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

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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Impact of Antithymocyte Globulin-Containing Conditioning Regimens on Patients Undergoing Allogeneic Stem Cell Transplantation for Progressive Myelodysplastic Syndrome: A Report From the SFGM-TC Group

Blood ◽

10.1182/blood.v118.21.3035.3035 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3035-3035

Author(s):

Ibrahim Yakoub-Agha ◽

Gandhi Damaj ◽

Marie Robin ◽

Stephane Vigouroux ◽

Alice Garnier ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cumulative Incidence ◽

Research Funding ◽

Acute Gvhd ◽

Conditioning Regimen ◽

Refractory Disease ◽

Advisory Committees ◽

Grade 3

Abstract Abstract 3035 Background: due to a risk of relapse of underlying disease in patients transplanted with progressive malignancy, the use of antithymocyte globulins (ATG), incorporated within the conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), is still controversial. We report here on a study of 245 consecutive patients transplanted between January 1999 and December 2009 in 26 French and Belgian centers for progressive MDS, defined as stable, untreated, relapsed or refractory disease. Patients and Methods: Inclusion criteria included patients aged over 18 who received allo-SCT from either a sibling (n=153) or HLA-A, -B, -C, -DRB1 and -DQB1 allele matched unrelated donor (10/10) (n=86) for MDS or AML/RAEB-t (with 20–30% BM blasts). Data quality was ensured using computerized discrepancy errors and vigorous on-site data verification of every single file. A qualified research technicien has been appointed by the University-Hospital of Lille to assist on-site centers that couldn't meet data quality requirements. HLA matching was double-checked by the French Bone Marrow Donor Registry. Results: The first 239 files analyzed until now are presented, including 154 males and 85 females. According to the WHO classification at diagnosis, 85 patients had RA/RARS/RCMD, 86 RAEB1, 62 REAB2 and 6 RAEB-t/AML. Sixty-six patients had progressed to a more advanced disease before allo-SCT. At diagnosis, 102 patients had an IPSS int-2 or higher. Cytogenetic IPSS was recorded as favorable (n=109), intermediate (n=61), unfavorable (n=63) and missing (n=6). Disease status at transplant was established as follows: relapsed or refractory disease (n=106) and untreated or stable disease without hematological improvement (n=133). Median age at transplantation was 53 years (range, 20–70). Patients received myeloablative conditioning (n=105) and nonmyeloablative (n=134) including busulfan-based regimens (n=127), TBI-based regimens (n=92) or other alkylating-agent-based regimens (n=20). In this series, 95 patients (40%) received ATG as part of conditioning ('ATG' group), whereas 144 did not ('no-ATG' group). The analysis reference date of April 1st 2011, median follow-up in survivors was 50 months (IQR, 33–92) with 59 patients having died of relapse and 77 of TRM. The estimated 3-year OS and EFS was respectively 42.3%, and 32.4%. The probability of relapse, overall and event-free survival at 3 years was not significantly different between the two groups. In contrast, the cumulative incidence of grade 2–4 acute GVHD was 48% in the no-ATG group and 30% ATG group (P <.001) and the cumulative incidence of grade 3–4 acute GVHD was 24% and 11% respectively (P <.001). Although the cumulative incidence of chronic GVHD was similar in the no-ATG and ATG groups (64% vs 46%, p=.15), a trend for a lower TRM was observed in the ATG group (22% vs 31%, p=.06). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of acute grade 2–4 [HR = 2.28, 95% CI: 1.39–3.74, p=.001] and grade 3–4 GVHD [HR = 2.19, 95% CI: 1.04–4.61, p=.035]. In conclusion, the addition of ATG to the conditioning regimen resulted in a decreased incidence of acute GVHD without increasing relapse rates and compromising patient survival undergoing allo-SCT for progressive MDS. Disclosures: Yakoub-Agha: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Fresinus: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Michallet:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Fresinus: Honoraria, Membership on an entity's Board of Directors or advisory committees. Deconinck:Celgene: Honoraria. Mohty:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.4356.4356 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4356-4356 ◽

