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.

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 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.

First Line Therapy With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) In Patients With AL Amyloidosis and Potentially Reversible Contraindications To Autologous Stem Cell Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1985-1985 ◽  
Author(s):  
Giovanni Palladini ◽  
Paolo Milani ◽  
Marta Vidus Rosin ◽  
Andrea Foli ◽  
Giampaolo Merlini
Keyword(s):  
Stem Cell ◽  
Partial Response ◽  
Randomized Clinical Trials ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cardiac Response ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Second Line ◽  
Hematologic Response

Abstract Two recent reports by the Mayo Clinic and UK groups showed that the combination of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) grants a high rate of complete response (CR) and very good partial response (VGPR) in AL amyloidosis. In the two papers a total of 30 patients who received CyBorD upfront were reported, 63% of whom achieved CR. This combination has the further advantage of sparing stem cells, allowing second-line autologous stem cell transplant (ASCT). In the present study we treated with frontline CyBorD 56 consecutive newly diagnosed patients with AL amyloidosis, diagnosed between 2010 and 2012, who were transplant candidates and refused the procedure frontline or had potentially reversible contraindications to ASCT. Main exclusion criteria from the present study were age ≥70 years, NT-proBNP >8500 ng/L, systolic blood pressure <100 mmHg, and glomerular filtration rate (eGFR) <15 mL/min. The patients received weekly cyclophosphamide 300 mg/m2, bortezomib 1.3 mg/m2, and dexamethasone (40 mg). The dose of dexamethasone was reduced to 20 mg in 13 patients (23%) who were cardiac stage 3. Starting in September 2012, bortezomib was administered subcutaneously. Hematologic response was assessed every 2 cycles. Median age was 55 years. The kidney was involved in 41 patients (73%), the heart in 39 (70%), and the liver in 5 (9%). Cardiac stage was I in 17 patients (30%), II in 26 (46%), and III in 13 (33%). Five subjects (9%) had eGFR <30 mL/min. Eleven patients (20%) experienced severe adverse events, namely fluid retention and worsening heart failure (4, 7%), cytopenia (4, 7%), worsening renal failure (2, 4%), and deep venous thrombosis (1, 2%). Additionally, 4 patients (7%) died on treatment due to progressive cardiac amyloidosis, before the first evaluation of response. Overall, 63% of patients responded (95%CI: 49-75%). Best hematologic response by intent-to-treat, was CR in 16 patients (29%), VGPR in 8 (14%), and partial response (PR) in 11 (19%). All responders achieved at least PR by cycle 2, and best response was reached by cycle 6 in all cases. Cardiac response was achieved in 13/39 subjects (33%) and in 3/41 (7%) there was a renal response. So far, 10 patients, 6 non-responders, 3 attaining PR, and 1 in VGPR with progressing proteinuria were transplanted. Response data are available for 4 of these subjects, 3 of whom responded to ASCT (1 CR, 1 VGPR, 1 PR). With a median follow-up of living patients of 15 months, 11 patients (20%) died. Median survival was not reached and 78% of patients are projected to be alive at 1 year. The main baseline determinant of patients’ outcome was cardiac stage, with 100% 1-year survival in stage I, and 70% in stage II and III patients. This is the largest study on frontline CyBorD in AL amyloidosis reported so far. In this homogeneous patient population including low/intermediate-risk subjects with potentially reversible contraindication to ASCT, 43% of patients achieved CR/VGPR and cardiac dysfunction improved in one third of cases. Second-line ASCT was feasible in subjects with suboptimal responses. Though good, the response rate to CyBorD observed in the present study was lower than that reported in the 2 previously published studies, indicating that randomized clinical trials are needed to assess the efficacy of this combination in AL amyloidosis. Disclosures: Off Label Use: Bortezomib in AL amyloidosis. Merlini:Millennium-Takeda: Honoraria; Pfizer: Honoraria.

scholarly journals Is a severe and early neuropathy related to bortezomib? Is it related to the treatment response? 

