Lenalidomide Maintenance Following Non Myeloablative Allogeneic Stem Cell Transplantation In Patients with Multiple Myeloma: Results of the HOVON 76 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3502-3502 ◽  
Author(s):  
Monique C. Minnema ◽  
Evelien Kneppers ◽  
Ronnie van Der Holt ◽  
Marie Jose Kersten ◽  
Sonja Zweegman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Late Onset ◽  
First Line ◽  
Grade 3

Abstract Abstract 3502 The phase II HOVON 76 study examined the efficacy and safety of maintenance treatment with lenalidomide 10 mgr daily for 21 days in a 28 day cycle for a maximum of 24 cycles following non T-cell depleted non myeloablative allogeneic stem cell transplantation (NMA allo-SCT). Patients with newly diagnosed Multiple Myeloma who had received autologous stem cell transplantation (auto-SCT) and had a HLA identical sibling could be included. The NMA allo-SCT was performed within 2–6 months after the auto-SCT after conditioning with TBI 2Gy only. Immunosuppression consisted of mycophenolate mofetil and ciclosporin. From January 2008 until March 2010, 35 patients from 5 academic hospitals were included. In that same time period 13 patients with NMA allo-SCT first line could not be included due to acute graft versus host disease (GvHD) ≥ grade 2 (8 pts), refusal (3 pts) or failing other inclusion criteria (2 pts). Of those 35 included patients 5 never started with lenalidomide because the study was put on hold and later stopped prematurely. Median age of the remaining 30 patients was 53 years (range 37–65). Patients started with lenalidomide median 12 weeks (range 4–27) after NMA allo-SCT. During lenalidomide treatment 19 patients (63%) developed acute (late onset) GvHD. GvHD started median 18 days (range 4–247) after start of lenalidomide, 12 of these 19 patients developed GvHD during cycle 1. In 11 patients GvHD resolved completely. Blood samples were taken for cellular analysis and will be reported. The total of maximal CTCAE grade 3 and 4 toxicities reported were 53% and 23%, respectively and consisted of blood/bone marrow toxicity grade 3 in 27% and grade 4 in 17%, metabolic/laboratory 23% and 7% and dermatology grade 3 in 10%. Lenalidomide stopping criteria were development of GvHD ≥ 2 and other toxicities CTCAE grade ≥ 3. Eight patients (27%) went off protocol treatment after 1 cycle, mainly due to the development of GvHD. After cycle 2 another 4 patients (13%) stopped treatment and after 4 cycles just 12 pts (40%) could continue. Only 3 patients have completed 24 cycles and 1 pt is still on protocol treatment. In 10 patients responses improved after start of lenalidomide; from PR to VGPR in 3, from PR to CR in 2 and from VGPR to CR in 5. Nine patients have progressed. Two patients have died; one patient with graft failure due to neutropenic fever and another due to progression. Median follow up is 69 weeks (2-122) and estimated 2 years OS is 93% and PFS 60%. In conclusion, early lenalidomide treatment following NMA allo-SCT is not feasible mainly due to the development of acute (late onset) GvHD. The occurrence of GvHD was closely related with the start of lenalidomide treatment. In this preliminary analysis no improvement of PFS was demonstrated compared to the HOVON 54 study in which no maintenance treatment after NMA allo-SCT was given. Disclosures: Minnema: Ortho Biotech: Speakers Bureau. Off Label Use: Lenalidomide is in the netherlands not registered for first-line use. Lokhorst:ortho biotech: Research Funding; celgene: Research Funding.

Secondary Primary Malignancies in Patients with Multiple Myeloma Treated with High-Dose Chemotherapy and Autologous Blood Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4087-4087 ◽  
Author(s):  
Roland Fenk ◽  
Florian Neubauer ◽  
Ingmar Bruns ◽  
Christian Saure ◽  
Thomas Schroeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Blood Stem Cell ◽  
Novel Agents ◽  
High Dose ◽  
Blood Stem Cell Transplantation