Cited By ~ 1

Author(s):

Veronica Gonzalez De La Calle ◽

Eduardo Sobejano ◽

Julio Davila ◽

Enrique M Ocio ◽

Noemi Puig ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Research Funding ◽

B Lymphocyte ◽

Disease Stage ◽

Advisory Committees

Abstract BACKGROUND High dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old). Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT. AIMS The goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM). METHODS We reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression. RESULTS 106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%). Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03). Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007). CONCLUSIONS The lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. Disclosures Ocio: Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Incidence and Clinical Features of Extramedullary Multiple Myeloma in Patients Who Underwent Stem Cell Transplantation

Blood ◽

10.1182/blood.v124.21.5746.5746 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5746-5746

Author(s):

Matthew Weinstock ◽

Yosra Aljawai ◽

Irene M. Ghobrial ◽

Elizabeth A. Morgan ◽

Jacob P. Laubach ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Medical Center ◽

Academic Medical Center ◽

Advisory Committees ◽

Treatment Regimens

Abstract Background: Extramedullary disease (EMD), strictly defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow or adjacent soft tissue in a patient with underlying multiple myeloma, is an uncommon manifestation of multiple myeloma. Comparatively little is known about this disease entity, with no large case series published in the last decade. Patients and Methods: 663 consecutive patients with multiple myeloma who underwent autologous or allogeneic stem cell transplantation at a single, large, academic medical center in the United States from January 2005 to December 2011 were assessed for the presence or absence of EMD, as well as baseline demographic and biochemical characteristics, treatment regimens, and response to therapy. Results: A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8.3% of the total study population. Among the patients with EMD, 13 (23.6%) were found to have EMD at the time of initial presentation, while the remainder developed EMD during the course of their illness. Patients with EMD received a median of 5 different treatment regimens during the course of their illness, most commonly with combinations of dexamethasone, thalidomide, lenalidomide, and bortezomib, as well as autologous hemotopoietic stem cell transplantation. Patients had received a median of 3 lines of therapy prior to experiencing an extramedullary relapse. Patients with EMD had markedly elevated maximum serum LDH levels (median 613.5 units/L) and low minimum hemoglobin levels (median 7.8 g/dL). Common cytogenetic abnormalities included deletion 13q, deletion 11q, t(11;14), and deletion 17p. Available immunohistochemical data suggest that EMD specimens had frequent expression of CXCR4, CD44, and CD56. The median overall survival data of these patients was 3.2 years (range, 0.9-9.5) and the median time from diagnosis of EMD to death was 0.5 years (range, 0.002-3.2). Conclusions: This report describes a large series of multiple myeloma patients with EMD who were treated in the era of stem cell transplant at a single academic medical center. Further studies to examine the molecular characteristics of extramedullary multiple myeloma are necessary to better define this entity and characterize therapeutic options that can prolong survival in this otherwise very vulnerable population. Disclosures Ghobrial: Millennium/Takeda: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Laubach:Novartis: Research Funding; Onyx Pharmaceuticals: Research Funding. Schlossman:Millennium: Consultancy. Mitsiades:Millennium Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Research Funding; Johnson & Johnson: Research Funding; DFCI: patent submission on stromal co-culture technologies Patents & Royalties.

