A Phase 1 Study of Bendamustine and Melphalan Conditioning for Autologous Stem Cell Transplant in Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2042-2042
Author(s):  
Tomer M Mark ◽  
Whitney Reid ◽  
Ruben Niesvizky ◽  
Usama Gergis ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplant ◽  
Phase 1 ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Phase 1 Study ◽  
Dose Levels

Abstract Abstract 2042 Background: Given data showing efficacy of bendamustine in treating multiple myeloma (MM), with the known toxicity profile significant for myelosuppression, we hypothesized that the addition of bendamustine to autologous stem cell transplant (ASCT) conditioning would enhance response without significant toxicity change. We now report the results of a phase 1 study of bendamustine + melphalan conditioning ASCT in MM. Methods: 21 patients were enrolled onto a 3+3 phase 1 study of bendamustine added to melphalan 200mg/m2 split on subsequent days at the following dose levels on the indicated days of melphalan: 1) 30 mg/m2 given on day 2; 2) 60 mg/m2 on day 2; 3) 90 mg/m2 on day 2; 4) 60mg/m2 on days 1 and 2; 5) 90 mg/m2 on day 1 and 60mg/m2 on day 2; 6) 125 mg/m2 on day 1 and 100mg/m2 on day 2. Stem cell infusion of > 2 million × 106 CD34+ cells/kg was performed at 24–48 hours after final chemotherapy. Patients received G-CSF with standard supportive care until engraftment, defined as absolute neutrophil count > 500/ml and a platelet count > 20,000/ml. Bone marrow biopsy and skeletal imaging were prior to and 100 days after ASCT to assess baseline and post-ASCT disease status. Disease response evaluation was performed monthly with immunoelectrophoresis and free light chain analysis in accordance with international uniform myeloma reporting criteria. Results: Twenty-one patients completed ASCT over 6 cohorts: 3 in dose level 1, 6 at dose level 2, and 3 each in dose levels 3, 4, 5, and 6. Median number of days (range) to wbc engraftment and platelet engraftment was 11 (9–13) and 12.5 (10–22), respectively. Toxicities were graded according to the Bearman scale. There was only one Grade 3 toxicity: a patient with respiratory decompensation in the setting of neutropenic fever in cohort 2 (a pulmonary dose limiting toxicity-DLT). Other toxicities noted in patients (%) (Grade 1 / Grade 2 respectively) were Cardiac: 6 (29%) / 2 (10%); Pulmonary 1 (5%) / 1 (5%); CNS 0 / 1 (5%); Stomatitis 15 (71%) / 0; GI 10 (48%) / 1 (5%). The CNS toxicity was narcotic-related psychosis. Eight patients had neutropenic fever, with 3 cases of bacteremia. No transplant-related mortality occurred. At present, there are 18 evaluable Day +100 myeloma responses: disease progression in 5 (24%), stable disease in 1 (6%), partial response 1 (6%), very good partial response in 2 (11%), and complete response in 9 (50%). Four patients (19%) died from MM, all with disease progression at 100 days post-ASCT, and all with pre-existing extramedullary disease. Summary: Bendamustine added to ASCT conditioning in MM does not exacerbate expected toxicities. The maximum tolerated dose of bendamustine in combination with melphalan 200mg/m2 was not found after a series of 6 treatment cohorts. The relatively high complete response rate and good regimen tolerability has prompted an extension phase 2 trial at the cohort 6 dosing to further evaluate regimen efficacy. Disclosures: Off Label Use: The study evaluates bendamustine safety in transplantation for myeloma; there is no FDA-label for this. Niesvizky:Merck: Research Funding.

scholarly journals Sequential response-driven bortezomib-based therapy followed by autologous stem cell transplant in AL amyloidosis

2020 ◽  
Vol 4 (17) ◽  
pp. 4175-4179
Author(s):  
Marco Basset ◽  
Paolo Milani ◽  
Mario Nuvolone ◽  
Francesca Benigna ◽  
Lara Rodigari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplant ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Survival Duration ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Duration Of Response ◽  
Landmark Analyses

