Pilot Study with Lenalidomide in Patients with POEMS Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4612-4612
Author(s):  
Andrea Nozza ◽  
Fabrizia Terenghi ◽  
Rita Mazza ◽  
Eduardo Nobile Orazio ◽  
Fausto Adami ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Clinical Manifestations ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Neurological Improvement

Abstract Abstract 4612 Introduction: POEMS syndrome is a rare multisystemic disease. Vascular endothelial growth factor (VEGF) correlates with the activity of the disease and it could account for clinical manifestations. Actually no controlled trials are available and there is no clear evidence for a standard therapeutic approach. Lenalidomide has anti-angiogenic activity through inhibition of VEGF and TNF alpha The aim of this study is to evaluate efficacy and safety of Lenalidomide in POEMS syndrome. Patients & method: From 10/09, we started a pilot study with Lenalidomide plus dexamethasone (RD) in pretreated or newly diagnosed POEMS patients not eligible for transplant procedure. Lenalidomide 25 mg/day was given for 21 days in association with weekly dexamethasone 40 mg until toxicity or progression occurred. After 6 cycles, pts were evaluated for response. Utonow 10pts have been enrolled, 9 men and 1 woman; median age was 51 years (range 45–76). All pts were pretreated and 2 pts had previously received high-dose melphalan with peripheral blood stem cell transplant. Monoclonal component (MC) was detected in all pts: IgAl in 3 pts, IgG l in 6 pts, l light chain in 1; all pts had sensory/motor peripheral neuropathy. Sclerotic bone lesions were detected in 5 pts, endocrinopathies in 8 pts, skin changes in 8 pts, peripheral edema in 8 pts, organomegaly in 7 pts, lymphoadenophaty in 3 pts, papilledema in 7 pts, thrombocytosis in 3 pts. VEGF serum level was elevated in all patient with a median value of 3544 pg/ml (range 1430–9788). Results: Seven pts are still on treatment with a median of 10 RD cycles (range 5–18). Six pts are evaluable for response after 6 cycles. A clinical response, with improvement of all disease manifestations, was observed in all pts. Neurological improvement was observed after 3 RD cycles, and was confirmed by nerve conduction studies after 6 cycles. One patient with tetraparesis is currently able to walk and his upper limb strength is normal with improved sensory neuropathy. MC disappeared in 2 patients. VEGF levels decreased in all pts: from a median of 3544 pg/ml (range 1430–9788) before treatment to 1539 pg/ml (467-3579) after 6 cycles. Three pts discontinued treatment: 1 withdrew consensus, 1 dropped out after 4 cycles for progression and 1 died for pulmonary infection on cycle 1. Dexamethasone dose adjustment was necessary in 5 pts and lenalidomide in 2 pts, (1 extraematological toxicity and 11 thrombocytopenia). Conclusions: This preliminary analysis,although in a limited series, highlights efficacy and safety of Lenalidomide in POEMS. Noteworthy the neurological improvement has been rapid and continuous, also in heavily pre-treated pts. At this time no patients experienced disease progression. A clear relationship between response and VEGF level was confirmed. The study accrual is ongoing. Disclosures: Off Label Use: Bortezomib and Thalidomide as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation in newly diagnosed multiple myeloma.

scholarly journals Utilization of Autologous Stem Cell Transplantation in Older Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5701-5701
Author(s):  
Justin King ◽  
Mark A. Fiala ◽  
Scott R. Goldsmith ◽  
Keith E. Stockerl-Goldstein ◽  
Mark A. Schroeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Older Patients ◽  
Research Funding ◽  
Small Sample ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Equity Ownership