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Conditioning Regimen Intensity May Affect Outcome in MDS Patients Undergoing Allogeneic Stem Cell Transplantation, Depending on MDS Subgroup

Blood ◽

10.1182/blood-2019-130828 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5743-5743

Author(s):

Barry S. Skikne ◽

Anurag K. Singh ◽

Sunil Abhyankar ◽

Tara L. Lin ◽

Leyla Shune ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Research Funding ◽

Who Classification ◽

Conditioning Regimen ◽

Advisory Board ◽

Advisory Committees

Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for MDS. Besides the innate heterogeneity of MDS, intensity of the conditioning regimen (myeloablative (MAC) versus reduced intensity/non-myeloablative (RIC)), specific agents used in conditioning, donor and source of stem cells and GVHD prevention regimens further influence outcomes. We sought to determine how conditioning regimens influenced MDS subgroup cohort outcomes. We retrospectively analyzed outcomes of 107 MDS patients (63 male and 44 females) with median age 61.8 (17-73 years) who underwent allogeneic SCT at our institution between 2008 and 2017. For the purposes of this report, patients were grouped according to WHO classification into non-RAEB (RCMD, RA, RARS RCUD or 5q deletion, n=49) and RAEB (RAEB1 and RAEB2, n=58) categories. Median time from MDS diagnosis to transplantation was 139 days (20-3175). No patients were in complete remission (CR) at time of SCT. Allogeneic donor types were matched related, matched unrelated, haplo-identical and cord blood in 30, 65, 10 and 2 patients, respectively. Stem cell source was peripheral blood (91 patients) and bone marrow in 14. Forty patients (median age 52.2 (17-61) years) underwent MAC and 67 (median age 63.7 (23-73) years) RIC. Twelve patients died within 100 days of transplantation, 3 due to disease progression, 5 to acute GVHD, and 4 to other transplant-related causes. Median overall survival (OS) for all 107 patients was 1.3 years with 54%, 47% and 40% alive at 1, 2 and at 5 years. OS was slightly higher in patients undergoing RIC with OS of 57%, 48% and 40% (median 1.532 years) versus 50%, 40% and 38% with MAC (median 0.92 years) at the same time points (p>0.1). Median OS of the 49 patients with non-RAEB and 58 patients with RAEB MDS was 3.01 years versus 0.92 years (p>0.1). GVHD was the most frequent cause of death (46%), followed by relapse/progression (28%), infection (14%) and other (12%). Of 29 patients undergoing RIC with non-RAEB MDS, median OS was 3.78 years while for 38 RAEB patients it was 1.17 years (p>0.1). See table for OS according to conditioning regimen and WHO classification. For MAC, in 20 non-RAEB patients median OS was 2.2 years while the median OS was 0.69 years for 20 RAEB patients (p>0.1). CR after SCT was achieved in 57 patients (53%), 33 receiving RIC (CR 49.2%) and 24 receiving MAC (CR 60%). Seven patients subsequently relapsed, 4 RIC and 3 MAC. Of the non-RAEB patients achieving CR, median OS in the 16 patients treated with 111 RIC was not reached and in 14 patients receiving MAC, median OS was 3.75 years (p>0.1). For the 27 RAEB patients achieving CR, median OS was 4.4 years in 17 patients treated with RIC versus not reached in 10 patients treated with MAC. Overall, death in non-RAEB patients occurred in 26/49 (53%) compared to 38/58 (66%) RAEB patients and in 40/67 (59%) patients undergoing RIC versus 25/40 (63%) MAC patients (p>0.5). The hematopoietic transplant comorbidity index did not predict OS outcomes in these MDS patients (p>0.1) and the cytogenetic score according to the IPSS-R "very good -very poor" groups indicated no differences in OS in the non-RAEB patients but in RAEB patients significant differences according to the cytogenetic score was evident (P<0.01). Conclusions: In this retrospective analysis of MDS patients undergoing allogeneic SCT, achieving CR led to improved survival. In non-RAEB MDS patients achieving CR, OS was similar irrespective of conditioning intensity (RIC or MAC). Furthermore, outcomes did not differ in RAEB patients who achieved CR according to intensity of conditioning regimen. However, those receiving MAC had not reached median OS at 5 years. The outcomes in this analysis indicate that improvement in the incidence of deaths due to GVHD would likely have the greatest impact in improving survival in MDS patients undergoing allogeneic transplantation. Table Disclosures Abhyankar: Therakos: Other: Consulting, Speakers Bureau; Incyte: Speakers Bureau. Lin:Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Yacoub:Incyte: Consultancy, Speakers Bureau. Ganguly:Kite Pharma: Honoraria, Other: Advisory Board; Seattle Genetics: Speakers Bureau; Janssen: Honoraria, Other: Advisory Board; Daiichi Sankyo: Research Funding. McGuirk:Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation.

