Outcomes of Anti-PD1 Treatment for Relapsed/Refractory Hodgkin Lymphoma: A German Hodgkin Study Group (GHSG) Multi-Center Real-World Analysis

Abstract Background: Immune-checkpoint inhibition with antibodies targeting programmed death protein 1 (PD1) was well tolerable and highly effective in pivotal phase II and III trials in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL). We aimed to evaluate emerging therapeutic sequences and the safety and efficacy of anti-PD1 antibodies in the rapidly changing routine care of r/r cHL. Methods: GHSG-affiliated hemato-oncology departments and practices in Germany were invited to participate in this retrospective study. Patients ≥18 years of age receiving anti-PD1 antibodies for r/r cHL in routine care were eligible. Patient, disease and treatment characteristics were documented by the treating physicians with standardized case report forms. Locally assessed response rates were reported as complete (CR) or partial (PR) remission, stable (SD) or progressive (PD) disease and summarized as objective response rate (ORR: CR + PR). Progression-free (PFS) and overall survival (OS) were analyzed according to Kaplan-Meier from the start of anti-PD1 treatment in routine care to PD (PFS) or death from any cause (PFS + OS). All analyses were done descriptively and conducted in SAS V9.4. Results: A total of 58 r/r cHL patients (pts.) with a median age of 48 years (range 19-89 years) and male predominance (57%) initiated anti-PD1 treatment between 11/2014 and 01/2021 at 15 sites. Median time from 1 st-line to anti-PD1 treatment was 5.5 years (0.8-26.0). The majority had received prior brentuximab vedotin (BV, 86%) or an autologous stem-cell transplantation (autoSCT, 62%) and 16% undergone prior alloSCT. Relevant co-morbidities including HIV, pre-existing autoimmune conditions, cardiovascular diseases and dialysis-dependent kidney failure were documented in 49% of patients. An impaired ECOG performance status of ≥1 was present in 57% of patients (ECOG 2: 12%, ECOG 3: 4%). At initiation of anti-PD1 treatment, 74% of patients presented with stage III/IV disease and 35% did not achieve a response to their latest prior therapy. The median duration of anti-PD1 treatment was 18.1 (0.5-79.3) months and 50% of patients still received an anti-PD1 antibody at data collection. One third (31.6%) of patients experienced grade III/IV treatment-related toxicities and a treatment delay of >6 weeks due to toxicity occurred in 15.5% of patients. Investigator-assessed ORR was 66.7% with 20.4% of patients achieving a CR and 46.3% a PR as best response (Figure 1A). With a median follow-up of 19.1 (0-74.7) months and 26.7 (0-74.7) for PFS and OS, respectively, median PFS (mPFS) and OS were 12.3 months and 32 months, respectively (Figure 1B+C). Corresponding 2-year PFS and OS estimates were 38.3% (95%CI 24.4-52.2) and 78.5% (95%CI 67.2-89.8). Median PFS was more favorable in patients achieving either a CR (30.1 months) or PR (24.9 months) compared to SD (9.3) or PD (3.4, Figure 1D), with similar trends also observed for OS. Two thirds (67%) of the 29 patients eventually experiencing PD, continued anti-PD1 treatment beyond progression at least once, with a median duration of 9.9 (3.0-25.8) until 2 nd PD. Overall, 28% patients received concomitant add-on treatments with radiotherapy (62.5%) and chemotherapy (25%) administered simultaneously most commonly. Best response to combination treatment was PR in 84.6% and SD in 15.4% of patients, and 75% of patients receiving add-on treatments achieved their best response only thereafter. Most common consecutive treatments were allogeneic stem-cell transplantation (N=5), BV-based therapy (N=5), Gemcitabine-based regimens (N=4) radiotherapy (N=4) and N=13 patients did not receive further treatment after anti-PD1 failure. Most common cause of death was cHL (58% of deaths reported), followed by non-anti-PD1 treatment-related causes (16%), infections and cardiac diseases (11% each) and second neoplasms (5%). Conclusions: In this multicenter cohort of older and frailer r/r cHL patients receiving anti-PD1 antibodies in routine care, safety and efficacy data including ORR, mPFS and mOS was similar to data reported from pivotal phase II trials. Anti-PD1 treatment for r/r cHL thereby appears feasible and able to induce meaningful clinical benefit in a broad range of patients. Despite various concomitant and subsequent treatments administered, however, cHL or subsequent treatments are by far the leading cause of death. Failure of anti-PD1 in r/r cHL hence constitutes an unmet need. Figure 1 Figure 1. Disclosures Trautmann-Grill: GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Kobbe: Celgene: Research Funding. Heinrich: Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Eisai: Consultancy; Lilly: Consultancy, Research Funding; Sanofi: Consultancy; Astra: Consultancy, Research Funding; Abbvie: Research Funding. Schmidt: Incyte: Honoraria; Biotest: Honoraria; Alexion: Honoraria; AbbVie: Honoraria; Sanofi-Aventis: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Hüttmann: Celgene: Honoraria; Gilead: Honoraria; Lead Discovery Center GmbH: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fuchs: Lukon: Honoraria; Celgene: Honoraria; MSD: Honoraria; BMS: Honoraria; Takeda: Consultancy, Honoraria. von Tresckow: Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Kite-Gilead: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Takeda: Consultancy, Honoraria, Other, Research Funding; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Pentixafarm: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; AstraZeneca: Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support. Borchmann: Gilead Sciences: Honoraria; BMS/Celgene: Honoraria; Janssen: Honoraria; Miltenyi Biotech: Honoraria; Novartis: Honoraria. Engert: MSD: Honoraria; Hexal: Honoraria; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy. Bröckelmann: BMS: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; MSD: Research Funding; BeiGene: Research Funding.

