–140 mg/m2. Although the clinical benefit of reduced-intensity ASCT in elderly patients has not been clearly established in comparison with that of novel agent-based induction therapy, recent studies have demonstrated that sequential strategies of novel agent-based induction therapy and reduced-intensity ASCT followed by consolidation/maintenance with novel agents translate into better outcome in the management of elderly patients. Thus, ASCT could also be a mainstay in the initial treatment of elderly MM patients, and its indication should be evaluated based on performance status and the presence of complications and/or comorbidities of each elderly patient with MM.

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.

Depth of Response with Stem Cell Transplantation and Outcome for Multiple Myeloma in the Era of Novel Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1228-1228
Author(s):  
David Dingli ◽  
Francesca Gay ◽  
Francis Buadi ◽  
Angela Dispenzieri ◽  
Suzanne R Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Novel Agents ◽  
Cell Transplant ◽  
Time To Progression ◽  
Depth Of Response ◽  
The Impact

Abstract Abstract 1228 Poster Board I-250 Background It is generally believed that a ‘deeper’ response in multiple myeloma is associated with an improved outcome, including time to progression (TTP) as well as overall survival. Before the advent of novel agents such as IMiDs or bortezomib, complete responses (CR) were rare in the absence of stem cell transplantation (ASCT). In that era, the depth of response achieved before ASCT tended to be dwarfed by the impact of the conditioning used for stem cell transplant. Hence, the time to progression in patients achieving CR before ASCT was not different from those who achieved CR after ASCT. With novel agents, CR rates are higher and again raises the question of whether patients who achieve CR before ASCT benefit from consolidation with ASCT. The purpose of this analysis was to determine whether CR achieved before ASCT still benefit when consolidated with ASCT Methods After approval from the Institutional Review Board at Mayo Clinic Rochester, the transplant dysproteinemia database was searched for all patients treated with novel agents and patients who achieved CR before or after ASCT were identified. In addition, we identified patients with IMiDs induction therapy and achieved CR but did not proceed with ASCT. Relevant demographic, clinical and laboratory characteristics were determined at the time of ASCT. Comparisons between groups were performed with non-parametric tests. Overall survival and TTP were determined from the time of ASCT using the Kaplan-Meier method. Results A total of 354 patients who underwent ASCT within a year from diagnosis of multiple myeloma were identified. Of these, 24 achieved CR before proceeding to ASCT while another 100 patients achieved CR after ASCT. There were no differences between the two cohorts with respect to age (58 vs 57.5 yr, p=0.14), gender, number of treatment regimens (1 vs 1, p=0.83), time to ASCT (6.5 vs 6.3 months, p=0.80), b2M (2.41 vs 2.26, p=0.58) and ISS (p=0.23). Patients who achieved CR before ASCT had a lower plasma cell burden (1.0 vs 5.0%, p<0.0001) and lower labeling index (0 vs 0, p=0.0007). Aneuploidy was present in none of the patients with CR before transplant compared to 10% in patients who achieved CR after ASCT (p=0.11). The median TTP for patients with CR before ASCT has not been reached (71% at 70 months) compared to 30 months for patients who achieved CR after ASCT (p=0.07). After a median follow up of 70 months, 21 of 24 patients (88%) with CR before transplant are alive compared to 76 of 100 patients with CR after ASCT (p=0.44). In contrast, for patients who achieved CR with IMiDs but did not proceed with ASCT, 55% have not progressed at 51 months and 71.7% are alive at 51 months (Gay et al ASH, 2009). Conclusion Our results suggest that patients who achieve CR before ASCT benefit from high-dose therapy and experience prolonged TTP without the need for maintenance therapy. ASCT after achieving CR can result in a deeper response with improvement in disease free and overall survival. Disclosures Lacy: celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria.

Survival Impact of Response with Bortezomib Induction on Myeloma Patients Receiving Autologous Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4590-4590
Author(s):  
Chang-Ki Min ◽  
Hyeon Seok Eom ◽  
Byung Sik Cho ◽  
Yoo-Jin Kim ◽  
Hee-Je Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Objective Response ◽  
Novel Agents ◽  
Induction Treatment ◽  
Post Transplant

Abstract Abstract 4590 Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) aged less than 65 years. Before the era of novel agents the absence of initial response to induction therapy had no impact on outcome after ASCT. With the introduction of novel agents response rate with initial therapy are now between 70% and 100%. This study analyzes the association of progression-free survival (PFS) and overall survival (OS) after ASCT with the response to induction therapy with a regimen that contains bortezomib for patients with MM. We performed a retrospective analysis of 61 patients with MM who consecutively received bortezomib-containing regimens from 2 institutes before collection of peripheral blood stem cells and ASCT. The median age was 54 (34-65) years and 41 (67.2%) were male. Eight (16.4%) patients received bortezomib as a first-line therapy whereas the others as the second line or more. Melphalan alone was used for conditioning and 29 (47.5%) received thalidomide maintenance therapy. Fifty four of 61 patients (88.5%) achieved objective response after bortezomib induction treatment. Post-bortezomib complete response (CR), very good partial response (VGPR) and partial response (PR) were present in 33 (54.1%), 6 (9.8%) and 15 (24.6%), respectively. After ASCT CR, VGPR and PR were 41 (67.2%), 3 (4.9%) and 6 (9.8%), respectively. Achieving CR, VGPR or PR after bortezomib therapy failed to show an improvement in PFS and OS after ASCT. In contrast, post-transplant responses markedly influenced the outcomes after ASCT; patients achieving either CR or ≥VGPR had significantly longer PFS (P=.001 and .035, respectively) and OS (P=.002 and .002, respectively) compared to those without CR or ≥VGPR. Post-transplant maintenance treatment was not associated with improved PFS and OS in this cohort. Our data suggest that the response to bortezomib induction therapy could not predict outcome after ASCT. Achieving post-transplant CR or ≥VGPR is critical for prolongation of PFS and OS. Disclosures: No relevant conflicts of interest to declare.

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