scholarly journals Impact of Novel Agents on Frequency of Second Salvage Autologous Transplantation in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5832-5832
Author(s):  
Prajwol Pathak ◽  
Athira Unnikrishnan ◽  
Fei Zou ◽  
Helen Leather ◽  
Christopher R. Cogle ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Novel Agents ◽  
Optimal Timing ◽  
Relative Reduction ◽  
High Dose ◽  
Cell Transplant ◽  
Continuous Variables ◽  
Hematopoietic Stem

Abstract Introduction: High dose melphalan followed by autologous hematopoietic stem cell transplant (ASCT) is the standard of care in eligible multiple myeloma (MM) patients (pts). It is common practice to collect sufficient stem cells for two transplants, for the first ASCT immediately after induction, and for salvage ASCT following disease progression. We investigated the frequency of salvage second ASCT in the era of novel agents to determine if there has been a change in practice. Methods: We retrospectively reviewed medical records of MM pts who had stem cells collected for two ASCTs from 03/1996 to 12/2014. We then compared pts who received their first ASCT prior to January 2007 to those after this time. We excluded pts who received their second transplant as part of a clinical protocol, who received subsequent allogenic transplants, and pts who received 2 ASCT transplants as part of initial therapy. Fisher's exact test was used to assess significance of categorical independent variables and t-test was used to assess significance of continuous variables. Results: Forty of 506 pts (7.9%) received salvage second ASCT (Fig 1). Among 195 MM pts who received their first ASCT before 2007, 19 pts (9.7%) received salvage ASCT. After 2007, 21 of 311 MM pts (6.7%) received salvage ASCT (P= 0.24). When comparing salvage ASCT in the two time periods, no significant differences were noted, with the exception of a slightly lower KPS status (80% vs 70%, P=0.001), and the use of novel agents before the salvage therapy (0/19 (0%) vs 17/21 (81%), p <0.001). Otherwise the clinical characteristics, prior response and response duration, and initial stage were similar. Prior to 2007, 6 of 44 (14%) pts older than 65 years received salvage ASCT, whereas after 2007 only 3 of 110 (3%) patients received salvage ASCT (p = 0.017). Conclusions: Outside of clinical trials, the use of salvage second ASCT for relapsed MM is not frequent, and was noted to be decreasing further after 2007. We speculate that this 30% relative reduction in the frequency of salvage ASCT after 2007 is likely explained by the introduction of novel agents such as bortezomib and lenalidomde into the clinical practice, the use of maintenance therapy post-ASCT, and more non-ASCT options for salvage treatment after relapse. Further studies are needed to investigate the optimal timing for salvage ASCT and the patients who will best benefit from such treatment. Figure 1 Figure 1. Disclosures Wingard: Astellas: Consultancy; Gilead: Consultancy; Ansun: Consultancy; Fate Therapeutics: Consultancy; Merck: Consultancy.

The Optimal Timing for Stem Cell Collection After Induction Therapy for Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2252-2252
Author(s):  
Aziz Nazha ◽  
Dan T. Vogl ◽  
Una O'Doherty ◽  
Patricia Mangan ◽  
Kathleen Cunningham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Optimal Timing ◽  
High Dose ◽  
Cell Transplant ◽  
Cd 34 ◽  
The Mean ◽  
Stem Cell Collection

Abstract Abstract 2252 Introduction: High dose chemotherapy and stem cell transplant remains an integral part of the therapy for Multiple Myeloma patients under age of 70. The collection of sufficient number of stem cells for one or more transplant is however sometimes a challenge. Moreover, the optimal timing for stem cell collection after induction chemotherapies is controversial. The standard recommendation is for stem cell collection after 4–6 cycles of non-alkylator regimen, however studies to support this practice are limited. Material and Method: We conducted a retrospective analysis of 366 patients who were diagnosed with multiple myeloma and mobilized at the Hospital of University of Pennsylvania between January 2002 and December 2008. Patients who did not meet the initial inclusion criteria were those who had induction regimens containing an alkalytor agent or whose regimens were not well documented and were excluded from futher analysis (85). Every 4 cycles of any non-alkalytor agent was considered to be one treatment session for the purpose of this analysis. 245 patients received 1 or 2 treatment sessions and 36 received &gt; 2. All patients were mobilized with either Cyclophosphamide/G-CSF (CY/G-CSF), Plerixafor/G-CSF (AMD/G-CSF), or G-CSF alone. Result: The mean number of collected CD 34+ cells (CD 34+) was 9.22 × 106 CD34+/Kg in the patients who received 1 or 2 sessions and 6.87 × 1106 CD34+/Kg in the patients who received &gt; 2 sessions (P= 0.005). The number of the patients who collected &gt; 6 × 106 CD34+/Kg was 63%(153/246), 53%(19/36) respectively, (p= 0.005). The patients who mobilized with either CY/G-CSF or AMD/G-CSF collected higher number of CD34+ than the patients mobilized with G-CSF alone in both groups. (Table 1, 2.) The mean number of collected stem cells was 7.14 × 106 CD34+/Kg in the patients who received more than 2 sessions of different regimens and 6.26 × 106 CD34+/Kg in the patients who received &gt; 2 sessions of the same regimen. Conclusion: The patients who mobilized after fewer than 8 cycles of non-alkylator agents (2 sessions) collected a higher number of CD 34+ than those with greater than 8 cycles. CY/G-CSF or AMD/G-CSF are similar and superior to G-CSF alone in the more heavily treated patients. The patients who received multiple sessions of the same regimen have similar outcome compared to those who received multiple different regimens suggesting that the duration of the treatment may impact stem cell collection more than the content of the regimen. Prospective studies in this regards are warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Double-intensive therapy in high-risk multiple myeloma