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Outcomes of Mismatched Related Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: A Retrospective Study on Behalf of the Chronic Malignancies Working Party of the EBMT

Blood ◽

10.1182/blood.v128.22.3504.3504 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3504-3504

Author(s):

Gwendolyn van Gorkom ◽

Michel van Gelder ◽

Dimitris Ziagkos ◽

Henric-Jan Blok ◽

Maria Teresa van Lint ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Gvhd Prophylaxis ◽

Related Donor ◽

Support Research

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a treatment for CLL that can give long disease control. Even with the availability of kinase and BCL2 inhibitors, HCT is still performed in fit patients (pts) with high-risk CLL. Almost exclusively, outcomes on matched related and unrelated donor transplantations in CLL have been published. Recently, mismatched related donors are gaining interest because of the better outcome of haploidentical HCT with post-transplantation cyclophosphamide (PTCY). Methods: All pts with CLL who received a first allogeneic HCT with a mismatched related donor and whose data were available in the EBMT registry were analyzed. Median values and ranges are reported for continuous variables and percentages for categorical variables. The probabilities of overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and the log-rank test for univariate comparisons. Relapse/progression and nonrelapse mortality (NRM) were analyzed together in a competing risk framework. Statistical analyses were performed using SPSS and R. Results: One-hundred-seventeen pts with CLL (74% males) underwent a mismatched related donor transplantation between 1984 and 2015 (1984-1999: 10, 2000-2004: 18, 2005-2009: 23, 2010-2016: 66). Median follow-up after HCT was 8 months (range 0-187 months). Median age at transplantation was 54 years (yrs) (range 27-71 yrs). Median time from diagnosis to HCT was 67 months (range 4-207 months). Eighteen pts (17%) had previously undergone autologous stem cell transplantation (ASCT). Disease status at HCT was CR in 16% of pts, PR in 39% and SD/PD in 45%. The Karnofsky score was known for 98 pts; 96% had a score of 70% or more at the time of HCT. Fifty-eight percent of pts received reduced-intensity conditioning, 42% myeloablative conditioning. Peripheral blood stem cells were used in 68% of pts, bone marrow in 32%. The HCT was sex matched in 41% of recipient-donor pairs. The relationship of the donor to the patient was known for 34 pts; in 53% the donor was a child, in 38% a sibling and in 6% a parent. Forty pts (38%) received PTCY as GVHD prophylaxis. In the other 77 pts various methods of T-cell depletion (TCD) were used, but not all methods were specified. At least 56% of those pts had in vivo TCD. For the whole cohort of pts OS at 2 and 5 yrs was 46% and 37%, respectively. PFS at 2 and 5 yrs was 38% and 30%, respectively. The use of PTCY did not have a significant impact on OS (49% vs. 42% at 2 yrs, 44% vs. 33% at 5 yrs, p=0.35) and PFS (45% vs. 31% at 2 yrs, 40% vs. 22% at 5 yrs, p=0.15). CI of NRM in the whole group at 2 and 5 yrs were 41% and 45%, respectively. CI of relapse at 2 and 5 yrs were 21% and 25%, respectively. The CI of NRM and relapse at 2 and 5 yrs were not statistically different in pts who received PTCY compared to other types of TCD (NRM: 38% vs. 45% at 2 yrs, 43% vs. 49% at 5 yrs, p=0.45; relapse: 17% vs. 25% at 2 yrs, 17% vs. 29% at 5 yrs, p=0.33). For the whole cohort, the incidence of acute graft-versus-host disease (aGVHD) at 100 days was 34% for grade II-IV and 16% for grade III-IV with a median time of onset of 23 days (range 4-57 days). Conclusions: Mismatched related donor HCT resulted in a 5-year PFS in 30% of the pts. This result seems only slightly inferior to matched donor transplant (5 yrs PFS 37%1). NRM was higher than expected in this cohort, but comparable to other studies on haploSCT with in vivo T-cell depleted grafts. In conclusion, a mismatched related donor HCT may be considered for high-risk chemoimmunotherapy-refractory or 17p deleted/TP53 mutated CLL pts without options for kinase and BCL2 inhibitor therapy. More data are needed to assess the value of PTCY for GVHD prophylaxis in this specific context. References: 1. Schetelig J, de Wreede L, Moreno C, et al. Risk factors for adverse outcome in patients with Chronic Lymphocytic Leukemia (CLL) undergoing Allogeneic Hematopoietic Cell transplantation (alloSCT): a Retrospective EBMT Analysis. Abstract WP024, EBMT meeting 2015. Figure 1 Figure 1. Disclosures Ciceri: MolMed SpA: Consultancy. Foà:Ariad: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Janssen-Cilag: Consultancy, Speakers Bureau; Genetech: Consultancy; Roche: Consultancy, Speakers Bureau. Hallek:Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau. Schetelig:Sanofi: Honoraria. Kröger:Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

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Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia: Why Do Adolescents and Young Adults Outcomes Differ from Those of Children? a Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Blood ◽

10.1182/blood-2021-146769 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2921-2921

Author(s):

Audrey Grain ◽

Fanny Rialland ◽

Patrice Chevallier ◽

Nicolas Blin ◽

Jean-Hugues Dalle ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Research Funding ◽

Cellular Therapy ◽

Lymphoblastic Leukemia ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Support Research