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Allogeneic Stem Cell Transplantation in First Chronic Phase CML during the Last Decade: Retrospective Analysis of the National SFGM-TC Registry

Blood ◽

10.1182/blood.v128.22.3476.3476 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3476-3476

Author(s):

Franck-Emmanuel Nicolini ◽

Valerie Coiteux ◽

Gerard Socie ◽

Didier Blaise ◽

Eric Deconinck ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Research Funding ◽

Conditioning Regimen ◽

Chronic Phase ◽

Advisory Committees ◽

Second Period

Abstract Background & aims The only curative treatment of CML to date, remains allogeneic stem cell transplantation (Allo-SCT) despite some observations of non-detectable disease recurrence after tyrosine kinase inhibitor (TKI) cessation. The scope of allogeneic stem cell transplant for chronic phase (CP-) CML remains debatable and it seems interesting to retrospectively analyse the settings of this procedure in such patients since the introduction of TKI within the therapeutic arsenal of this disease. Methods We retrospectively analysed the registry of the Francophone society of stem cell transplantation and cellular therapy (SFGM-TC) from 2002 to 2014, for patients being in CP at diagnosis and at transplant. All data were captured according to thefrench regulations and were collected after signed up informed consent for each patient. All patients were transplanted for different degrees of resistance or severe recurrent intolerance to TKI(s). We segmented the observation period into two parts: 2002-2006 (Imatinib era) and 2006-2014, once second generation TKI were available in our country (TKI2 era). All patients were in CP-CML at diagnosis and first chronic phase at transplant. Second transplants for the same patient were excluded from this analysis. Results From 2002 to 2014 the proportion of transplants for CML dramatically decreased form 7.1% to <3% of totalallo-SCT performed in the country. Nevertheless, between 2002 and 2014, 191 transplants were performed for CP-CML, 121 during the first period and 70 during the second period. Interestingly, age at transplant is 36 (26-43) for IM period and older, 44 (26-55) years for TKI2 period; with a sex ratio of 1.08 and 1.3 respectively (p=ns). The median interval between diagnosis and transplant was 19 (1.4-197) months for IM period and much longer thereafter[32 (6.6-194) months, p<0.001]. The source of cells varied a lot with 71% of BM, 25.5% PBSC and 3.5% CB for IM period, 37% BM, 56% PBSC and 7% CB for TKI2 period (p<0.001), whereas the proportion of MAC versus RIC remained stable (88.5%/11.5% versus 81%/19%, p=0.262). The use of TBI as a part of the conditioning regimen was drastically reduced during the second period: 37% IM era, 14% TKI2 era (p<001). While ABO match did not differ, the use of unrelated donors largely increased in the second period (66% versus 46%, p=0.015), with less identical sibling donors used (33% versus 52%) in this last period. The proportion of sex match did not differ with a majority of male to male transplants (28% and 37%; p=ns) performed in both groups. The majority of patients wereGratwohlscore 3 in IM period andGratwohlscore 4 in the second period. Overall, the cumulative incidence of grade 2-4 acute GVHD was 32%, 41.3% and 44% at 1,2 and 3 months respectively, and the overall cumulative incidence of chronic GVHD was 26%, 40%, 45%, 50% at 1, 2, 5, and 10 years. The TRM rates were not different between the 2 periods: 22.4%, 23%, 26.65% and 27.8% at 1, 2, 5 and 10 years for IM period and 16.2%, 19.7%, 22.4% and 27.8% at 1, 2, 5 years for TKI2 period (NR 10 year for this period, p=0.508).The overall (OS) and relapse-free survival (RFS) rates according to the two periods are shown in Figure 1, with only a trend in the improvement of OS and RFS in the TKI2 period (log-rank tests, p=0.601 and 0.651 respectively).Gratwohlscore efficiently segregated patients for OS (overall p value = 0.002) and RFS (p=0.007). Multivariate analysis adjusted on OS identified only age (HR=1.02, p=0.05), and a related donor as a favourable variable on outcome (HR=0.53, p=0.031) with no significant influence of age, interval diagnosis-allo-SCT, source of donor cells, and type of conditioning regimen. Conclusion Allo-SCT still remains a curative treatment of CP-CML despite significant toxicities over time and the picture of this procedure in the therapeutic arsenal has dramatically changed over the last decade due to multiple therapeutic options offered now. Despiteallo-SCT of patients with longer diseases histories, probably more co-morbidities, there is an encouraging trend in the improvement of OS and RFS. Figure 1 OS and RFS for CP-CML according to the engraftment period. Figure 1. OS and RFS for CP-CML according to the engraftment period. Figure 2 Figure 2. Disclosures Nicolini: BMS: Consultancy, Honoraria; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Coiteux:Novartis, BMS, ARIAD: Speakers Bureau. Michallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Peffault De Latour:Novartis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