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2827-2833 ◽  
Author(s):  
JL Harousseau ◽  
N Milpied ◽  
JP Laporte ◽  
P Collombat ◽  
T Facon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
High Risk ◽  
Autologous Transplantation ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
Dose Therapy ◽  
Group 2 ◽  
Group 1

A high remission rate is achieved with high-dose melphalan (HDM) in multiple myeloma (MM), and autologous transplantation of hematopoietic stem cells allows a prompt hematologic recovery after high-dose therapy. We treated 97 patients with high-risk MM (group 1:44 advanced MM including 14 primary resistances and 30 relapses; group 2: 53 newly diagnosed MM) with a first course of HDM. For responding patients a second course of high-dose therapy with hematopoietic stem cell support was proposed. After the first HDM, the overall response and complete remission rates were 71% and 25% with no significant difference between the two groups. The median durations of neutropenia and thrombocytopenia were significantly longer in group 1 (29.5 days and 32 days, respectively) than in group 2 (23 days and 17 days, respectively). This severe myelosuppression led to eight toxic deaths and the fact that only 38 of the 69 responders could proceed to the second course (three allogenic and 35 autologous transplantations). Among the 35 patients undergoing autologous transplantation (10 in group 1, 25 in group 2), 31 received their marrow unpurged collected after the first HDM, and four received peripheral blood stem cells. The median durations of neutropenia and thrombocytopenia after autologous transplantation were 24 days and 49 days, respectively. Two toxic deaths and nine prolonged thrombocytopenias were observed. The median survival for the 97 patients was 24 months (17 months in group 1, 37 months in group 2) and the median duration of response was 20 months. The only parameters that have a significant impact on the survival are the age (+/- 50 years) and the response to HDM. The median survival of the 35 patients undergoing autologous transplantation is 41 months, but the median duration of remission is 28 months with no plateau of the remission duration curve. Patients responding to HDM may have prolonged survival, but even a second course of high-dose therapy probably cannot eradicate the malignant clone.

scholarly journals Double-intensive therapy in high-risk multiple myeloma

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2827-2833 ◽  
Author(s):  
JL Harousseau ◽  
N Milpied ◽  
JP Laporte ◽  
P Collombat ◽  
T Facon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
High Risk ◽  
Autologous Transplantation ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
Dose Therapy ◽  
Group 2 ◽  
Group 1

Abstract A high remission rate is achieved with high-dose melphalan (HDM) in multiple myeloma (MM), and autologous transplantation of hematopoietic stem cells allows a prompt hematologic recovery after high-dose therapy. We treated 97 patients with high-risk MM (group 1:44 advanced MM including 14 primary resistances and 30 relapses; group 2: 53 newly diagnosed MM) with a first course of HDM. For responding patients a second course of high-dose therapy with hematopoietic stem cell support was proposed. After the first HDM, the overall response and complete remission rates were 71% and 25% with no significant difference between the two groups. The median durations of neutropenia and thrombocytopenia were significantly longer in group 1 (29.5 days and 32 days, respectively) than in group 2 (23 days and 17 days, respectively). This severe myelosuppression led to eight toxic deaths and the fact that only 38 of the 69 responders could proceed to the second course (three allogenic and 35 autologous transplantations). Among the 35 patients undergoing autologous transplantation (10 in group 1, 25 in group 2), 31 received their marrow unpurged collected after the first HDM, and four received peripheral blood stem cells. The median durations of neutropenia and thrombocytopenia after autologous transplantation were 24 days and 49 days, respectively. Two toxic deaths and nine prolonged thrombocytopenias were observed. The median survival for the 97 patients was 24 months (17 months in group 1, 37 months in group 2) and the median duration of response was 20 months. The only parameters that have a significant impact on the survival are the age (+/- 50 years) and the response to HDM. The median survival of the 35 patients undergoing autologous transplantation is 41 months, but the median duration of remission is 28 months with no plateau of the remission duration curve. Patients responding to HDM may have prolonged survival, but even a second course of high-dose therapy probably cannot eradicate the malignant clone.