Abstract Introduction: Adolescents and Young Adults (AYA) represent a specific population in the Acute Lymphoblastic Leukemia (ALL) landscape, often presenting high-risk diseases and increased chemotherapy-related toxicities. Indications of Hematopoietic Stem Cell Transplantation for pediatric patients (HSCT) have been restricted to those with early poor response to chemotherapy. The same trend has led to a decrease of HSCT indications in AYAs, which are nevertheless still more frequent than in younger counterpart. Outcomes of AYAs after HSCT seemed to be worse than the ones of children in two previous studies published in 2013 and 2014. In Minneapolis, the decrease of overall survival in AYA was attributed to an excess of Treatment Related mortality (TRM) (28% versus 14%; p=0.04), but because of small numbers, factors influencing TRM were not identified. Our study aimed to compare, in a large cohort, the outcomes of children and AYA with ALL after HSCT and to determine factors influencing potential differences. Material and Methods: All patients aged between 1 and 25 years, reported in the SFGM-TC (Francophone Society of bone marrow transplantation and cellular therapy) registry, who received a first HSCT in treatment for ALL between 2005 and 2012 were included. The AYA group was defined by age range between 15 and 25 years old, according to European studies and the SFGM-TC. Data about diagnosis and transplantation procedure were prospectively collected in the registry. Before transplant procedure, patients or their parents/guardians provide a signed consent in order to be included in the registry. Results: 891 patients were included, 494 children and 397 AYA. Median time of follow up was 45.6 months (0 to 114). HSCT was performed in first CR for 56.8% of the AYAs, whereas 57.5% of children received HSCT in second CR or more advanced phase (p<0.001). HSCT procedures mainly included a Myelo-Ablative Conditioning (MAC) regimen. TBI was used more frequently in AYAs than in children (90.1% versus 83.1%, p=0.003). Bone Marrow (BM) or Cord-Blood (CB) were often used in children 60.2% and 29.4% versus 55.6% and 16.4% in AYA group respectively (p < 0.0001) . Peripheral Blood Stem Cells (PBSC) were more frequently used for AYA (28%) than for children 10.3% (p < 0.0001). Moreover, when being transplanted in an adult center, PBSC were more commonly used for AYA (30% of AYA's HSCT in adult centers versus 21.2% of AYA's HSCT in pediatric centers, p=0.051). BM and PBSC cells were provided by a match sibling donor (MSD) in 40.2% of children and 43.4% of AYAs and from a MUD in 57.2% and 55.1% of cases respectively (p = 0.474). Anti-thymoglobulins (ATG) were used for 336 patients (48% of children and 26% of AYA patients, p<0.001). See patient's characteristics in Table. Five-year OS was lower in AYA 53.1% versus 64% (p = 0.0012) and we confirmed higher 5-years TRM in AYA 19% versus 13% (p=0.04). TRM incidence markedly rose after 10 years of age (from 9% before 10 years old to 20% between 10 and 15 years, and 17% after 15 years). Graft versus host disease and Relapse Free Survival probability (GRFS) was lower in AYA: 36% versus 47% (p=0.007), while Cumulative Incidence of Relapse (CIR) and acute Graft versus Host Disease (GvHD) incidence were both similar in our two groups: 32% and 61% in AYAs versus 27% and 59% in children, (p=0.19 and p=0.62), respectively. Thus, chronic GvHD, which occurred more frequently in AYA than in children (32% versus 19%, p<0.001), mainly impact post-HSCT morbi-mortality in AYA (Figure 1 and 2). In our multivariate analysis, two factors were associated with higher risk of cGvHD: use of PBSC as stem cell source (HR 1.41 [0.96-2.07], p=0.083), and absence of ATG use (HR associated with use of ATG: 0.62 [0.42-0.92], p=0.017) (Figure 3). Of note a subgroup analysis in patients who received a bone marrow transplant after a MAC, showed no TRM difference between AYA and children. Conclusion: AYA or patients aged more than 10 years, compared to ones aged less than 10 years have a worse outcome after HSCT for ALL. Excess of death in this specific population is mainly due cGvHD. Transplantation practices in those patients, particularly choice of stem cells source and GvHD prophylaxis, should be discussed. Their treatment adherence should also be questioned and reinforced by development of multidisciplinary teams. Figure 1 Figure 1. Disclosures Peffault De Latour: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Jazz Pharmaceuticals: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Forcade: Novartis: Other: travel grant.

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Conditioning with Treosulfan and Fludarabine for Patients with Refractory or Relapsed Non-Hodgkin Lymphoma (NHL),

Blood ◽

10.1182/blood.v118.21.4106.4106 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4106-4106

Author(s):

Michael Schmitt ◽

Rudolf Trenschel ◽

Herbert G. Sayer ◽

Catarina Schneider ◽

Aenne Glass ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Hodgkin Lymphoma ◽

Cell Transplantation ◽

Research Funding ◽

Positive Impact ◽

Disease Free Survival ◽

Hematopoietic Stem ◽

Non Hodgkin Lymphoma ◽

Travel Grant

Abstract Abstract 4106 Background: Treatment of refractory or relapsed non-Hodgkin lymphoma (NHL) remains challenging. Here, 88 patients with refractory or relapsed NHL received treosulfan and fludarabine as a reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Material and Methods: 73/88 intensely pre-treated patients experienced a relapse (R) with 18/88 early relapses (ER < 6 months from the last chemotherapy). At the time of allo-HSCT, 26 patients were in complete (CR) and 43 in partial remission (PR), twelve patients had progressive disease (PD) and seven stable disease (SD). 47 patients received an autologous graft followed by allo-HSCT. Results: After allo-HSCT, 69 of 88 patients were in CR, seven patients in PR, resulting in an overall response rate of 86.4% (76/88). Thirty-three patients achieved a CR from PR as well as six patients from PD and five from SD. 43/88 (49 %) patients were alive at the end of follow-up. Patients undergoing directly allo-HSCT without preceding auto-HSCT showed a better disease-free survival (DFS, p =.038) with a trend (p =.077) for better overall survival (OS). Patients with ER showed an OS of.35 ±.12 after three and seven years. Chronic graft-versus-host disease (cGvHD) had a positive impact on both OS and DFS (for limited cGVHD versus no cGvHD p =.002 and.004, respectively). Conclusion: Allogeneic stem cell transplantation following conditioning with treosulfan and fludarabine constitutes a good therapeutical option for patients with refractory or relapsed NHL and should be considered early in the course of salvage treatment. Disclosures: Schmitt: Medac: Participation in Conferences. Sayer:Medac: Travel grant to ASH 2009. Koenigsmann:Medac: Research Funding. Casper:Medac: Participation in Conferences. Beelen:Medac: Participation in Conferences. Freund:Medac: Honoraria, Research Funding.