Abstract Autologous stem cell transplant (ASCT) is highly effective in selected patients with light chain (AL) amyloidosis. Bortezomib, preceding or following ASCT, improves responses. Satisfactory responses, including at least a partial response, very good partial response (VGPR) with organ response, or complete response, can be observed after induction therapy alone. We report 139 patients treated upfront with cyclophosphamide/bortezomib/dexamethasone (CyBorD), followed by ASCT only if response was unsatisfactory. Only 1 treatment-related death was observed. After CyBorD, hematologic response (HR) rate was 68% (VGPR or better, 51%), with 45% satisfactory responses. Transplant was performed in 55 (40%) subjects and resulted in an 80% HR rate (65% ≥ VGPR). Five-year survival was 86% and 84% in patients treated with ASCT or CyBorD alone, respectively (P = .438). Also, 6- and 12- month landmark analyses did not show differences in survival. Duration of response was not different in the 2 groups (60 vs 49 months; P = .670). Twenty-one (15%) patients with an unsatisfactory response to CyBorD could not undergo ASCT because of ineligibility or refusal; instead, they received rescue chemotherapy, with HR in 38% of cases and 51% 5-year survival. This sequential response-driven approach, offering ASCT to patients who do not attain satisfactory response to upfront CyBorD, is very safe and effective in AL amyloidosis.

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1170-1170
Author(s):  
Rebecca L. Olin ◽  
David L. Porter ◽  
Selina M. Luger ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Response To Therapy ◽  
Cell Transplant ◽  
Significant Difference

Abstract Introduction: Autologous stem cell transplant (ASCT) as part of initial therapy has been shown to prolong survival of patients with multiple myeloma, with some achieving durable complete remission. However, the majority of patients ultimately relapse after ASCT and require salvage treatment. Options for the treatment of such patients have increased significantly over recent years, including not only novel chemotherapeutic and biological agents but also additional ASCTs. We performed a retrospective analysis of our experience with salvage ASCT for multiple myeloma to determine which clinical variables influence outcome. Methods: Between October 1992 and February 2005, we performed 342 ASCTs for multiple myeloma. Twenty-six of these were salvage transplants for relapsed disease after prior ASCT, and all were included in the analysis. Patients who received two planned (tandem) ASCTs were not included. Results: The median age at diagnosis was 47 (range 25–66), and median ISS and DS stages at diagnosis were 1 and 2, respectively. The initial ASCT was melphalan-based in 21/26; six (23%) achieved a complete response (CR) to the initial transplant, and fifteen (58%) achieved a partial response (PR). The median event-free survival (EFS) after the initial transplant was 19.5 months (range 2–60). The median time between initial and salvage ASCT was 2.6 years (range 0.3–7.6). Twenty-two patients (85%) received non-transplant therapy between ASCTs, and the median number of lines of therapy prior to salvage ASCT was 3. At the time of salvage ASCT, the median age was 52.5 (range 28–69). Fourteen patients received melphalan alone, eight received melphalan/TBI, and four received other regimens. Eleven patients (42%) achieved a response to therapy (1 CR, 10 PR). One patient (4%) died of transplant-related toxicity. The median follow-up after salvage ASCT is 12 months (range 0.2–58). Median EFS is 9 months, and median overall survival (OS) is 36 months. The 2-year EFS is 14%, and 2-year OS is 52%. On univariate analysis, both response to and EFS after initial transplant significantly predict improved EFS after salvage transplant (p=0.0008 and p=0.0065 respectively). Both also predict improved OS (p=0.03 and 0.0005 respectively). A greater than 12 month interval between first and second transplant also correlated with OS (p=0.04). There was no significant difference in EFS or OS by preparative regimen. Interestingly, type of response to the salvage transplant (CR/PR or less than PR) did not predict improved EFS or OS. Conclusion: This study suggests that salvage ASCT after relapse from initial ASCT is a feasible therapy for patients with heavily treated multiple myeloma, particularly those with a prolonged response to the first transplant.

Role of autologous stem cell transplant after induction therapy with bortezomib-lenolidomide or bortezomib-thalidomide in newly diagnosed multiple myeloma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8596-8596
Author(s):  
N. Shah ◽  
D. Weber ◽  
R. Orlowski ◽  
M. Wang ◽  
S. K. Thomas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Highly Active