Historically, high-dose therapy in combination with autologous stem cell transplants (ASCT) for multiple myeloma (MM) was reserved for younger patients. In more recent years, the use of ASCT has expanded in the older population. However, there is still limited data on the utilization and efficacy of ASCT in older patients, particularly those over the age of 75. To further evaluate this issue, we retrospectively analyzed all patients with newly diagnosed MM between the ages of 75-78, the institutional cutoff for ASCT eligibility, that were referred to the stem cell transplant unit at our institution for consultation from the years 2012-2018. Baseline characteristics, anti-myeloma treatments, and patient outcomes were abstracted through chart review. Seventy-five patients were referred to our institution. 71% were male, 29% female. 39% patients were considered ineligible for ASCT by the consulting transplant physician. Most patients were considered transplant ineligible due to comorbidities or poor performance status. Of the 46 patients eligible for ASCT, 52% underwent the procedure during their first-line therapy. The majority of those patients received reduced intensity melphalan (140 mg/m2) while 2 patients received conventional dosing (200 mg/m2). The other 22 patients eligible for ASCT declined or elected to defer the procedure and to be treated with conventional therapy. The characteristics of these three groups were similar and are detailed in Table 1. After a median follow-up of 30 months, 25% of the patients had expired. Estimated median overall survival (OS) was 71.3 months (unable to quantitate 95% CI) for all patients. Compared to transplant eligible patients, regardless of transplant receipt, those who were transplant ineligible had a 186% increase risk for death (HR 2.86; 95% CI 1.12-7.35; p = 0.029). There was also a notable trend for longer OS in those who underwent ASCT compared to those who were eligible but declined the procedure, but it was not statistically significant (HR 0.36; 95% CI 0.10-1.28; p = 0.114). At a transplant center, two-thirds of patients referred for newly diagnosed MM between the ages 75-78 were considered eligible for ASCT and one-third underwent the procedure. Outcomes were better for patients eligible for ASCT, regardless of whether they underwent the procedure. There was also a trend for better OS in patients who underwent the procedure compared to those who declined. While small sample sizes and the retrospective nature of the study limit our ability to draw conclusions, it appears that ASCT has an OS benefit among patients age 75-78. Disclosures Fiala: Incyte: Research Funding. Stockerl-Goldstein:AbbVie: Equity Ownership; Abbott: Equity Ownership. Vij:Genentech: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Wildes:Janssen: Research Funding; Carevive: Consultancy.

Phase II Study of Combination of the Hypercvad Regimen with Dasatinib in the Front Line Therapy of Patients with Philadelphia Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 837-837 ◽  
Author(s):  
Farhad Ravandi ◽  
Hagop M. Kantarjian ◽  
Deborah A. Thomas ◽  
Stefan Faderl ◽  
Dan Jones ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Allogeneic Stem Cell Transplant ◽  
Median Response ◽  
Platelet Recovery