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Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Blood ◽

10.1182/blood-2019-127238 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4574-4574

Author(s):

Anna Waszczuk-Gajda ◽

Junfeng Wang ◽

Liesbeth C. de Wreede ◽

Tiarlan Sirait ◽

Zubeyde Nur Ozkurt ◽

...

Keyword(s):

Quality Of Life ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Research Funding ◽

Advisory Committees ◽

Safety And Efficacy

Introduction Multiple myeloma (MM) patients with renal impairment (RI), especially dialysis-dependent (DD) RI, have poorer outcomes than MM patients with normal renal function. Autologous stem cell transplantation (ASCT) is a treatment option, but there is concern at a perceived higher risk of complications which may be limiting consideration of the use of ASCT in this population. The evidence is inconsistent among studies and interpretation is complicated by heterogeneous datasets, some dating to before the availability of novel agents. Finally, the reversibility of RI following ASCT is an important prognostic factor for both survival and quality of life. Aim To evaluate the safety and efficacy of ASCT in MM patients with DD RI transplanted in EBMT centres between 1997 and 2017. Methods Baseline characteristics at diagnosis, patient treatment regimens and clinical outcomes were collected using standardised report forms. OS was defined as the period between the date of ASCT and the date of death or the date of last observation. PFS was defined as the period between the date of ASCT and date of progression/relapse or death of any causes or the date of the last observation. Cox proportional hazard regression analysis was applied to assess risk factors for progression and death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank test. P<0.05 was judged as statistically significant. Results A total of 109,959 adult MM patients are registered in the EBMT database as having undergone ASCT between 1997 and 2017. We further analysed 118 DD MM patients who had a first ASCT during this period. The median (range) age was 57 (27-71) years. Seventy (59%) patients were males. Forty nine patients (49/94 patients, 52%) had Karnofsky score ≥90. One hundred and ten patients were treated with hemodialysis and eight with peritoneal dialysis. A total of 68 (58%) patients had Light Chain MM, 43 kappa and 25 Lambda. In first-line induction therapy, 47/76 (62%) patients received bortezomib-based regimens. Forty-four (37%) patients achieved at least VGPR pre-ASCT. The median time from diagnosis to ASCT was 0.7 years (0.3-4.9). Melphalan doses were as follows: 140 mg/m2 (n=55, 67%), 70-100 mg/m2 (n=15, 18%), and >140 mg/m2 (n=12, 15%). The times to Neutrophil (>0.5) and Platelet (>20) engraftment were 12 (10-37) and 14 (4-128) days, respectively. The 30-day and 100-day transplant-related mortality (TRM) rates were 0.0% and 0.9%, respectively. ASCT was associated with a significant deepening of response (at least VGPR pre- vs post-ASCT: 36/93 (39%) vs 48/93 (52%), p < 0.001). The median PFS was 37 months (95% CI: 24-43) and 5-year PFS was 31% (95% CI: 20-41). The median OS was 102 months (95% CI: 67-129). Five-year OS post-ASCT was 62% (52-72) and 10-year OS 36% (17-55). Thirty-one (26%) DD MM patients achieved dialysis independence. There were no differences in PFS or OS when comparing the 1997-2007 and 2008-2017 cohorts: 5-year PFS - 28% (6-49) vs 31% (19-43) (p=0.7) and 5-year OS - 61% (38-84) vs 63% (51-74) (p=0.9), respectively. On univariate analysis of factors affecting PFS, achievement of an Overall Response Rate (ORR) (CR+VGPR+PR vs. Other) pre-ASCT was associated with a lower risk (HR 0.467, p=0.032) and older age (>55 years) with a higher risk (HR 1.786, p=0.035) of post-ASCT progression. Age higher than 55 (HR 2.033, 95%CI: 0.992 - 4.166, p=0.053) increased and achievement of at least VGPR pre-transplant (HR 0.494, 95%CI: 0.224 - 1.091, p=0.081, on the verge of statistical significance) decreased the risk of death. Conclusion To the best of our knowledge, the DIADEM study is the largest analysis of ASCT in DD MM pts to date. This cohort of 118 unselected patients had an OS comparable to patients without RI. This may reflect patient selection based on younger age, Karnofsky scores and pre-ASCT response. The low TRM and excellent outcomes support consideration of the use of ASCT in pts with DD RI. Notably, more than a quarter of patients became dialysis independent, an outcome likely to confer an improved Quality-of-Life.. These results can also inform the debate around the role of renal transplantation in younger DD MM patients who do not achieve dialysis independence. Disclosures Snowden: IDMC: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Mallinckrodt: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Dreger:MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; Neovii, Riemser: Research Funding. Illés:Takeda, Seattle: Research Funding; Janssen, Celgene, Novartis, Takeda, Roche, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Basak:Teva: Honoraria; Celgene: Honoraria. Gyan:Pfizer: Honoraria. Hayden:Alnylam: Honoraria; Amgen: Honoraria. Beksac:Amgen: Consultancy; Celgene: Consultancy; Janssen&Janssen: Consultancy; Takeda: Consultancy. Schönland:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Long-Term Survival after Autologous Stem Cell Transplantation in a Colombian Population

Blood ◽

10.1182/blood-2018-99-119715 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4626-4626

Author(s):

Claudia Lucia Sossa ◽

Luis Antonio Salazar ◽

Angela María Peña ◽

Edgar Gomez ◽

Claudia Marcela Chalela ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Hodgkin Lymphoma ◽