Abstract Abstract 4087 Introduction: Secondary primary malignancies (SPM) are an emerging issue in patients with multiple myeloma (MM) since the French IFM 99–02 trial has been closed as a consequence of a higher incidence of SPM in patients who had received lenalidomide as maintenance treatment compared to the patients in the placebo arm. Methods: To evaluate the incidence of SPM in the group of patients, who were treated with high-dose therapy (HDT) followed by autologous peripheral blood stem cell transplantation (PBSCT), we retrospectively looked at a homogeneous group of 313 consecutive patients, who were diagnosed with MM and had received HDT and autologous PBSCT at our hospital between December 1994 and January 2009. Induction treatment consisted of conventional chemotherapy without novel agents in 95% of patients and maintenance treatment was given with interferon or thalidomide in 37% und 35% of patients, respectively. Results: Within 313 patients with a median age of 55 (range: 31–74) years at diagnosis, we observed 18 (5.8%) patients who developed a SPM at various time points during the course of their disease. The number of patients who developed a solid neoplasm or a hematologic malignancy was identical. While the types of solid tumor observed varied greatly, we noted 8 patients with MDS/AML and only one patient with Hodgkins Disease. The median time from diagnosis of MM to the occurrence of SPM was 56 months (range: 14–127). The cumulative incidence of SPM was 19.7% with a rate of 0.7%, 5.8% and 15.7% at 2, 5 and 10 years after diagnosis without statistical differences between the group of patients with solid tumors (0.3%, 4.4%, 7.5%) and those with hematologic malignancies (0.4%, 1.8%, 9.3%). OS from the time of diagnosis in our group of 18 patients with SPM was not significantly different from that of patients without SPM with in median 70 and 83 months (p=0.7, HR 0.9 (0.5–1.7)), respectively. The same was true, when a landmark analysis was performed for patients alive after 2, 5 and 8 years with hazard ratios of 0.9 (95%CI 0.5–1.7, p=0.8), 0.6 (95%CI 0.3–1.4, p=0.2) and 1.0 (95%CI 0.2–4.3, p=1.0), respectively. In line with this finding, we found that survival time of more than 5 years from the time of diagnosis was the only prognostic parameter indicating a greater risk for the development of SPM (HR 4.7 (95%CI 1.1–19.8), p=0.04). In particular, we did not find any relationship to the incidence of SPM and the treatment with novel agents. The incidence rate of 206 patients, who were exposed to thalidomide was 6% (n=13, HR1.4 (95%CI 0.5–4.0), p=0.5), while of the 123 patients exposed to bortezomib 5 developed a SPM (4%, HR 0.4 (95%CI 0.1–1.1), p=0.1). There were two cases of SPM among the 71 patients following lenalidomide treatment (3%, HR 0.4 (95%CI 0.1–1.5), p=0.2). Having a closer look at the maintenance setting, which is associated with a longer duration of drug exposure, we did not find a higher incidence of SPM in patients treated with thalidomide maintenance after HDT in comparison to patients who had received interferon or no maintenance therapy (HR 1.0, 95%CI 0.3 – 3.2, p=1.0). Conclusions: In conclusion, the incidence of SPM in patients with MM treated with HDT is increased, especially for patients with a prolonged life span. SPM were not related to various treatment modalities including maintenance treatment with thalidomide. As a consequence on the available data, physicians should be aware of the risk of SPM and diagnostic measures to detect SPM should be included in the daily clinical workup of patients with MM. Disclosures: Fenk: Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy. Germing:Celgene: Consultancy, Research Funding. Gattermann:Celgene: Consultancy, Research Funding. Kobbe:Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy.

Lenalidomide as Salvage Therapy after Allogeneic Stem′Cell Transplantation in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3704-3704
Author(s):  
Friederike Lehmann ◽  
Jean El-Cheikh ◽  
Tatjana Zabelina ◽  
Francis Ayuk ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Dose Reduction ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Optimal Dose ◽  
Hematological Toxicity ◽  
Once Daily ◽  
Grade 3