Successful Salvage and Hematopoietic Reconstitution with Bortezomib and Melphalan in Relapsed and Refractory Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5209-5209
Author(s):  
Amitabha Mazumder ◽  
Sundar Jagannath ◽  
David H. Vesole
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Novel Agents ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Refractory Multiple Myeloma ◽  
Hematopoietic Reconstitution ◽  
Duration Of Response

Abstract The management of relapsed and refractory multiple myeloma (RRMM) patients who have failed older conventional and more recent novel agents remains challenging. Patients typically have short response duration, develop prolonged cytopenias and are usually not eligible for clinical trials due to inadequate bone marrow reserve. Furthermore, these patients often have inadequate numbers of stem cells (&lt;3 × 10(6) CD34/kg) remaining for a myeloablative transplant. In patients who have remaining stem cells in storage, we have developed an algorithm to enable the reconstitution of hematopopiesis to allow enrollment in clinical trials. In addition, our algorithm tests the synergy of bortezomib and non-myeloablative doses of melphalan with stem cell boost support. We have treated 6 patients with RRMM who have failed novel agents (including bortezomib) and chemotherapy (dexamethasone, cytoxan, etoposide, cisplatin, and doxil) and who have had limited duration of response previously with high dose melphalan. All patients were cytopenic (ANC &lt; 1000 and/or platelets &lt; 50,000/mcl) and thus not eligible for existing clinical trials. The melphalan was administered intravenously at 30–50 mg/m2 on days 1 and 4, dependent on the patient age and performance status. Bortezomib was administered 1.3 mg/m2 by intravenous push prior to the melphalan on the same schedule. The patients then received 1.5 to 2.2 × 10(6) CD34+ cells/kg. (depending upon the amount of remaining stem cells). All patients were treated in the outpatient clinic. 3 patients required hospitalization for neutropenic fever; the median hospitalization duration was 3 days (range 0 to 6). The overall response (MR, PR, VGPR) was 100% including: 5 PR and 1 VGPR.. More importantly, all patients achieved improved hematopoiesis with WBC &gt; 2000 and platelets &gt; 50,000/mcl. The median duration of response exceeded 2 months. All patients were able to proceed on to new clinical trials. We conclude that the combination of bortezomib and melphalan produces an effective salvage strategy, with hematopoietic reconstitution in RRMM. This non-myeloablative approach serves as a bridge for disease control and hematopoietic reconstitution to allow for subsequent eligibility on clinical trials. We recommend that during stem cell collection that sufficient hematopoietic stem cells be stored to support future myeloablative and similar non-myeloablative chemotherapy regimens.

scholarly journals The Evolution of Intracardiac Hemodynamics Post Autologous Stem Cell Transplant in a Case of Multiple Myeloma Associated with Severe Tricuspid and Mitral Valve Insufficiency

2017 ◽  
Vol 2 (s4) ◽  
pp. 45-47
Author(s):  
Cezara-Iuliana Tudor ◽  
Erzsébet Lázár ◽  
Marius-Vasile Găzdac ◽  
Annamária Pakucs ◽  
Eszter Mild ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Heart Function ◽  
Cell Transplant ◽  
Severe Condition ◽  
Hematopoietic Stem

AbstractStem cells are undifferentiated cells that can divide and become differentiated. Hematopoietic stem cells cannot transform into new stem cells such as cardiomyocytes or new heart valves, but they act through paracrine effects, by secreting cytokines and growth factors that lead to an increase in contractility and overall improved function. In this case report, we present how autologous stem cell transplantation can bring two major benefits: the first refers to hematological malignancy and the second is about the improvement of the heart condition. We present the case of a 60-year-old patient diagnosed with multiple myeloma suffering from a bi-valve severe condition in which autologous stem cell transplantation led to the remission of the patient’s malignant disease and also improved the heart function.

scholarly journals A complex of methods of radiation diagnostics in a patient with multiple myeloma (clinical case)

2020 ◽  
Vol 24 (4) ◽  
pp. 133-145
Author(s):  
E. V. Kryukov ◽  
V. N. Troyan ◽  
O. A. Rukavitsyn ◽  
S. A. Alekseev ◽  
S. I. Kurbanov ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Emission Tomography ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
X Ray ◽  
Positron Emission ◽  
Pet Ct

The article presents the possibilities of the complex application of methods of radiation diagnostics: bone x-ray, dual-energy X-ray absorptiometry, computed tomography, positron emission tomography combined with computed tomography using fluorodeoxyglucose labeled with 18-fluorine (PET/CT with 18F-FDG) in a patient with multiple myeloma, which was treated in the amount of high-dose therapy with autologous transplantation of hematopoietic stem cells. The diagnosis was established immunohistochemically. The use of these methods allowed us to dynamically assess the pathological changes characteristic of multiple myeloma.