Cell Transplantation ◽

Cause Of Death ◽

Disease Stage ◽

Post Transplantation ◽

Common Cause ◽

One Year

Abstract Introduction: Autologous hematopoietic stem cell transplantation (auto-HSCT) is a complex medical process that has evolved throughout the years, becoming a potentially curative therapy for many hematologic neoplasms and non-malignant marrow disorders, as well as a clinical option for some autoimmune diseases. During the past decades, HSCT has had important advances in technology and technique, patient supportive care, and conditioning protocols, making it a safer procedure. As a result, patient survival rates continue improving. Nonetheless, it is unclear if these improvements are also seen in developing countries. The aim of the present study is to assess survival rate for patients who underwent auto-HSCT in a Colombian population. Methods: A retrospective cohort study was conducted at a tertiary referral center in Colombia, South America, on patients who underwent auto-HSCT between November 2009 and December 2017. Descriptive statistics were used to analyze patient's demographic characteristics. The Kaplan-Meier method was used to assess overall survival (OS) and relapse-free survival (RFS) rates at 100 days, one year, and five years following auto-HSCT. Results: One hundred and fifty-seven patients were included, with a mean age of 49.54 years (range 14-71). Seventy-nine (50.31%) were men. Classifying patients by age group, 68.7% of the patients (n=108) were in the 20-60 years old group and 28% (n=44) were older than 60 years. The most common indication for auto-HSCT was multiple myeloma (42.7%), followed by non-Hodgkin lymphoma (35%) and Hodgkin lymphoma (13%). Peripheral blood stem cells were the graft source in all patients (100%). High-dose melphalan (MEL 200) was the conditioning regimen administered to patients with diagnosis of multiple myeloma, and BEAM (carmustine, etoposide, cytarabine, and melphalan) to patients with lymphoma. OS was 91.7% (CI95% 86.2-95.1) at 100 days, 81% (CI95% 73.9-86.4) at one year, and 60.9% (CI95% 51.3-69.1) at five years. RFS was 94.9% (CI95% 90-97.4) at 100 days, 86.3% (CI95% 79.7-90.8) at one year, and 70.5% (CI95% 66.6-80.7) at five years. Classifying patients by pre-transplantation disease stage as defined by the EBMT study group, OS for early disease was 85.5% (CI95% 75.6-91.8) at one year and 58.2% (CI95% 43.7-70.2) at 5 years, 88.1% (CI95% 76.5-94.1) at one year and 51.8% (CI95% 33.9-66.9) at 5 years for intermediate stage, and 100% at one year and 42.3% (CI95% 7.3-75.4) at 5 years for advanced disease. The most common cause of death was disease progression. There were 51 deaths (32.48%) post-transplantation, 5.73% (n=9) in the first 100 days, 7.6% (n=12) between 100 days and 1-year, and 18% (n=29) after the first-year post-transplantation. Non-relapse mortality was 3.2% at both 100 days and 5 years. Conclusion: OS and RFS of auto-HSCT were very similar to the outcomes reported in the existing literature mainly assessed in developed countries. The most common cause of death in patients who underwent auto-HSCT was progression of the primary disease, and transplant-related mortality was low. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Is the End Close for the Graft-Versus-Host Disease That Is a Big Problem Following Allogeneic Hematopoetic Stem Cell Transplantation?

Blood ◽

10.1182/blood-2018-99-112339 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5729-5729

Author(s):

Osman Ilhan ◽

Guldane Cengiz Seval ◽

Zubeyde Nur Ozkurt ◽

Ali Ugur Ural ◽

Meltem Ayli ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Graft Versus Host Disease ◽

Research Funding ◽

Chronic Gvhd ◽

Graft Versus Host ◽

Hematopoetic Stem Cell ◽

Hematopoetic Stem Cell Transplantation ◽

Support Research ◽

Steroid Refractory

Abstract Introduction:Despite major improvements in allogeneic hematopoetic stem cell transplantation (Allo-SCT) form matched related/unrelated donor over last decades, chronic graft-versus-host disease (cGVHD) is still the leading cause of late treatment-related deaths among recipients (Lee et all, Blood2002). Novel insights into the pathophysiology of GVHD highlighted the relevant role of the host inflammatory response governed by Bruton tyrosine kinase (BTK) signaling pathway. Ibrutinib is a first class, once daily inhibitor of BTK with proven efficacy in B cell lympho-proliferative diseases, was recently employed in corticosteroid- refractory chronic GVHD with encouraging overall response rates(Miklos et all, Blood 2017). Patients and Methods:This real-life, multicenter retrospective study conducted in 6 centers from Turkey included 14 adult patients diagnosed with steroid-refractory cGVHD. All patients were transplanted using grafts from HLA-matched peripheral blood stem cell source. We treated off-label these patients from June 2017 to July 2018 with ibrutinib with a dose of 420 mg P.O. qday. Organ sites affected and cGVHD grading before starting ibrutinib were classified according to the National Institues of Health (NIH) 2014 criteria. Steroid refractory cGVHD was defined as any disease that failed to respond to previous immunosuppressive therapy with steroids at least 4 weeks or inability to taper it with or without additional immunosuppressive drugs. Results:The baseline characteristics of the patients are listed in Table 1. Patients had undergone both myeloablative and non-myeloablative Allo-SCT for a variety of underlying hematological malignancies. As expected mouth and skin were the most frequently involved organs and 79% of patients showed evidence of cGVHD in more than 2 organs. The median Karnofsky Performance Status score was 75% (30%-100%). At a median follow-up of 26.7 months (range, 3.2-70.9 months) after evidence of cGVHD showed, 12 (85.7%) patients were still receiving ibrutinib and 2 (14.3%) had discontinued treatment, because of cGVHD progression. Treatment duration ranged from 2 to 12 months (median 6 months) for all patients. Only one patient had grade 2 muscle spasms as adverse event and need to reduce the 25% of drug dosage. No several adverse events due to ibrutinib was observed in our cohort. In the all treated population, the overall response rate (ORR), based on the 2005 NIH cGVHD Consensus Panel response criteria, was 71.4%, with a CR rate of 28.6 % and a PR rate of 42.9 %. For the responders, the median time to initial response was 28 days. Two patients had stable disease under the ibrutinib treatment and still continue receiving. Analysis by organ domain showed similar rates of response in the skin (91.7%), lung (85.7%) and mouth (80%). However the response in the liver (71.4%) was lower than the others. At the time of data collection, no patient has deceased. Discussion:In the absence of an approval treatment of steroid-refractory cGVHD, there is currently no consensus on the optimal second-line treatment. Treatment choices are based on mostly physician experience, ease of use and risk of toxicity. Based on the results of our limited study; the clinically meaningful response with safety profile observed with ibrutinib as a salvage therapy for chronic GVHD in accordance with Miklos and colleagues's report. However, in contrast to their results; patients with skin and lung manifestations of cGVHD were appeared to have somewhat better responses to ibrutinib than patients with cGVHD involving liver. It is important to note that prospective randomized controlled studies with large number of patients are warranted to find out the standard regimen for steroid-refractory cGVHD. Disclosures Ilhan: Alexion: Speakers Bureau; Roche: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau. Civriz Bozdag:TAKEDA: Consultancy; MSD: Research Funding; NOVARTIS: Consultancy. Özcan:Takeda: Honoraria, Other: Travel payment, Research Funding; Novartis: Research Funding; Roche: Honoraria, Research Funding; Abbvie: Other: Travel payment; Jazz: Other; Janssen: Other: Travel Support, Research Funding; BMS: Honoraria; Bayer: Research Funding; MSD: Research Funding; Celgene: Other: Travel support, Research Funding; Archigen: Research Funding; MSD: Other: travel support, Research Funding; Jazz: Other: Travel support.