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Depth of Response and Outcomes in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood-2018-99-116014 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4619-4619 ◽

Cited By ~ 1

Author(s):

Gunjan L. Shah ◽

Kenneth Seier ◽

Sean M Devlin ◽

David J. Chung ◽

Michael Scordo ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Partial Remission ◽

Research Funding ◽

Advisory Committees ◽

Depth Of Response

Abstract Background: For multiple myeloma (MM) patients, depth of response after induction therapy and after autologous hematopoietic stem cell transplantation (AHCT) has been shown to be important for progression free (PFS) and overall survival (OS) in some studies. Furthermore, the impact of minimal residual disease (MRD) on outcomes and treatment decisions has been widely discussed. We aimed to evaluate outcomes by depth of response after induction and AHCT. Methods: MM patients who received their first AHCT within 1 year of starting induction were identified from the institutional registry. MRD was assessed by non-10 color flow cytometry. Response was defined by the International Myeloma Working Group criteria. Summary statistics were used to describe the population. Kaplan-Meier methodology estimated PFS and OS by response status pre-AHCT and at post-AHCT restaging. Results: Between 2012 - 2014, 182 MM patients met our inclusion criteria, with 83% alive at last follow-up. The median age at AHCT was 60 years (range 29-76) with 57% male. By the International Staging System (ISS), 50% were stage I, 26% stage II, and 24% stage III. High risk cytogenetics were detected in 24%. Isotype was IgG in 55%, IgA 21%, Kappa Free Light Chain (KFLC) 11%, and lambda FLC (LFCL) 9%. First induction therapy included bortezomib in 90% and lenalidomide in 79%. Median time to AHCT was 5.5 months (range 2.8-11.7). The median follow-up from AHCT was 3.7 years (range 0.22 - 4.6 years), with 84% of patients receiving lenalidomide maintenance, and 9% receiving an additional autologous or allogenic transplant at relapse. Response prior to the initial AHCT was a complete remission (CR) in 13.7% (MRD negative 6.6%, positive 4.4%, unknown 2.7%), very good partial remission (VGPR) 38%, partial remission (PR) 40%, stable disease (SD) 5%, and progressive disease (PD) 4%. At post-AHCT restaging, responses had improved to 42% CR (MRD negative 23%, positive 6%, unknown 13%), 35% VGPR, 19% PR, 2% SD, and 3% PD. Median PFS from AHCT for the entire cohort was 3.2 years (95% CI 2.4 - 4 years) with 1-year and 3-year PFS 85% and 52%, respectively. Median OS was not reached (NR) (95% CI 4.4 years - NR) with 1-year and 3-year OS 97% and 88%, respectively (Figure 1). PFS from AHCT was significantly longer in patients with an MRD negative CR prior to AHCT with median PFS not reached (95% CI 1.7 - NR) compared to MRD positive/unknown CR, VGPR, and ≤ PR [3.64 years (95% CI 1.09-3.64), 3.46 years (95% CI 2.4 - NR), and 2.44 years (1.68-3.56 years), respectively, p=0.048] (Figure 2A). From post-AHCT restaging, PFS was also significantly longer in patients with an MRD negative CR prior to AHCT with median PFS not reached compared to MRD