Abstract Abstract 837 Background: Combination therapy with cytotoxic chemotherapy and tyrosine kinase inhibitors has improved the outcome for patients with Ph+ ALL with durable remissions in some patients even without an allogeneic stem cell transplant. The dual Src and Abl inhibitor dasatinib has ∼325 times more potent in vitro kinase inhibition than imatinib against BCR-ABL with significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Ph+ ALL. Aim: To determine the efficacy and safety of combining chemotherapy with dasatinib for treating patients with Ph+ ALL. Methods: In this phase II trial, patients with newly diagnosed Ph+ ALL receive dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in CR continue to receive maintenance dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Results: We have enrolled in the study 34 patients with untreated Ph+ ALL and 7 patients with 1 prior cycle of chemotherapy (before Ph+/BCR-ABL+ status was known). Patients younger than 50 years old have received a median of 6 cycles (range 2-8) and patients 50 years and older have received a median of 6 cycles (range 1-8). 20 patients are receiving maintenance in CR and two have completed the entire treatment regimen. Median age is 51 years (range 21 – 79); 22 patients were older than 50 years, Median WBC at diagnosis was 13.6 × 109/L (range, 1-276 × 109/L). 12 patients had CNS involvement at presentation. All patients are evaluable for assessment of response to induction; 39 (95%) achieved CR after first cycle or were CR at start. Two patients died before response assessment from infections. Thirty-one of 39 (79%) evaluable patients achieved cytogenetic (CG) CR after 1 cycle; 4 had a major CG response (3 had 5% and one had 15% Ph+), 2 had insufficient metaphases, and 2 are unknown (no CG exam on day 21 marrow). To date, 22 patients (56%) have achieved complete molecular remission (CMR) and another 8 (21%) have achieved a major (but not complete) molecular response (MMR) at a median of 14 weeks from initiation of treatment (range 2 – 59 weeks). Minimal residual disease assessment by flow cytometry is negative in 35 (90%) patients at a median of 3 weeks (range, 2-18 weeks). The median time to neutrophil and platelet recovery for cycle 1 is 18 and 23 days and for subsequent cycles is 15 and 20 days. Grade 3 and 4 adverse events have included bleeding (GI, GU, soft tissue and subdural hematomas)(18), pleural effusions (9), pericardial effusion (1), reversible rise in creatinine (10), deep vein thromboses (6), pulmonary emboli (3), as well as diarrhea, infections, hypophosphatemia, hypokalemia, hypocalcemia, hyperglycemia, and elevated transaminases. With a median follow up of 13 months (range 1-33), 29 patients (71%) are alive and 27 (66%) are in CR; 4 patients died in CR; 1 from an unrelated cardiac event and 3 from infections. Three patients have undergone an allogeneic stem cell transplant. The median disease free survival is 48+ weeks (range,1 to 140+) and the median overall survival is 52+ weeks (range, 3 to 143+). Eight patients have relapsed with a median response duration of 51 weeks (range 23-73) and 6 of them have died. In 5 patients morphological relapse was preceded by flow and molecular relapse. Five relapsed patients had ABL mutations (3 T315I, 1 F359V, and 1 V299L). Conclusion: Combination of chemotherapy with dasatinib is effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL. Disclosures: Ravandi: Bristol Myers Squibb: Honoraria, Research Funding. Kantarjian:Bristol Myers Squibb: Research Funding. Wierda:Genzyme: Research Funding; Genentech: Consultancy, Honoraria. Cortes:Bristol Myers Squibb: Research Funding. O'Brien:Bristol Myers Squibb: Research Funding.

Efficacy and Safety Of Treatments For Relapsed Or Refractory DLBCL: Results Of a Systematic Literature Review

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5104-5104 ◽  
Author(s):  
Ann Colosia ◽  
Peter C Trask ◽  
Robert Olivares ◽  
Shahnaz Khan ◽  
Adeline Abbe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Career Development Award

Abstract Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.

scholarly journals A Phase 2 Multi-Center, Open Label Study of Isatuximab Added to Standard Cybord Induction and Lenalidomide Maintenance Treatments in Newly Diagnosed, Transplant Eligible Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4767-4767
Author(s):  
Rami Kotb ◽  
Engin Gul ◽  
Donna E. Reece
Keyword(s):  
Stem Cell ◽  
Sample Size ◽  
Research Funding ◽  
Response Rate ◽  
Autologous Stem Cell Transplant ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
High Dose Melphalan