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Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood.v126.23.520.520 ◽

2015 ◽

Vol 126 (23) ◽

pp. 520-520 ◽

Cited By ~ 1

Author(s):

Gunjan L Shah ◽

Kurt S Bantilan ◽

Stephanie L Verwys ◽

Susan J McCall ◽

Joachim Yahalom ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Hodgkin Lymphoma ◽

Salvage Therapy ◽

Research Funding ◽

Stage Iv ◽

Salvage Chemotherapy ◽

Stage Iv Disease

Abstract Introduction: Limited information exists on the best treatment strategy for Primary Refractory (ref) Hodgkin Lymphoma (HL). For the past 20 years, we have treated patients (pts) on sequential ifosfamide, carboplatin, etoposide (ICE)-based clinical trials with the intent to undergo high dose therapy (HDT) and autologous stem cell transplantation (ASCT). As previously reported (Moskowitz, Blood 2010) and confirmed by other centers, a negative PET scan prior to ASCT predicts for marked improvement in outcome in pts with relapsed HL. We aimed to identify risk factors that predict PET response to salvage chemotherapy in ref HL and evaluate outcomes following HDT and ASCT in this patient population. Methods: From 10/1/94 to 7/10/15, 192 ref HL pts were treated on sequential trials at MSKCC. Demographic and clinical factors were collected. Event free survival (EFS) and overall survival (OS) were calculated from the date of histologic confirmation of ref disease, estimated by Kaplan-Meier method, and compared by the log rank test. Events included relapse or death. Cox regression was used for the multivariate regression model. Patients were selected to receive a radiation-based conditioning regimen if all sites of nodal disease could be encompassed into a radiation field. Results: Patient characteristics included a median age of 31 (range 14-79) with 54% female. B symptoms, extranodal disease, stage IV disease, and disease bulk > 5cm were present in 31%, 48%, 44%, 40%, respectively. In the intent-to-treat (ITT) population, 41% had a positive post-salvage PET scan. As analyzed by ITT, median EFS was 8.9 years with a median OS of 10.4 years. On multivariate analysis, the presence of B symptoms and bulk >5cm at documentation of ref disease predicted for a reduced chance of achieving a negative PET after salvage therapy, with an odds ratio (OR) of 2.03 for B symptoms and 2.13 for bulk >5cm. For the 169 (88%) transplanted patients, 68% had a negative pre-ASCT PET. Radiation based conditioning was used for 70% of the pts. Median EFS was 12.8 yrs and median OS was not reached with a median follow-up of 3.6 yrs (range, 0.55 to 18.04 yrs) for the surviving patients (Figure 1). On multivariate analysis, both stage (IV vs I-III) and persistent PET abnormality pre- ASCT correlated with a shorter EFS. A risk stratification model was created and pts could be divided into 4 groups. 1) stage I-III disease and a negative PET pre-ASCT, the median EFS was not reached; 2) stage I-III disease and a positive PET pre-ASCT scan-the OR of an event was 4.04 (95% CI 1.93 to 8.45) with the median EFS not reached, 3) Stage IV disease and a negative PET pre-ASCT, the OR was 3.78 (95% CI 1.64 - 8.74) with a median EFS of 8.9 yrs, 4) Stage IV disease and a positive PET pre-ASCT, the OR was 8.22 (95% CI 3.99 to 16.94) with a median EFS of 0.9 yrs (Figure 2). Conclusions: B symptoms and bulk >5cm predicted for residual PET avidity after salvage therapy in ref HL. Persistent PET abnormality pre-ASCT and stage were risk factors for earlier relapse and death and can be used to prognosticate survival. Further studies are needed to determine optimal therapy for patients with multiple risk factors. Figure 1. EFS for the Transplanted Patients Figure 1. EFS for the Transplanted Patients Figure 2. EFS for the transplanted pts based on the presence of risk factors (PET avidity pre-HSCT and Stage) Figure 2. EFS for the transplanted pts based on the presence of risk factors (PET avidity pre-HSCT and Stage) Disclosures Moskowitz: GSK: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.