positive/unknown CR, VGPR, and ≤ PR [3.49 years (95% CI 0.86-3.49), 3.56 years (95% CI 2.5 - NR), and 2.4 years (1.6-3.33 years), respectively, p=0.026] (Figure 2B). However, there was no difference in PFS based on the post-AHCT restaging with median PFS in MRD negative CR, MRD positive/unknown CR, VGPR, and ≤ PR of 3.49 years (95% CI 2-NR), not reached (95% CI 1.4-NR), 2.96 years (95% CI 1.7-NR), and 2.86 years (95% CI 1.7 - NR) (p=0.78, Figure 2C), respectively. OS from AHCT was not significantly different by pre-AHCT response, and the median was not reached in any group (p=0.33, Figure 3A). Finally, the median OS from post-AHCT restaging by pre-AHCT response or by post-AHCT response was also not reached in any group (p=0.32 and 0.31, respectively; Figure 3B & C). Conclusion: For MM patients, AHCT deepened responses and increased the CR rate. We were unable to show a significant difference in outcomes at post AHCT restaging, which may be due to the effect of maintenance therapy, the small numbers of MRD negative patients, or the sensitivity of the MRD assay available during this time period, though potentially show that MRD positive patients do as well as MRD negative patients after AHCT. We plan to add additional patients treated in the more recent years who were assessed by more sensitive methods. Disclosures Shah: Janssen: Research Funding; Amgen: Research Funding. Korde:Amgen: Research Funding. Lesokhin:Janssen: Research Funding; Genentech: Research Funding; Takeda: Consultancy, Honoraria; Serametrix, inc.: Patents & Royalties: Royalties; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Squibb: Consultancy, Honoraria. Mailankody:Janssen: Research Funding; Physician Education Resource: Honoraria; Takeda: Research Funding; Juno: Research Funding. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Landgren:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

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Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽

10.1182/blood-2018-99-116496 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2149-2149

Author(s):

Romil Patel ◽

Neeraj Y Saini ◽

Ankur Varma ◽

Omar Hasan ◽

Qaiser Bashir ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Advisory Committees ◽

First Remission ◽

Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

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Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v118.21.3077.3077 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3077-3077

Author(s):

Sascha Dietrich ◽

Damien Roos-Weil ◽

Ariane Boumendil ◽

Emanuelle Polge ◽

Jian-Jian Luan ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Nk Cell ◽

Plasmacytoid Dendritic Cell ◽

Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

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The Effect of JAK 1/2 Inhibitors on Outcomes of Allogeneic Stem Cell Transplantation for Patients with Myelofibrosis

Blood ◽

10.1182/blood-2018-99-112769 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5784-5784

Author(s):

Guido Lancman ◽

Kathleen Miller ◽

Shuli Li ◽

Vincent T. Ho ◽

Amir T. Fathi ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Research Funding ◽