Abstract Lenalidomide is an immunmodulatory drug, orally administered once daily, which is effective in relapsed multiple myeloma (MM). Here, we evaluated the efficacy and toxicity of lenalidomide in 24 MM patients with relapsed disease after allogeneic stem cell transplantation (allo-SCT). Median age was 59 (range, 37–70) years. The series included 8 females and 16 males. Prior to allo-SCT, all patients were heavily pretreated with a median of 6 chemotherapy cycles including autologous and allo-SCT in all patients. Also, prior to lenalidomide, salvage treatment included donor lymphocyte infusions (DLI) in 18 pts,, thalidomide in 11 pts and bortezomib in 13 pts. Lenalidomide was given at 15mg (n=4) or 25 mg (n=20) orally once daily on day 1–21 every 28 days and in 20 patients in combination with dexamethason.. No prophylactic anticoagulation was used. The median number of completed cycles was 5 (range 2–17). Myelotoxicity according NCI criteria was the primarily and major encountered side effect (leukopenia: 4% grade 4, 21% grade 3, 17% grade 2, thrombopenia: 17% grade 3, 29% grade 2) and led to dose reduction in 54% of the patients. Infectious complications were observed in 50%. Non-hematological toxicity consisted of cramps (n=9), fatique (n=5) and constipation (n=2). Thrombembolic complications (cerebral infarction) were observed in one patient, who received concomitant corticosteroid treatment for acute graft-vs.-host disease (GvHD), but neurological symptoms resolved completely. GvHD of the skin under lenalidomide treatment was seen in 3 patients (one grade 2, and 2 grade 1), with one case occurring shortly after an additional DLI.. Objective remission was achieved in 66% of the patients (CR: 8%, VGPR: 8%, PR: 50%) and stable disease (SD) in 13% of the patients, while in 21% progressive disease was noted. Prior treatment with thalidomide or with bortezomib did not influenced the rate of CR/PR. Surprisingly, patients with del 13q14 achieved a higher CR/PR rate than those without del 13q14 (p=0.02). The median time to progression was 9.7 months (95% CI: 7.5–11.9) and the median overall survival was 19.9 months (95% CI: 17.3–22.5). Lenalidomide is effective in relapsed patients with MM after allo-SCT. Major toxicity is myelotoxicity, which required dose reduction in the majority of patients. The optimal dose of lenalidomide after allo-SCT has to be investigated.

Secondary Monoclonal Gammopathy of Undetermined Significance after Allogeneic Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1238-1238
Author(s):  
Marian Schmitz ◽  
Henny Otten ◽  
Laurens Franssen ◽  
Suzanne van Dorp ◽  
Theo Strooisma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Protein Band ◽  
M Protein ◽  
Unrelated Donor

Abstract Background In the course of multiple myeloma (MM), patients may develop monoclonal bands of different isotypes than the original myeloma M-protein. Several terms have been used to describe this phenomenon, including abnormal protein band, oligoclonal protein bands, transient mono- or oligoclonal gammopathy, oligoclonal humoral response, atypical serum immunofixation pattern, and in myeloma patients, as we will use in this study, secondary MGUS (sMGUS). There are currently no data available regarding the frequency of sMGUS and its prognostic significance in MM patients who underwent allogeneic stem cell transplantation (allo-SCT). Here, we describe the occurrence of sMGUS and its association with response, progression-free survival (PFS), and overall survival (OS) in this group of patients. Study design We included a total of 138 patients who underwent 139 allo-SCTs (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma). All patients received their allo-SCT in the University Medical Center Utrecht. Secondary MGUS was defined as appearance of a protein band on immunofixation or electrophoresis that is different from the original myeloma M-protein in heavy-chain or light-chain isotype, or in its migration pattern. Results Sixty-seven (48.2%) patients developed at least one sMGUS after allo-SCT with a median latency of 6.9 months. Twenty-five patients had only one new protein band (18.0%), 9 (6.5%) had 2 bands, 8 (5.8%) had 3 bands, and 25 (18.0%) had four or more. The median duration of all sMGUS cases was 4.47 months (range 0.0-74.5 months). There was no progression of sMGUS to MM or other lymphoproliferative diseases. Secondary MGUS occurred more often in patients who achieved at least very good partial response after allo-SCT, compared to partial response or less (54.8% vs 26.5%, P=0.005). The incidence was also higher in the upfront setting as compared to patients with relapsed disease (60.0% vs 40.5%; P=0.037), or with a sibling donor compared to matched unrelated donor (57.0% vs 36.7%, P=0.026), but less often after T cell depletion (39.3% vs 61.8%, P=0.025). Importantly, development of post-transplant MGUS as a time-dependent variable, independently predicted for superior PFS and OS (median PFS: 37.5 vs 6.3 months, P<0.001; median OS: 115.3 vs 31.0 months, P=0.004). Since most TRM occurred in the first 6 months after allo-SCT (12 out of 15 TRM cases; 80%), we also performed a landmark analysis at this time-point. PFS and OS remained significantly superior in patients with sMGUS (n=100 patients; median PFS: 31.5 vs 4.9 months, P<0.001; median OS: 109.3 vs 57.3 months, P=0.015). Importantly, development of sMGUS was associated with improved PFS and OS both in patients who received allo-SCT as part of first-line treatment and in patients with relapsed MM. In addition, emergence of sMGUS predicted for enhanced PFS and OS in patients who achieved at least VGPR and also in patients who achieved less than VGPR after allo-SCT. Conclusions This is the first study that evaluates the significance of sMGUS in MM patients treated with allo-SCT. Development of sMGUS after allo-SCT was associated with a better quality of response, as well as significantly improved PFS and OS, both in patients transplanted in the upfront setting and at the time of relapse. Clinicians should be aware of the benign nature of this phenomenon, and sMGUS should not be confused with relapse or progression of disease. Disclosures Lokhorst: Celgene: Research Funding; J&J: Research Funding; Genmab: Research Funding. van de Donk:Celgene: Research Funding; J&J: Research Funding; Onyx: Research Funding.