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PD-1 Blockade with Pembrolizumab for Classical Hodgkin Lymphoma after Autologous Stem Cell Transplantation

Blood ◽

10.1182/blood-2018-99-113685 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1650-1650 ◽

Cited By ~ 2

Author(s):

Philippe Armand ◽

Yi-Bin Chen ◽

Robert A. Redd ◽

Robin M. Joyce ◽

Jad Bsat ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Board Of Directors ◽

Hodgkin Lymphoma ◽

Autologous Stem Cell Transplantation ◽

Research Funding ◽

Classical Hodgkin Lymphoma ◽

Advisory Committees

Abstract Background: Classical Hodgkin lymphoma (cHL) displays near-universal genetic deregulation of PD-1 ligand expression, and relapsed/refractory (R/R) cHL is uniquely sensitive to PD-1 blockade. However, such treatment for patients (pts) who relapse after or are ineligible for autologous stem cell transplantation (ASCT) appears to be rarely, if ever, curative. Deploying PD-1 blockade early after ASCT could leverage the remodeling immune landscape and minimal residual disease state to increase the cure rate of ASCT. We therefore conducted a phase 2 multi-center single-arm study of the anti-PD-1 monoclonal antibody pembrolizumab (pembro) in pts with chemosensitive R/R cHL after ASCT. Another arm of this study enrolled pts with R/R DLBCL and will be presented separately. Methods: Adult pts with R/R cHL who had received 2-3 lines of prior therapy and ASCT and who were chemosensitive prior to ASCT were enrolled on this study. In addition to meeting standard eligibility criteria for pembro treatment, pts had to have recovered from ASCT toxicities and begin study treatment within 60 days of stem cell infusion (goal within 21 days). They received pembro 200mg IV every 3 weeks for 8 cycles. PET-CT scans were obtained at post-ASCT baseline, after 3 and 7 cycles, then at 12 and 18 months post-ASCT. The primary endpoint was the progression-free survival rate (PFS) at 18 months after ASCT, assessed using International Harmonization Project 2007 criteria. Results: 31 pts were enrolled and 1 withdrew consent before starting treatment. Among the 30 eligible patients, median age was 33 (20-69). 26 pts (87%) were high-risk by virtue of primary refractory disease (57%), relapse within 12 months (17%), extranodal disease at relapse (27%) or absence of metabolic CR at ASCT (10%). At study baseline post-ASCT, 97% were in CR. 24 pts (80%) completed 8 cycles of pembro per protocol. 6 pts (20%) stopped pembro early for pt choice (n=2, including 1 pt with gr2 pneumonitis) or toxicity (n=4, including 2 pts with gr3 hepatitis, 1 with g3 pneumonitis, 1 with g2 diplopia). 9 pts (30%) experienced a total of 28 gr3 or higher adverse events (AEs). The most common gr4 AE was neutropenia (10%). 3 patients (10%) experienced 7 gr3-4 AEs at least probably related to pembro (gr3 diarrhea and gr3 eosinophilic colitis in 1 pt, gr3 leukopenia and gr4 neutropenia in 1 pt, gr3 leukopenia and gr3 ALT and AST elevation in 1 pt). 11 pts (37%) experienced at least one immune-related AE of gr2 or higher severity: pneumonitis (n=2 gr2, n=1 gr3), thyroid dysfunction (n=1 gr2), transaminitis (n=2 gr3), colitis/diarrhea (n=1 gr2, n=2 gr3), rash (n=2 gr2), pulmonary hemorrhage (n=1 gr3), arthritis (n=1 gr2), and increased creatinine (n=1 gr2). There was no treatment-related death. Among the 30 eligible pts, 2 were lost to follow-up after their 12m assessments (both in CR). 27 pts (90%) were evaluable for the primary endpoint (the last pt is still in follow-up and results will be updated for the meeting). 6 patients (20%) relapsed at a median of 8 months (3-18) from ASCT, and all other evaluable patients were in CR at the 18m timepoint. The KM estimate of 18m PFS for high-risk patients was 78% (95%CI 54-91). The 18m overall survival was 100%. Tumor biopsies from a pt who progressed on study demonstrated an increase in the %age of PD1+ T cells at progression, as well as an increase in the %age of PD-L1+ macrophages and PD-L1+ Reed-Sternberg cells (Figure). Other correlative studies including immune reconstitution and MRD analyses are ongoing. Conclusions: Pembrolizumab administered after ASCT in patients with R/R cHL has a safety profile that appears similar to its use in the R/R setting, although possibly with a higher rate of neutropenia. The 18-month progression-free rate in this high-risk cohort compares favorably with previous published studies, and supports the hypothesis that PD-1 blockade in this setting may increase the efficacy of ASCT. This should be tested in a randomized trial. Figure. Figure. Disclosures Armand: Pfizer: Consultancy; Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy; Adaptive: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Chen:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Consultancy; Magenta Therapeutics: Consultancy; REGiMMUNE: Consultancy. LaCasce:Humanigen: Consultancy, Honoraria; Research to Practice: Speakers Bureau; Bristol-Myers Squibb: Other: Data safety and monitoring board; Seattle Genetics: Consultancy, Honoraria. Jacobson:Pfizer: Consultancy; Humanigen: Consultancy; Precision Bioscience: Consultancy; Novartis: Consultancy; Kite: Consultancy; Bayer: Consultancy. Jacobsen:Merck: Consultancy; Seattle Genetics: Consultancy. Rodig:Bristol-Meyers-Squibb: Research Funding; KITE Pharma: Research Funding; Affimed Inc.: Research Funding; Merck & Co., Inc.: Research Funding. Shipp:AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Merck: Research Funding. Herrera:BMS: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; KiTE Pharma: Consultancy, Research Funding; Seattle Genetics: Research Funding; Immune Design: Research Funding; Astra Zeneca: Research Funding.