Acute Gvhd ◽

Advisory Committees ◽

Free Survival ◽

Donor Type

Abstract Introduction: Ruxolitinib was the first JAK 1/2 inhibitor (JAKi) approved for myelofibrosis (MF), with several other JAKi in development. Ruxolitinib was approved on the basis of reducing splenomegaly and improving constitutional symptoms, but its effect on subsequent allogeneic stem cell transplantation (SCT) is not well understood. Retrospective studies to date have reported mixed outcomes after SCT for MF patients with previous exposure to JAKi. In this multicenter retrospective study, we report on outcomes of patients with MF treated with SCT at our institutions. Methods: We analyzed outcomes for 184 consecutive patients at three institutions who underwent SCT for primary or secondary MF. Primary outcomes included overall survival (OS), progression free survival (PFS), and graft-versus-host-disease (GVHD)-free and relapse-free survival (GRFS), all measured from the time of SCT. Cox proportional hazard regressions were fit to estimate the association between the use of JAK 1/2 inhibitors prior to SCT and OS, PFS, and GRFS, adjusting for donor type and DIPSS-plus status. p<0.05 was considered statistically significant. Results: 72 patients received a JAKi prior to SCT, while 112 did not. Patients in these two groups were well-matched with respect to age, sex, DIPSS plus score, conditioning, and donor type (Table 1). Median follow-up was 31.2 months (range: 0.8-146.3 months). In univariate analysis, there was no difference in OS (JAKi: 4-yr OS 56.7% [95% CI 40.9-69.8%] vs. no JAKi: 43.6% [95% CI 32.9-53.9%], p=0.49), PFS (JAKi: 4 yr PFS 54.1% [95% CI 40.8-65.7%] vs. no JAKi: 43.9% [95% CI 33.4-53.9%], p=0.77), or GRFS (JAKi: 8-month GRFS 56.6% [95% CI 44.1-67.4%] vs. no JAKi: 50.4% [95% CI 40.4-59.5%], p=0.62) in the overall population; there was similarly no difference when comparing only intermediate-risk or only high-risk patients. In multivariate analysis, there was no difference in these outcomes for patients based on previous JAKi exposure when accounting for DIPSS plus score and donor type (related vs unrelated). Rates of acute GVHD were similar between the two groups (JAKi: 53.5% vs. no JAKi: 55.0%, p=0.88), including grade 3 or 4 acute GVHD (JAKi: 16.9% vs no JAKi: 19.8%, p=0.70). Conclusions: Our data suggest that there is no statistically significant difference in OS, PFS, GRFS, or rates of acute GVHD after SCT for MF patients based on previous JAKi treatment. This was true overall and after adjusting for DIPSS plus risk score or donor type. Given the retrospective design of our study, we were not able to assess prior response to JAKi or splenomegaly at SCT, which may influence outcomes. Given mixed results in the literature to date, we eagerly await the results of ongoing phase 2 trials of JAKi prior to SCT for MF. Disclosures Ho: Jazz Pharmaceuticals: Consultancy. Fathi:Astellas: Honoraria; Jazz: Honoraria; Boston Biomedical: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Agios: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria. Chen:Takeda Pharmaceuticals: Consultancy; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy; REGiMMUNE: Consultancy. Hoffman:Formation Biologics: Research Funding; Incyte: Research Funding; Janssen: Research Funding; Merus: Research Funding; Summer Road: Research Funding. Mascarenhas:Novartis: Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Promedior: Research Funding; Janssen: Research Funding; Roche: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Feasibility and Outcomes of T-Cell Depleted Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML and High Risk MDS

Blood ◽

10.1182/blood-2019-126211 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3324-3324

Author(s):

Satyajit Kosuri ◽

Sang Mee Lee ◽

Hongtao Liu ◽

Mylove Mortel ◽

Lucy A Godley ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Research Funding ◽