Lenalidomide after Allogeneic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4840-4840 ◽  
Author(s):  
Friederike Lehmann ◽  
El-Cheikh Jean ◽  
Tatjana Zabelina ◽  
Francis Ayuk ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Dose Reduction ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hematological Toxicity ◽  
High Dose ◽  
Once Daily ◽  
Grade 3

Abstract Background: Lenalidomide is an immunmodulatory drug, orally administered once daily, which is effective in relapsed multiple myeloma (MM). Here, we evaluated the efficacy and toxicity of lenalidomide in 16 MM patients with relapsed disease after allogeneic stem cell transplantation (allo-SCT). Methods: Median age was 57 (range 37–68) years. The series included 5 females and 11 males. Prior to allo-SCT, all patients were heavily pretreated with multiple lines of chemotherapy, including high dose therapy with autologous stem cell support. Also, prior to lenalidomide treatment, other salvage therapies included donor lymphocyte infusions (DLI) in 93% of cases, thalidomide in 63%, and bortezomib in 88%. NCI-criteria were used to define toxicity. Lenalidomide was given 25 mg orally once daily on day 1–21 every 28 days. No prophylactic anticoagulation was used. Results: The overall median number of completed cycles was 5 (range 1–10). Very good partial response (VGPR) was achieved in 13%, partial remission (PR) in 53%, and stable disease (SD) in 27% of the patients. During the follow up period, disease progression was observed in 50% of cases, and death in one patient. The median progression-free survival was 8 months, while the median overall survival was not yet reached. Hematotoxicity was the primarily and major encountered side effect (leukopenia: 6% grade 4, 19% grade 3, 19% grade 2, 38% grade 1; thrombopenia: 19% grade 3, 19% grade 2, 31% grade 1). This myelotoxicity led to dose reduction (usually 10 mg) in 44% of the patients. Infectious complications were observed in 25%. Non-hematological toxicity was also seen in 75% of cases (56% grade 1, 19% grade 2), consisting of cramps in the leg, constipation, symptomatic fatigue, nausea and progressing polyneuropathy (n=1). Thrombembolic complications (cerebral infarction) were observed only in one patient, who was receiving concomitant corticosteroid treatment for acute graft-versus-host disease (GvHD), but neurological symptoms resolved completely. GvHD of the skin under lenalidomide treatment was seen in 25% of cases (one grade 2, and 3 grades 1), with one case occurring shortly after an additional DLI. Conclusions: Lenalidomide is effective in relapsed patients with MM after allo-SCT. Major toxicity is myelotoxicity, which required dose reduction in a majority of patients. With this background, a dose-finding study to determine the optimal lenalidomide dose as maintenance therapy after allo-SCT has already started.