2020 ◽  
Vol 8 (2) ◽  
pp. 19-21
Author(s):  
Maria Pereiro Sanchez ◽  
María Perfecta Fernández Gonzalez ◽  
María del Carmen López Doldán ◽  
Aurea María Gómez Marquez ◽  
José Luis Sastre Moral ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Treatment ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
White Male ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Lower Limbs ◽  
Bone Lesions ◽  
Cell Transplant

Myeloma is characterized by the neoplastic proliferation of a clone of plasma cells that invades the bone, causes destruction of the skeleton, and causes bone pain and fractures. In addition, other important features are anemia, hypercalcemia and renal failure. The standard treatment in Spain for autologous stem cell transplant (ASCT)-eligible patients is VTD (bortezomib, thalidomide, dexamethasone). Both bortezomib and thalidomide can cause or exacerbate an existing neuropathy. The mechanism by which they produce it is different in the two drugs.1 A 52-year-old white male was referred to our hospital for the evaluation of anemia (12 g/dL) and serum monoclonal protein (>4 g/dL). The diagnosis was a high cytogenetic risk MM stage R-ISS IIIA, without bone lesions. He only presented mild anemia. He started treatment with standard doses and in accordance to the usual protocol in a candidate patient for autologous stem cell transplant, based on a thalidomide and bortezomib scheme. On the 15th day of the 2nd cycle, the patient showed an autonomic neuropathy and an affectation of the deep sensibility, predominantly the vibratory and proprioceptive with generalized muscle weakness predominant in the lower limbs. He had no pain. He was totally dependent for the basic activities of daily life. Regarding the MM response, the patient showed a strict complete response. This case illustrates a young man with a high cytogenetic risk MM who developed an acute and early polyneuropathy grade IV after 1.5 cycles of standard treatment and with myeloma in strict complete response. The remarkable aspect about this case is the severe and early neuropathy, and an early, deep and persistent myeloma response. On some occasions this relationship has been reported, and we report an example of it.

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.

Outcomes and Treatments of Relapsed AL Amyloidosis Following Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1858-1858 ◽  
Author(s):  
Rahma Warsame ◽  
Soo-Mee Bang ◽  
Shaji K. Kumar ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Post Transplant

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.

Definition of a high-risk population among patients with AL amyloidosis not undergoing autologous stem cell transplantation using bone marrow plasmacytosis and the presence of CRAB.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8516-8516
Author(s):  
Taxiarchis Kourelis ◽  
Morie Gertz ◽  
Martha Lacy ◽  
Francis Buadi ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
High Risk Population ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Beta 2 Microglobulin

8516 Background: There is consensus that light chain amyloidosis (AL) patients with CRAB criteria (abnormal calcium or renal function, anemia or lytic bone lesions) also have multiple myeloma (MM). These patients are typically excluded from AL trials; however, AL patients with >= 10% bone marrow plasma cells (BMPC) in the absence of CRAB are included in trials along with AL with < 10% BMPC. We postulated that the currently used dichotomy may be incorrect and examined the spectrum of AL with and without MM. Methods: We identified 1,272 patients with AL seen within 90 days of diagnosis, between January 1, 2000, and December 31, 2010. We defined the population of patients with coexisting MM based on the existence of CRAB (AL-CRAB-MM). Patients without CRAB were divided into two groups, AL-only (<10% BMPC) and AL-PC-MM (>=10% BMPC). Results: Among the 1,272 patients, 117 (9%) had AL-CRAB-MM, 476 (37%) had AL-PC-MM, and 679 (53%) had AL only. Their respective median overall survivals (OS) were 16.2, 15.8, and 28.4 months (p<0.0001). Autologous stem cell transplant (ASCT) was performed in 203 (30%), 138 (29%) and 23 (20%) patients respectively. Since the outcomes of AL-CRAB-MM and AL-PC-MM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, AL-CRAB-MM and AL-PC-MM retained negative prognostic value independent of age, cardiac stage, prior autologous stem cell transplant (ASCT), beta 2 microglobulin, and dFLC. We next considered whether patients received ASCT as part of their treatment. For those patients who never received ASCT, the 5-year OS were 19%, 14%, and 31%, p<0.001, for AL-CRAB-MM, AL-PC-MM, and AL only respectively. In contrast, for those patients who received ASCT, the respective 5-year OS were 46%, 56%, and 73%, p<0.001. Conclusions: AL patients with >=10% BMPCs have a poor prognosis similar to patients with AL-CRAB-MM and should therefore be considered as AL with MM.