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RIC Allogeneic Stem Cell Transplantation for High Risk CLL Followed By Preemptive MRD-Based Immunointervention - Intermediate Results from the Phase II ICLL03 Ricac-Pmm Trial (FILO & SFGM-TC French intergroup)

Blood ◽

10.1182/blood.v126.23.3222.3222 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3222-3222

Author(s):

Olivier Tournilhac ◽

Magali Le Garff-Tavernier ◽

Reza Tabrizi ◽

Stephanie Nguyen quoc ◽

Faize Legrand-Izadifar ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Graft Rejection ◽

Research Funding ◽

Limit Of Detection ◽

Color Flow ◽

Support Research

Abstract Introduction Reduced intensity conditioning (RIC) allogeneic stem cell transplantation (ASCT) remains a valuable and potentially curative strategy in high-risk CLL. Post-ASCT relapse remains an important (30-40%) cause of failure, predicted by persisting positive minimal residual disease (MRD) at 12m post-ASCT. ASCT is also associated with a toxic mortality and with the burden of chronic graft versus host disease (cGVHD). We evaluated the efficacy and safety of a preemptive immunointervention (PrIm) based on serial MRD assessment in high-risk CLL. (NCT01849939) Methods Main inclusion criteria were (1) EBMT criteria for ASCT, (2) CLL in PR/CR, (3) mass ≤5cm, (4) age ≤70, (5) SORROR score ≤2 and (6) HLA donor (10/10). RIC regimen included fludarabine 120 mg/m2, IV busulfan 6.4 mg/kg, rabbit ATG 5mg/kg and CsA prophylaxy. Centralized 10-color flow cytometry blood MRD was assessed before and at M1, M2, M3, M4, M5, M6, M9 and M12 post-ASCT. MRD[-] was defined by blood detection <10e-4 at 2 consecutive time-points, confirmed (if possible) on bone marrow aspiration. PrIm algorithm, applied from D30 to M12, considered IWCCL response criteria, blood MRD and GVHD occurrence/severity. PrIm comprised tutored CsA early (≤4-5m), standard (6m) or late (7m) tapering and discontinuation (T&D). Early CsA T&D was followed in case of failure to achieve MRD[-] by 1-3 increasing DLI doses (1, 5 or 10x10e6 CD3/kg). Primary end point was the rate of MRD[-] at M12. Chimerism was assessed in parallel on full blood and on sorted CD3+ cells and was not a part of PrIm decision. Results As of 2015, August the 1st, the 43 planned inclusions have been done. Before their last line prior to ASCT, pts had: (a) presence of a del(17p) in 1st line (n=24) or in relapse (n=3), (b) absence of del(17p) but relapse ≤2y post fludarabine-based combination (n=14) or post-autologous transplantation (n=1). At time of transplantation, 11/43 (26%) had achieved CR, 28/43 (65%) had achieved PR, 2/43 (5%) had SD with 2 unknown status. Six patients had undetectable MRD (limit of detection: 5x10-6). For the 37 other patients, the median pre-ASCT MRD level was 2.35%(0.014 to 70%). The results of these 43 pts will be available in December 2015. This abstract describes the outcome of the 30 first consecutive pts including 26 pts evaluable [alive with ≥12m post-ASCT follow-up] and 4 pts non evaluable [death at M10 (n=1; sepsis) and at M8 (n=1 GVHD), EBV induced lymphoproliferation (n=1) and immediate graft rejection (n=1)], all included in the ITT analysis. In the 29 pts with full engraftment, the full blood chimerism at 3m and 12m was 99.1[62.1 ;99.8] and 99.5[59.4 ;99.9], and the T-cell specific chimerism was 99.2[5.2;99.8] and 99.6[21.1;99.8], with 30% and 25% >95% donor derived CD3+ cells respectively. MRD evolution followed different patterns (Table 1). At the M3 checkpoint, among evaluable patients, 10 were already MRD[-], and 16 were still MRD[+]. Then 10 pts became MRD[-] and 6 remained MRD[+]. This approach achieved 67% blood MRD[-] at M12 (ITT). When early CSA T&D had failed DLI done in 6 pts did not achieve MRD negativity. Finally, 6 pts (20%) remained MRD[+] at 12m. At 12m FU, the rate of Gr≥2 aGVHD was (11/30) 37% (consecutive to early CsA T&D in 2 pts and to early CsA T&D followed by DLI in 1 pt) and the rate of extensive cGVHD was (5/29) 17% (consecutive to CsA T&D in 1 pt). Hence we observed the occurrence of Gr≥2 aGVHD and extensive cGVHD in 2/8 and 1/8 pts after early CsA T&D. We also observed one case of Gr≥2 aGVHD among the 6 pts who had early CsA T&D followed by DLI. Eighteen severe adverse events were reported, including the 2 aforementioned deaths. These events were not related to the study procedure (PrIm). Discussion These preliminary data highlight the feasibility, safety and efficacy of a standardized PrIm strategy in high-risk CLL. As DLI appears to have limited impact when CsA T&D fails, the preemptive use of new agents should be considered at this point for persistent MRD[+] after 3-6m post-ASCT. Table 1. Table 1 M12 MRD N % MRD[-] pre-ASCT remaining MRD[-] [-] 2 7 MRD[+] (M1-2) spontaneously translating to MRD[-] within 3m [-] 8 27 MRD[+] (M1-3) translating to MRD[-] after early CsA T&Dconcomitant of severe GVHD (≥G2 aGVHD and/or ext cGVHD) [-] 10 8 2 33 MRD[+] (M1-3) remaining MRD[+] despite early CsA T&D followed by DLIdespite early CsA T&D, transient MRD[-], relapse and DLI [+] 6 5 1 20 Non evaluable: toxic deaths (2), EBV LPD (1), graft rejection (1) NE 4 13 Disclosures Tournilhac: GSK: Other: Travel Support, Research Funding; Mundiphrama: Honoraria, Other: Travel Support, Research Funding; Celgene: Other: Travel support; Roche: Other: Travel support, Research Funding; Janssen Cilag: Honoraria, Other: Travel support; Gilead: Other: Travel Funding.

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