First Interim Analysis of HOVON 76: Lenalidomide Maintenance Following Non Myeloablative Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2285-2285 ◽  
Author(s):  
Monique C. Minnema ◽  
Bronno van der Holt ◽  
Marie Jose Kersten ◽  
Sonja Zweegman ◽  
Ellen Meijer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Adverse Events ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Maintenance Treatment ◽  
Acute Gvhd ◽  
Bone Marrow Toxicity ◽  
Grade 3

Abstract Abstract 2285 Poster Board II-262 The phase II HOVON 76 study examines the efficacy and safety of maintenance treatment with lenalidomide 10 mgr daily for 21 days in a 28 day cycle for a maximum of 24 months following non myeloablative allogeneic stem cell transplantation (NMA allo-SCT). Patients with newly diagnosed Multiple Myeloma who had received intensive treatment including autologous stem cell transplantation (auto-SCT) and have a HLA identical sibling can be included. The NMA allo-SCT is performed within 2-6 months after the auto-SCT after a conditioning regimen of 2Gy total body irradiation. Immunosuppression consists of mycophenolate mofetil 15 mg/kg twice daily until day +84 and ciclosporin 4.5 mg/kg twice daily until day +120. Lenalidomide is started between 1 and 6 months after allo-SCT but preferably within 3 months. Before start the absolute neutrophil count must be ≥ 1.0 × 109/L and platelets ≥ 75 × 109/L. Acute graft versus host disease (GvHD) is an exclusion criterion to start with Lenalidomide except when affecting the skin for less than 50%. If during treatment acute GvHD grade II or higher develops Lenalidomide is stopped and only re-initiated at a lower dose level of 5 mgr once GvHD resolves within 2 months. Dose reduction is also applied in case of other CTCAE grade 3 or higher toxicities, including bone marrow suppression. As of January 2008, 31 patients have been included from 5 academic hospitals. Patients are predominantly male (68%) and median age is 53 years (range 32-65). Partial or complete treatment data are currently available from 24 patients. The total of maximal CTCAE grade 3 and 4 toxicities reported were 50% and 17%, respectively and consists of blood/bone marrow toxicity grade 3 in 29% and grade 4 in 13%, metabolic/laboratory 25% and 4% and dermatology grade 3 in 8%. Seven serious adverse events have been reported, consisting of acute GvHD of the liver in 3 patients, 1 acute GvHD of the intestines, 1 pleural effusion after start of prednisone treatment for skin GvHD, 1 EBV reactivation with fever and malaise, 1 fever of unknown origin. All patients are alive at this moment. After 1 cycle of Lenalidomide 6/24 patients (25%) went off protocol treatment mainly due to the development of acute GvHD (n=4), 1 because of progression and 1 refusal to continue. After cycle 2 another 4 patients (17%) went off protocol treatment due to adverse events and/or dose reductions below 5 mgr. Consequently only 58% of patients could continue with Lenalidomide maintenance after cycle 2. Of those patients, 2 went off protocol due to disease progression, 2 because of GvHD and 2 because of adverse events/dose reductions below 5 mgr after cycles 3-11. In conclusion, the most encountered toxicity with Lenalidomide maintenance treatment after NMA allo-SCT is bone marrow toxicity and acute GvHD. The incidence of GvHD is not higher than expected from our previous NMA allo-SCT study HOVON 54 without Lenalidomide treatment. Because of this toxicity only 58% of patients could continue with treatment after cycle 2. An update of the results with longer follow up will be presented. Disclosures: Off Label Use: lenalidomide is indicated for treatment of relapse multiple myeloma, in this study it is used as maintenance treatment after first line therapy.

scholarly journals Prospective Analysis of Bortezomib, Fludarabine and Melphalan As Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1020-1020
Author(s):  
Phyllis McKiernan ◽  
David S Siegel ◽  
David H. Vesole ◽  
Tracy Andrews ◽  
Noa Biran ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Significant Difference ◽  
Grade 3