Abstract Background: Despite recent improvements, myeloma is still incurable. There is need to add new therapeutic tools. For young and fit patients, the current standard first-line therapy is a proteasome inhibitor (PI) containing induction, followed by stem cell collection, high dose Melphalan and autologous stem cell transplantation, followed by maintenance lenalidomide therapy in Canada. The anti-CD38 antibodies showed interesting activity in myeloma, and significant synergism with PI and IMiD based regimens. This CMRG-008 trial is designed to explore the benefit of adding Isatuximab to the current Canadian standard of care (CyBorD induction/Autologous SCT/Maintenance Len) in a single arm phase II trial. Design and Methods: Phase II study. Transplant eligible newly diagnosed myeloma patients (TE-NDMM) will receive Isatuximab added to four cycles of standard induction CyBorD chemotherapy (Cyclophosphamide 300 mg/m 2 PO, Bortezomib 1.5 mg/m 2 SC, and Dex 40 mg PO, all given on days 1, 8, 15 and 22 of 28-day cycles; Isatuximab 10 mg/kg IV days 1, 8, 15 and 22 of cycle 1; days 1 and 15 of cycles 2-4). After the completion of the induction treatment, subjects achieving at least stable disease will receive stem cell mobilization, collection of hematopoietic stem cells, high dose melphalan chemotherapy, and autologous stem cell transplantation. Maintenance treatment will start at 100 days (+/- 7 days) after the transplantation date (and to be continued until disease progression). The maintenance treatment will consist of Isatuximab administered in combination with Lenalidomide in 28-day cycles (Lenalidomide: 10 mg daily on days 1-21 of every cycle; Isatuximab: 10 mg/kg IV on days days 1, 8, 15 and 22 of cycle 1; days 1 & 15 of cycles 2-3; then day 1 of each subsequent cycle). The objectives: To evaluate the benefit of adding Isatuximab to CyBorD (induction = Isa + CyBorD) and Lenalidomide (maintenance = Isa + Lenalidomide) in transplant-eligible myeloma patients. Primary Endpoint: To determine the response rate (VGPR or better) defined by IMWG criteria at 100 days (+/- 7 days) after the autologous stem cell transplant (ASCT). Secondary Endpoints: A) To determine the response rate (VGPR or better) after induction treatment (before ASCT), and at 12 months, 24 months and 36 months. B) To evaluate additional efficacy outcomes including progression free survival (PFS), and overall survival (OS), time to response and duration of response. C) To confirm the feasibility, safety and tolerability of adding Isatuximab to CyBorD and to maintenance lenalidomide in transplant-eligible newly diagnosed myeloma patients. D) To determine the feasibility of autologous stem cell collection after Isa + CyBorD induction treatment. The key inclusion criteria are having a TE-NDMM with a measurable disease; adequate performance status; and adequate organ functions. The key exclusion criteria include previous exposure to anti-CD38 therapy, intolerance to CyBorD, adverse cardiac history, pulmonary disease, central nervous system disease, congenital or acquired immune suppression, and other concurrent severe or uncontrolled medical conditions. Statistics and Sample Size: Considering that the response rate (VGPR or better) after CyBorD induction therapy, high dose chemotherapy and autologous SCT is about 70-78%; and assuming a response rate (VGPR or better) to Isa-CyBorD induction and autologous stem cell transplant at 100 +/- 7 days of 88%; a sample size of 65 evaluable subjects will allow estimating the 95% confidence interval with a precision of +/- 7.9%. For the assumed rate and sample size, the lower bound of the confidence interval will be estimated to be larger than 80%. Assuming a 10% drop out rate, a total study size of 72 patients will be considered. This study is expected to open to recruitment in the third quarter of 2021. Clinicaltrials.gov #: NCT04786028. Disclosures Kotb: Janssen: Honoraria; Merck: Honoraria, Research Funding; Amgen: Honoraria; Akcea: Honoraria; Celgene: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria; Karyopharm: Current holder of individual stocks in a privately-held company. Reece: BMS: Honoraria, Research Funding; GSK: Honoraria; Karyopharm: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Millennium: Research Funding; Sanofi: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

Combination Therapy with BCNU/Etoposide/Melphalan (BEM) as Conditioning Regimen for Autologous Stem Cell Transplant In Multiple Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4587-4587
Author(s):  
Shanshan Liu ◽  
Ann Mohrbacher ◽  
Dan Douer ◽  
Vishesh R Kothary ◽  
Lisa Hanna ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
High Dose ◽  
Cell Transplant ◽  
Lytic Bone Lesions