Advisory Committees

Background: Survival in patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) is dismal. Treatment options are limited; however, a proportion of these individuals can be rescued by allogeneic stem cell transplantation (allo-SCT). Historically, allo-SCT, especially for R/R myeloid diseases, has used myeloablative regimens and no T-cell depletion (TCD) to maximize graft-versus-leukemia effect, often restricting this approach to younger and fit pts with matched donors. The aim of this study was to investigate outcomes of in vivo T-cell depleted stem cell transplantation (TCD-SCT) in a high-risk AML and MDS population. Methods: We performed a retrospective analysis of 141 patients with R/R AML (n=108)/high risk MDS (RAEB or CMML, n=33) who received TCD-SCT at our center from 2002-2015. Median age was 55 years (18-71) with 37 (26%) pts older than 60. Patients underwent in vivo TCD with alemtuzumab or ATG and 117 (88%) received reduced-intensity conditioning (RIC). Alemtuzumab was generally given as 100 mg total divided over 5 days whereas rabbit ATG dosing included days -1, - 3, -5 (+/- on day -7). Alemtuzumab usually partnered with matched related (n=65; 46%) or unrelated (n=53; 38%) peripheral blood stem cell (PBSC) grafts whereas ATG mostly was a component of umbilical cord grafts combined with a CD34 selected haploidentical donor (haplo-cord) (n=23; 16%). Prognostic factors such as age, HCT-CI, CIBMTR score (Duval 2010), revised disease risk index (R-DRI), donor type and pre-transplant disease status were analyzed. Multivariate cox regression models were considered from forward selection for factors with a p value <0.1 in univariate analysis. Results: Table 1 summarizes baseline characteristics. Among the 141 R/R AML or high risk MDS pts, AML predominated (77%). Sixty six (47%) pts had primary induction failure (PIF), 42 (37%) had relapse and 33 (23%) had high risk MDS. Eighty three pts (59%) had peripheral blasts at time of TCD-SCT. Cumulative incidence (CI) of relapse for all pts was 53% and non-relapse mortality was 28% at 2 yrs. Two and 5 yr PFS rates for the group were 19% and 11%, respectively. Two and 5 yr OS rates for the group were 30% and 18%, respectively. Figure 1 shows OS by disease type. Day 100 mortality was 18%. Twenty one percent developed Grade 2-4 acute GVHD (aGVHD) (6% Grade 3-4), and only 5% developed chronic GVHD (cGVHD) requiring therapy. Figure 2 shows CI of cGVHD amongst disease types. Differences in 2yr survival outcomes were not significant among prognostic factors. Specifically, age 60+ vs younger was not prognostic (PFS 24% vs 17% p=0.4, OS 29% vs 29% p=0.7). Likewise, haplo-cord did not differ relative to matched donors in outcomes (PFS 18% vs 26% p=0.2, OS 35% vs 29% p=0.5). Conclusions: Although novel therapeutic approaches are emerging for R/R AML and high risk MDS, allo-SCT remains an established option for long-term disease control. In our analysis, outcomes after in vivo TCD-SCT in R/R AML and high-risk MDS pts treated with RIC mirror published historical results (Duval 2010, Schlenk 2010) but with low rates of cGVHD. The lack of significant difference in survival outcomes amongst age groups and donor sources suggests RIC with in vivo TCD can also be utilized as a platform in older individuals and those with alternative donors. With high relapse rates in this population, better pre-transplant disease reduction, minimal residual disease monitoring and post-transplant maintenance will be critical to increase long-term cures. Disclosures Liu: Agios: Honoraria; Arog: Other: PI of clinical trial; BMS: Research Funding; Karyopharm: Research Funding; Novartis: Other: PI of clinical trial. Larson:Novartis: Honoraria, Other: Contracts for clinical trials; Agios: Consultancy; Celgene: Consultancy. Odenike:Oncotherapy: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; Agios: Research Funding; CTI/Baxalta: Research Funding. Stock:Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Research to Practice: Honoraria. Kline:Merck: Honoraria; Merck: Research Funding. Riedell:Bayer: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Van Besien:Miltenyi Biotec: Research Funding. Bishop:Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Artz:Miltenyi: Research Funding.

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