8596 Background: The introduction of novel therapeutic options with bortezomib and immunomodulatory agents in the up-front management of multiple myeloma (MM) has significantly improved induction response rates. However, the role of high dose chemotherapy and autologous stem cell transplant (ASCT) after induction with these highly active agents is not known, especially in patients with only a partial response to induction therapy. Methods: We conducted a retrospective review of 95 newly diagnosed MM patients treated with induction bortezomib-lenolidomide-dexamethasone (BLD) or bortezomib-thalidomide-dexamethasone (BTD) prior to ASCT. Responses were graded according to IMWG criteria. Results: 19 patients received BLD and 76 patients received BTD. All patients were conditioned with a melphalan-based regimen. Of the 19 patients who underwent induction with BLD, complete response (CR), very good partial response (VGPR) and partial response (PR) were achieved in 2 (11%), 8 (42%) and 9 (47%) respectively for an overall response rate (ORR) of 19/19 (100%). After ASCT, CR, VGPR and PR were achieved in 9 (47%), 5 (26%) and 5 (26%) respectively for a continued ORR of 21/21 (100%). Notably, 4/8 (50%) of patients with a VGPR after induction therapy with BLD improved to a CR after ASCT. 3/9 (33%) of patients with an initial PR to BLD improved to a CR and 1/9 (11%) with a PR improved to VGPR after ASCT. Of the 76 patients who underwent induction with BTD, CR, VGPR and PR were achieved in 6 (8%), 37 (49%) and 31(41%) respectively for an ORR of 74/76 (97%). 1 patient had stable disease and 1 patient had progressive disease. After ASCT, 27/76 (36%) achieved a CR, 30/76 (39%) a VGPR and 18/76 (24%) a PR for an ORR of 75/76 (99%). Of the patients who initially had a VGPR to BTD 16/37 (43%) improved to a CR while 5/32(16%)of PR patients improved to a CR and 9/32 (28%) of PR patients improved to a VGPR. Conclusions: Of the 40 patients who only achieved a PR after induction therapy with BLD or BTD, 16 (40%) had further improvement to a CR or VGPR after ASCT. Thus there is a significant benefit of ASCT in these patients who initially demonstrate relative resistance to induction therapy with highly active regimens. [Table: see text]

scholarly journals Pericardial relapse of multiple myeloma

2020 ◽  
Vol 13 (4) ◽  
pp. e233340
Author(s):  
Lee S Jamison ◽  
Clifton Craig Mo ◽  
Mary Kwok
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Poor Prognosis ◽  
Stem Cell Transplant ◽  
Complete Response ◽  
Initial Therapy ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Extramedullary Relapse ◽  
To Receive

In patients who experience relapse of multiple myeloma, upwards of 30% can have extramedullary disease. The presence of extramedullary multiple myeloma is typically associated with adverse cytogenetics and a poor prognosis. Organs most commonly involved include the liver, skin, central nervous system, pleural effusions, kidney, lymph nodes, and pancreas. We present the case of a 53-year-old man with IgA kappa multiple myeloma with the adverse cytogenetic findings of t(4;14) and 1q21 gain who had achieved a stringent complete (sCR) response after initial therapy with carfilzomib, lenalidomide and dexamethasone. Stringent complete response is defined as the normalization of the free light chain ratio in the serum and an absence of clonal cells in the bone marrow in additiion to criteria needed to achieve complete response. Prior to undergoing a planned autologous stem cell transplant, this patient experienced cardiac tamponade secondary to extramedullary relapse of his multiple myeloma which was limited to the pericardium. In response, his treatment regimen was transitioned to pomalidomide, bortezomib, dexamethasone and cyclophosphamide for three cycles after which he again achieved sCR and ultimately underwent autologous stem cell transplant. Post-transplant consolidation therapy was administered in the form of pomalidomide, bortezomib and dexamethasone, followed by pomalidomide and bortezomib maintenance, which he has continued to receive for 3 years without evidence of disease progression.

scholarly journals Complete response after autologous stem cell transplant in multiple myeloma

2014 ◽  
Vol 3 (4) ◽  
pp. 939-946 ◽  
Author(s):  
Lalit Kumar ◽  
Nida Iqbal ◽  
Anjali Mookerjee ◽  
Rakesh Kumar Verma ◽  
Om D. Sharma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

scholarly journals A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma

2017 ◽  
Vol 52 (10) ◽  
pp. 1372-1377 ◽  
Author(s):  
A Dispenzieri ◽  
A D'Souza ◽  
M A Gertz ◽  
K Laumann ◽  
G Wiseman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Phase 1 ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Phase 1 Trial

Local Experience with Autologous Stem Cell Transplant in Multiple Myeloma at a Public Institution (Instituto Nacional de Cancerologia)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5504-5504
Author(s):  
Eduardo Cervera ◽  
Jorge Carlos Torres ◽  
Nidia P. Zapata ◽  
Juan Rafael Labardini ◽  
Jose Ramiro Espinoza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Complete Remission ◽  
Partial Response ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Autologous Stem Cell Transplant ◽  
Public Institution ◽  
Cell Transplant ◽  
Good Partial Response