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]

Induction Therapy with Bortezomib and Dexamethasone Followed By Autologous Stem Cell Transplantation for Systemic Light Chain Amyloidosis: Our Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5907-5907
Author(s):  
Sandeep Jain ◽  
Luciano J Costa ◽  
Robert K Stuart ◽  
Saurabh Chhabra ◽  
Alice Mims ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cardiac Involvement ◽  
Stem Cell Transplant ◽  
Patient Characteristics ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
High Dose Melphalan

Abstract Introduction: The optimal treatment approach for systemic AL amyloidosis remains unclear. Autologous stem cell transplant (ASCT) is the only modality associated with long term survival, but failure to show survival benefit in randomized clinical trial raises doubts about its efficacy 1, 2. Outcomes after ASCT are better in patients who achieve complete hematologic response after the ASCT3. One report has shown improved outcomes with combining one dose of the proteasome inhibitor bortezomib with high dose melphalan as part of conditioning regimen 4. Preliminary data from a recent study suggest that the outcome of treating AL amyloidosis with two cycles of bortezomib and dexamethasone followed by ASCT was superior to the outcome of the ASCT alone5. We describe our experience with giving 4-6 cycles of bortezomib and dexamethasone induction prior to high dose melphalan and ASCT in patients with systemic AL amyloidosis. Patients and methods: We included all patients who underwent autologous transplant for symptomatic systemic AL amyloidosis at our institution from October 2010 till June 2014. Five patients were included in the analysis and patient characteristics are described in table 1. All patient received 4 -6 cycles of induction with bortezomib and dexamethasone followed by autologous stem cell transplant using high dose melphalan (200 mg/m2). One patient also received six cycles of lenalidomide and dexamethasone prior to bortezomib based induction for lack of response. Hematologic and organ response were assessed using the definitions from the 10th International symposium on Amyloid and Amyloidosis. Overall survival was calculated by Kaplan Meyer’s method using Graphpad Prism 6.0 software. Results: There was no transplant related mortality. After median follow up of 13 months (12-25 months) all patient are alive. Toxicities from the ASCT were mostly cytopenias in the immediate post-transplant period which were managed as per the standard of care. Two patients achieved hematological complete response while one more had very good partial response and other two achieved partial response. Of the four patients with nephrotic range proteinuria, two patients had > 95% reduction in proteinuria, one had > 75% reduction in proteinuria and another patient had > 50% reduction in proteinuria. One patient had Liver involvement with elevated alkaline phosphatase which normalized post-transplant (table 2). The responses were maintained on last follow up and none of the patient had hematological or organ relapses. Discussion: Bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, but its role in induction prior to high dose melphalan/ASCT to help achieve deeper hematological response is unknown. Our experience shows that this combination may be highly efficacious without significant toxicity. Limitations of our study include the small number of patients and absence of any patients with cardiac involvement, which is a worse prognostic marker. We conclude that the bortezomib and dexamethasone induction followed by high dose melphalan/ASCT for AL amyloidosis should be studied in prospective trials. Table 1.Patient Characteristics n=5Age, years 51.2 (44-62)Race (Caucasian)4 (80%)Gender ( female)3 (60%)Cardiac involvement 0 (0)Renal involvement 4 (80%)Serum creatinine ≥ 2.5 0 (0)Organ involvement ≥21 (20%)BM plasma cells > 10%1 (20%)Hgb ≤ 10 g/dl0 (0)LVEF <50%0 (0)Induction therapy Bortezomib/dexamethasone only4 (80%)Lenalidomide/dexamethasone + Bortezomib/dexamethasone1 (20%) Table 2. Outcomes n=5 Baseline After ASCT Hematologic response n=5 M protein 0.772 gm/dl 0.096 gm/dl 2 CR, 1 VGPR, 2 PR Renal response n=4 24 hours proteinuria 3.13 gm 0.432 gm 2 > 95% reduction, 1 >75% reduction, 1 >50 % reduction. Liver response n=1 Alkaline phosphatase 700 IU/L 62 IU/L Disclosures No relevant conflicts of interest to declare.