Abstract Background: Despite advances in novel myeloma treatments and autologous hematopoietic stem cell transplantation (ASCT), allogeneic HSCT (alloSCT) remains the only curative option for patients (pts) with multiple myeloma (MM). Questions remain as to the timing of alloSCT, toxicity risks and optimal conditioning regimen. The addition of bortezomib (Vel) to fludarabine (Flu) and melphalan (Mel) for conditioning prior to alloSCT is based on the demonstrated safety of Vel in combination with melphalan prior to ASCT, the synergistic effect of Vel with Mel, and the ability of Vel to selectively eliminate allo-reactive T-cells. Methods: We present a prospective Phase II study using Flu/Mel/Vel (FMV) as a conditioning regimen for alloSCT. The primary endpoint is overall survival (OS), and secondary endpoints include progression free survival (PFS), incidence of graft-versus-host disease (GVHD) and transplant related mortality (TRM). For related donors, the conditioning regimen was Flu 30 mg/m2 days -5, -4, -3, -2, Vel 1.6 mg/m2 days -4, -1, Mel 140 mg/m2 day -2. For unrelated donors, rabbit ATG 4 mg/kg was given in divided doses days -3, -2, -1. GVHD prophylaxis consisted of methotrexate and tacrolimus. We compared pts receiving FMV to historical controls of pts receiving FM at the same dose and schedule without Vel. We also compared pts receiving FMV to all pts with MM treated with alloSCT including all regimens and donor types. The response criteria from the IMWG and M-Smart criteria were used to determine response and risk, respectively. Chi-square tests of association and Wilcoxon rank sum tests were performed to test for differences across groups. OS/PFS probabilities were calculated using the Kaplan-Meier product limit estimator with log rank-tests. Multivariate Cox proportional hazard models examined factors associated with OS/PFS. Results: Of the 54 pts who received FMV, 35 (65%) were male and the median age was 56 years. Twenty-seven pts had an HLA matched sibling donor and 27 had an unrelated donor. At the time of alloSCT, 5 pts were in a CR, 27 in a VGPR, 13 in a PR, 9 had < PR. Twenty eight pts (52%) had high risk disease. Twenty-nine pts (53%) received alloSCT as salvage, defined as relapsed or refractory to ASCT, and 25 pts (46%) as consolidation after ASCT. OS was 42% at 10 years. While 32 pts developed aGVHD, only 2 had ≥ Grade 3. Of the 31 pts who developed cGVHD, 23 were graded as extensive. TRM was 5% at day 100, and 15% over 10 years. Pts in the control groups had similar baseline characteristics to the FMV group. The only significant difference was 47 pts (72%) who received FM were transplanted as salvage, and 18 (28%) as consolidation after ASCT (p=0.035). The total number of pts who did not receive FMV (non FMV) was 121, with 66 pts receiving FM. Compared to pts who received FMV, there was no difference in OS for pts who received FM or the non FMV group, 35% (p=0.55) and 48% (p=0.855) respectively. There was no difference in pts who developed aGVHD, however 9 pts (13%) had ≥ grade 3 aGVHD in the FM group (p=0.004) and 15 (12%) in the non FMV group (p=0.006). The cumulative incidence of cGVHD was similar with 51% for pts receiving FM and 60% for FMV pts (p=0.32). TRM was similar to pts who had received FMV; 18% for FM and 17% for non FMV. There were no differences between the 3 groups across disease risk, donor type, or disease status at the time of alloSCT. Multivariate analysis of the 3 groups, shows achieving a CR after alloSCT (p=0.0006) or having cGVHD (p=0.0004) predicts for improved OS, while severe aGVHD (p=0.0002) predicts for decreased OS. Discussion: While FMV was associated with a lower incidence of severe aGVHD, the addition of bortezomib to the FM backbone did not improve PFS or OS. Day 100 TRM was low for all regimens, and the addition of Vel did not impact overall TRM. For all 175 pts, those who achieve a CR after alloSCT had a significantly improved OS. This prompts the question of whether strategies should be employed post alloSCT to maximize response to a CR, and the role of achieving MRD negativity after alloSCT also needs to be elucidated. Figure Figure. Disclosures Siegel: BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Biran:Amgen: Consultancy, Speakers Bureau; BMS: Research Funding; Merck: Research Funding; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Skarbnik:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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