Abstract Abstract 4587 Background: High-dose chemotherapy and autologous stem cell transplant (ASCT) remains an important therapeutic modality for MM patients. Traditionally high-dose single agent melphalan (200 mg/m2; Mel-200) has been used as the conditioning regimen prior to ASCT for MM. We investigated the combination regimen of BCNU, etoposide and melphalan (BEM) in this setting at our center. Methods: All patients who had undergone ASCT for MM utilizing BEM conditioning regimen at Norris Cancer Center, University of Southern California, Los Angeles were eligible. BEM consisted of BCNU 12 mg/kg (actual body weight or ideal body weight whichever was lower) iv on day -5, etoposide 60 mg/Kg iv on day -3, and melphalan 140 mg/m2 iv on day -1, prior to stem cell reinfusion on day 0. Overall survival (OS) was defined as time from MM diagnosis to death, or in patients still alive, the date of last follow-up. Progression-free survival (PFS) was defined as time from ASCT to date of relapse, or in patients without documented relapse, date of death or last follow up, whichever was sooner. Survival for patients with different clinical and disease-specific characteristics was explored using logrank test. Response was assessed according to International Uniform Response Criteria for MM. Results: A total of 44 MM patients underwent ASCT utilizing the BEM conditioning regimen. Of these, evaluable data was available for 42 patients (25 males; 60%, 17 females; 40%) with a median follow up of 27.6 mths. Median age at diagnosis was 54.5 yr (range 34–68) while median time from MM diagnosis to ASCT was 10.5 mths (range 2.8–47.8). MM subtypes included IgA (n=5, 12%), IgG (n=30, 71%) and light chain-only (n=7, 17%). Median bone marrow (BM) plasmacytosis at diagnosis was 42.5% (range 0%-100%). Durie-Salmon (DS) stages included stage I (12%), II (36%) and III (52%), while 4 patients (10%) had renal dysfunction at the time of initial MM diagnosis. Majority of the patients (71%) had lytic bone lesions at the time of diagnosis and 86% (n=36) hade secretory disease. Patients had received a median of 1 prior treatment (range 1–5), while 23 (55%) patients had received novel agents (proteasome inhibitors or IMiDs) prior to the BEM regimen. Response rates prior to and after the regimen are summarized in Table 1. After BEM-ASCT an additional 16 (38%) patients achieved a CR. Median duration of hospitalization and time to engraftment were 19 days (range 15–41) and 10.5 days (range 7–19), respectively. One patient died prior to discharge from the hospital post ASCT (Day 36 post ASCT) for a treatment related mortality of 2%. CR rate post BEM-ASCT was 64% with an ORR of 97%. Relapses have been noted in 25 patients to date. Median OS for all patients was 4.9 yrs (5.6 yrs for patients in CR and 6.6 yrs for patients in PR after BEM-ASCT). Median PFS was 23.9 mths for all patients (25 mths for patients in CR and 21.8 mths for those in PR after BEM-ASCT). No statistically significant differences were noted in OS based on patient gender (p=0.47), age at diagnosis (< or ≥60 yr), MM subtype (p=0.52), DS stage at diagnosis (0.09), patients without lytic bone lesions at diagnosis (p=0.054), secretor status (p=0.2), response status at the time of BEM-ASCT (p=0.9) or prior exposure to novel agents (p=0.62). Conclusions: BEM is a well-tolerated conditioning regimen prior to ASCT in MM and has efficacy comparable to Mel-200. BEM can be effectively employed in patients where Mel-200 is not feasible. We are particularly intrigued by its ability to deliver high CR rates (64%) compared to <30% (historical control). Very encouraging median OS (4.9 yr) and PFS (23.9 mth) rates were noted which were even better in patients who had a measurable response after this regimen. Further investigations will be needed to optimally define its potential as standard conditioning regimen in MM patients undergoing ASCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Induction with Bortezomib and Dexamethasone (BD) Followed By Risk Adapted High Dose Melphalan and Autologous Stem Cell Transplantation and BD Consolidation in Patients with AL Amyloidosis: A Phase II Feasibility Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3178-3178 ◽  
Author(s):  
Heather Landau ◽  
Nicole Montanez ◽  
Alexandra Cowan ◽  
Hoover Elizabeth ◽  
Carlos Flombaum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Treatment Initiation ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Weekly Schedule ◽  
Newly Diagnosed ◽  
Critical Determinant