Moving Beyond Autologous Transplantation in Multiple Myeloma: Consolidation, Maintenance, Allogeneic Transplant, and Immune Therapy

2016 ◽  
pp. 210-221 ◽  
Author(s):  
Amrita Krishnan ◽  
Ravi Vij ◽  
Jesse Keller ◽  
Binod Dhakal ◽  
Parameswaran Hari
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
The Other ◽  
Novel Agents ◽  
Patient Specific ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Minimal Residual

For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses. Though the consolidation strategy remains largely confined to clinical trials, significant data support the efficacy of consolidation in improving the depth of response and outcomes. There are also increasing rates of minimal residual disease–negativity with additional consolidation therapy. On the other hand, maintenance with novel agents post-transplant is well established and has been shown to improve both progression-free and overall survival. Evolving paradigms in maintenance include the use of newer proteasome inhibitors, immunotherapy maintenance, and patient-specific maintenance—a concept that utilizes minimal residual disease as the primary driver of decisions regarding starting or continuing maintenance therapy. The other approach to overcome residual disease is immune therapeutic strategies. The demonstration of myeloma-specific alloimmunity from allogeneic transplantation is well established. More sophisticated and promising immune approaches include adoptive cellular therapies, tumor vaccines, and immune checkpoint manipulations. In the future, personalized minimal residual disease–driven treatment strategies following ASCT will help overcome the residual disease, restore multiple myeloma–specific immunity, and achieve sustained disease control while minimizing the risk of overtreatment.

scholarly journals Stem-cell transplantation in multiple myeloma: how far have we come?

2019 ◽  
Vol 10 ◽  
pp. 204062071988811 ◽  
Author(s):  
Cinnie Y. Soekojo ◽  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Phase Iii ◽  
Novel Agents ◽  
Optimal Timing ◽  
High Dose ◽  
Phase Iii Trials

High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) has historically been an essential part of multiple myeloma (MM) management since early studies demonstrated its efficacy in relapsed disease, and subsequent phase III trials demonstrated better responses and improved survival with this modality compared with standard chemotherapy. With further advances in the MM treatment landscape, including the development of potent novel agents, there has been an increasing debate around various aspects of ASCT, including the optimal timing, role of single versus tandem ASCT, and the practice of consolidation and maintenance therapy post-ASCT. Routine incorporation of the novel agents at each of the treatment phases, induction, consolidation when used, and maintenance has led to better responses as reflected by increasing rates of minimal residual disease (MRD) negativity, longer progression-free survival (PFS) with improvement in overall survival (OS) and in some of the trials. The phase III trials over the last decade have provided significant clarity on the current approach, and have raised important questions regarding the applicability of this modality in all patients. This review aims to summarize the latest literature in the field and discusses how these findings impact the practice of ASCT today.

Reapplication of High-Dose Chemotherapy with Melphalan Followed by Autologous Hematopoietic Stem Cell Transplantation as Salvage Therapy for Patients with Relapsed Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3568-3568
Author(s):  
Leopold Sellner ◽  
Sonja Teodorov ◽  
Christiane Heiss ◽  
Axel Benner ◽  
Gerlinde Egerer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Time To Progression ◽  
Hematopoietic Stem ◽  
One Year

Abstract Abstract 3568 Introduction: High dose chemotherapy with melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT) is a standard treatment regimen for young patients with multiple myeloma. However, there are few studies, mainly with low patient counts, testing the benefit of the reapplication of high dose chemo therapy in relapsed or refractory myeloma. Methods: Here we retrospectively analyzed 178 patients (56% male, 44% female, median age 60 years) with relapsed or refractory myeloma who were treated by reapplying high dose chemotherapy with melphalan followed by autologous PBSCT in our institution over the last 18 years. The median follow up of this study was 54 months. Result: Median progression free survival (PFS) and overall survival (OS) after relapse autologous transplantation were 16 and 35 months, respectively. 66% of the patients received newer antimyeloma agents for reinduction therapy (39% thalidomide, 6% bortezomib, 21% lenalidomide). In univariate analysis, time between first transplantation and progression of disease had a significant impact on PFS and OS (p=0.001 and p<0.001). Estimated hazard ratio (HR) for prolongation of time to progression (TTP) after first transplantation of one year for PFS and OS are 0.85 and 0.73, respectively. The effect of TTP after first PBSCT on PFS and OS with respect to different clinically relevant cutoff values is illustrated in Table 1. Conclusion: Reapplication of high dose chemotherapy can be an effective treatment option for relapsed or refractory myeloma, in particular in patients with a time to progression after first autologous transplantation of more than one year. Disclosures: No relevant conflicts of interest to declare.

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