Improved Stem Cell Transplant Related Mortality for AL Amyloidosis At a Single Transplant Center

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2016-2016
Author(s):  
Zandra K. Klippel ◽  
Barry Storer ◽  
William I. Bensinger ◽  
Leona Holmberg ◽  
Pamela S Becker ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Risk Stratification ◽  
Research Funding ◽  
Cardiac Involvement ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Entire Cohort

Abstract Abstract 2016 The role of AHSCT in AL amyloidosis is controversial. There is evidence that AHSCT offers long term disease control with high organ response rates, however, the only randomized phase III trial comparing transplant with conventional melphalan and dexamethasone therapy deemed transplant inferior. Better understanding of risk stratification for SCT candidacy has resulted in TRM rates are as low as 5.6% in some series. The goal of the current study was to evaluate the TRM rate for all consecutive patients who have undergone AHSCT for AL amyloidosis at institution. Special attention in evaluation of any detectable differences in TRM over the time period of this review was a major goal of this project. Retrospective review was performed of all patients with primary AL amyloidosis who have undergone AHSCT at our institution. The database captured patients from December 2001 and our study includes patients through February 2012. Patients who were diagnosed with secondary amyloidosis by the stem cell transplant service and/or referring oncologist were excluded. TRM was defined as death from any cause within 100 days post stem cell infusion. We then evaluated data from the entire cohort and divided it into two different time periods: 2001–2006 and 2007–2012. Thirty-nine patients had an initial AHSCT during the study period. Nine patients were enrolled in the SWOG 0115 trial which comprised tandem autoSCT using 100 mg/m2 of melphalan conditioning 3–6 months apart. Of those, 6/9 (66%) had both transplants. For purposes of this abstract we report on the data resulting from first transplantation only for patients in the SWOG 0115 trial. The median age at transplant for the entire cohort was 57.6 years old (39–74). Males represent 64% of the patients. Most of the patients had symptomatic involvement of one organ (48.7%) with 23% having more than 2 organs involved. There were 14 patients transplanted in the 2001–2006 period and 25 patients in the 2007–2012 period. Overall TRM for 2001–2012 was 5.1%. During the 2001–2006 period TRM was 14% (2/14 patients). No TRM occurred for patients transplanted from 2007–2012. Overall survival (OS) improved when separately comparing the two study periods. Overall survival was 64% at 3 years in the 2001–2006 cohort and 92% at 3 years in the 2007–2012 cohort. Patients in the 2007–2012 cohort include all patients enrolled to SWOG 0115. Sixty percent of patients reported for that period received <200mg/m2 melphalan for transplant conditioning. Eight of nine patients enrolled in SWOG 0115 received 100 mg/m2, one received 140mg/m2. Six patients treated on our institution's standard amylodosis SCT protocol received 140mg/m2 conditioning. The remaining ten patients received 200mg/m2 melphalan. Patients in the 2007–2012 period were more likely to receive induction treatment prior to transplant with novel regimens (72% vs 21% p=0.003). In addition, these patients were more frequently diagnosed with amyloid cardiac involvement. For purposes of this abstract amyloid cardiac involvement is defined according to whether or not the SCT team concluded on the basis of history, physical examination and available ancillary data (including echocardiography) that the patient had amyloidotic cardiac disease (40% vs 14% p=0.15). All patients had echocardiography pre-AHSCT. The mean Inter Ventricular Septum (mIVS) thickness was 14.5 mm in the 2007–2012 period vs. 11.7 mm in the 2001–2006 one p=0.004. Univariate analysis of risk factors affecting improved OS identified year of transplant (>2006; p=0.03), number of treatments pre-transplant (>1; p=0.04), and time from diagnosis to transplant (>4mo; p=0.05) as factors associated with improved survival. Number of organs involved (>1; p=0.06) showed a trend towards worse survival. In conclusion, our single institution data demonstrates a reduction in TRM over the past 5 years. Reasons for improvement in TRM are under investigation and may include better risk stratification, better supportive care (including frequent hospitalization for cardiac monitoring in high-risk patients) and improvement in pre-AHSCT performance status for those patients receiving induction therapy with novel agents. Figure: Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Figure:. Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Disclosures: Holmberg: Millenium: Research Funding; Otsuka: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Sanofi: Research Funding.

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