Abstract Background: The depth and durability of hematologic response is a critical determinant of outcome in patients (pts) with light chain (AL) amyloidosis. Complete hematologic remissions (CR) following risk-adapted melphalan and stem cell transplant (RA-SCT) in pts with AL amyloidosis is associated with organ improvement and extended overall survival (OS). We have previously shown that using bortezomib and dexamethasone (BD) as consolidation following RA-SCT is associated with deeper hematologic responses and favorable outcomes. We have conducted a prospective phase II trial using BD as induction followed by RA-SCT and BD consolidation to determine the safety and hematologic and organ response rates of this treatment program for newly diagnosed, transplant-eligible pts with AL amyloidosis. Methods: Untreated pts with AL amyloidosis received 1-3 cycles of BD (B 1.3mg/m2, IV/SC, and D 40mg, IV/PO, days 1, 4, 8, 11). BD was discontinued before 3 cycles in patients who achieved CR. Pts were then assigned melphalan 100, 140 or 200mg/m2 based on age, renal function and cardiac involvement; Starting 3 months following RA-SCT, pts received six cycles of BD (B 1.3mg/m2, IV/SC and D 20mg, IV/PO days 1, 8, 15, 22) every 12 weeks as consolidation. Hematologic responses were assessed using International Society of Amyloidosis criteria (Palladini et al. JCO 2012) and organ responses using updated criteria (Palladini et al. Blood 2014), after induction, 3 months post RA-SCT, and at 12 and 24 months from treatment initiation. Patients with New York Heart Association Class III/IV heart failure, ECOG > 2 or > grade 2 neuropathy were ineligible. Results: Twenty pts, 70% male, with a median age of 60.1 years with renal (55%), cardiac (65%), liver/GI (15%) or nervous system (15%) involvement received BD induction and 18 patients have been transplanted. Two pts with cardiac disease died during BD induction (10% TRM); 85% of pts are alive with a median follow up of 28 mo. By intent to treat, 60% and 70% of patients achieved at least a very good partial response (>VGPR) following BD induction and RA-SCT, respectively. Overall, 95% of patients achieved hematologic responses (>PR) including 35% CR. Cardiac and renal responses were seen in 75% (N=8) and 60% (N=10) of evaluable pts at 1 year following treatment initiation. Most common grade >3 adverse events included GI (40%), Renal (30%), infectious (10%), and cardiovascular (10%); Grade 2 or higher neuropathy was seen in 40% of pts and warranted discontinuation of BD consolidation in 35% of pts. Conclusion: In newly diagnosed AL amyloidosis pts, BD induction followed by RA-SCT was safe and rapidly and effectively induced responses resulting in organ improvement. There was 10% TRM during BD induction and no deaths during transplant supporting the notion that early mortality in newly diagnosed AL pts is independent of treatment received. The high incidence of neuropathy may be related to the administration of BD on a twice weekly schedule and rendered some pts ineligible for post-transplant therapy. Whether transplant-eligible pts will ultimately derive more benefit from proteasome inhibitor induction versus consolidation is worthy of further study. Disclosures Landau: Spectrum Pharmaceuticals: Honoraria; Janssen: Consultancy; Janssen: Consultancy; Prothena: Consultancy, Honoraria; Takeda: Research Funding; Onyx: Honoraria, Research Funding. Landgren:Celgene: Honoraria; International Myeloma Foundation: Research Funding; BMJ Publishing: Consultancy; Onyx: Research Funding; Onyx: Consultancy; BMJ Publishing: Honoraria; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Medscape: Consultancy; Medscape: Honoraria; Bristol-Myers Squibb: Honoraria; Onyx: Honoraria. Giralt:TAKEDA: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding; SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding. Hassoun:Novartis: Consultancy; Takeda: Research Funding; Celgene: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees.

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