Abstract Introduction. Autologous stem cell transplant is considered the standard of care in young (<70) fit patients with Multiple Myeloma. We know that intensive chemotherapy or stem cell transplant do not produce a cure, but it does prolong event free survival and overall survival. The aim of this study is to report 15 years of experience in stem cell transplant at the Multiple Myeloma (MM) clinic at Instituto Nacional de Cancerologia (INCan). This is a retrospective, observational trial, we reviewed clinical and electronic files of patients that received an autologous stem cell transplant between January 1st of 2005 and March 1 2015. We assessed clinical status, demographic variables, disease status and clinical outcome of the patients that were included in the study. 48 patients were included into the study, 25 males and 23 females, we grouped the patients according to age, <35 years (2 patients), <50 years (14 patients), 50-65 years (31 patients), >65 years (1 patient). 34 patients had a normal karyotype, 4 had 13q14, 2 had MLL deletion and 8 did not had a karyotype performed. According to the M component we had 6 IgA patients, 32 IgG, 1 IgM, 1 Kappa, 5 lambda, 2 non secretory and 1 combined. According to ISS, 34 patients were assigned a ISS of 1, 10 a SS of 2, and 4 a ISS of 3. The majority of our patients were transplanted within the first line of treatment, 2 within the second line and none with more than 2 lines of treatment. 20 patients that received thalidomide plus dexamethasone achieved complete remission prior to transplant. 14 patients received thalidomide plus dexamethasone achieved very good partial response. 4 patients that received bortezomib plus thalidomide or dexamethasone achieved complete remission prior to transplant. 4 patients received bortezomib plus thalidomide or dexamethasone achieved very good partial response prior to transplant. 3 patients that received two lines of treatment achieved complete remission prior to transplant. 3 patients achieved very good partial response prior to transplant and received more than two lines of treatment. Time from diagnosis to transplant had a mean time of 17.4 months, with 6-12 months as the most prevalent group with 20 patients, followed with 13 patients in the 12-24 months window. 17 tandem transplants were performed. From the 25 patients that received a ASCT and were in CR, 19 maintained that response, from the 23 patients that achieved VGPR 20 maintained that response, 1 achieved partial response (PR), 4 had stable disease, and 4 had progression of the disease. We are looking forward to presenting the full data of our analysis. Since our casuistry does not differ from the international reports. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma

2019 ◽  
Vol 3 (13) ◽  
pp. 2022-2034 ◽  
Author(s):  
Edward A. Stadtmauer ◽  
Thomas H. Faitg ◽  
Daniel E. Lowther ◽  
Ashraf Z. Badros ◽  
Karen Chagin ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Partial Response ◽  
Disease Progression ◽  
Stem Cell Transplant ◽  
Objective Response ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract This study in patients with relapsed, refractory, or high-risk multiple myeloma (MM) evaluated the safety and activity of autologous T cells engineered to express an affinity-enhanced T-cell receptor (TCR) that recognizes a peptide shared by cancer antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and L-antigen family member 1 (LAGE-1) and presented by HLA-A*02:01. T cells collected from 25 HLA-A*02:01-positive patients with MM expressing NY-ESO-1 and/or LAGE-1 were activated, transduced with self-inactivating lentiviral vector encoding the NY-ESO-1c259TCR, and expanded in culture. After myeloablation and autologous stem cell transplant (ASCT), all 25 patients received an infusion of up to 1 × 1010 NY-ESO-1 specific peptide enhanced affinity receptor (SPEAR) T cells. Objective response rate (International Myeloma Working Group consensus criteria) was 80% at day 42 (95% confidence interval [CI], 0.59-0.93), 76% at day 100 (95% CI, 0.55-0.91), and 44% at 1 year (95% CI, 0.24-0.65). At year 1, 13/25 patients were disease progression-free (52%); 11 were responders (1 stringent complete response, 1 complete response, 8 very good partial response, 1 partial response). Three patients remained disease progression-free at 38.6, 59.2, and 60.6 months post-NY-ESO-1 SPEAR T-cell infusion. Median progression-free survival was 13.5 months (range, 3.2-60.6 months); median overall survival was 35.1 months (range, 6.4-66.7 months). Infusions were well tolerated; cytokine release syndrome was not reported. No fatal serious adverse events occurred during study conduct. NY-ESO-1 SPEAR T cells expanded in vivo, trafficked to bone marrow, demonstrated persistence, and exhibited tumor antigen-directed functionality. In this MM patient population, NY-ESO-1 SPEAR T-cell therapy in the context of ASCT was associated with antitumor activity. This trial was registered at www.clinicaltrials.gov as #NCT01352286.

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