Search

Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.\ud \ud Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life.\ud \ud Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P

Salvage chemotherapy and autologous stem cell transplantation (auto-SCT) results in the cure of around 50% of patients with Hodgkin lymphoma (HL) failing first line therapy. In historical data, patients who progressed after auto-SCT had a poor outcome, with a median overall survival (OS) of around 1-2 years. Significant progress has been achieved in the last decade with the use of brentuximab vedotin (BV) or check-point inhibitors (CPI) and the increasing use of haploidentical transplant. However, little information is available about the characteristics and real-world outcomes of patients with HL relapsing after auto-SCT in the current era. To assess prognosis of patients with recurrent-HL post auto-SCT over time, we analyzed the European Blood and Marrow Transplant registry data of 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. A specific questionnaire was sent to all participant centers to obtain additional data regarding characteristics of the patients, treatment of relapse and outcome after auto-SCT failure. Detailed data were collected for 760 patients [median age 32; interquartile range (IQR) 25-42] included in this study. After a median follow-up for alive patients of 57 months (IQR: 29-89), the 4-year OS after relapse for the 760 included patients was 46% (95%CI: 43-50) and similar to that of 1021 non-included patients (45%, 95%CI: 41-48). The 4-year OS after relapse continuously increased from 35% (95%CI: 27-45) for 136 patients relapsing in 2006-2008, to 43% (95%CI: 37-49) for 258 patients relapsing in 2009-2011, 49% (95%CI: 43-56) for 238 patients relapsing in 2012-2014, and 61% (95%CI: 52-72) for 128 patients relapsing in 2015-2017 (p=0.001) (Figure 1). Improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p=0.01) but not in those with a late relapse (p=0.6). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status at relapse, bulky disease at relapse, extranodal disease at relapse and presence of B-symptoms at relapse were associated with a worse OS. Regarding treatment at relapse, BV was used in 233 patients (31%) after a median of 2 months from relapse (IQR: 0.8-8), predominantly as first treatment of relapse (155 patients). BV use increased over the 4 time periods from 3% to 19%, 49% and 49% respectively, and resulted in a complete remission (CR) in 46% and a partial response (PR) in 32%. The 4-year OS from BV use for relapse after auto-SCT was 56% (95%CI: 49-64). CPI were used in 91 patients (12%) including nivolumab in 75 patients and pembrolizumab in 12 patients after a median of 18 months from relapse (IQR: 5-35). CPI use increased over the 4 time periods from 1% to 4%, 14% and 35% respectively, and resulted in a CR of 44%, PR 32%, with a 4-year OS from CPI use of 44% (95%CI: 30-63). Finally, a second SCT (SCT2) was performed in 330 patients (43%) predominantly allogeneic SCT (285 patients, 86%) including a haploidentical SCT in 54 patients (16%). SCT2 was performed in 40% and 37% of patients relapsing in 2006-2008 and 2009-2011 respectively but its use increased to 49% and 51% of patients relapsing in 2012-2014 and 2015-2017 respectively. Four-year OS after SCT2 was 55%. In conclusion, outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse, possibly reflecting, among other factors, the efficacy of post-transplant salvage including BV, CPI and second transplant. These large-scale real-world data can serve as benchmark for future studies in that setting. Figure 1 Disclosures Blaise: Jazz Pharmaceuticals: Honoraria. Sureda Balari:Incyte: Consultancy; Celgene: Consultancy, Honoraria; BMS: Speakers Bureau; Roche: Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.

Patients with relapsed or refractory (R/R) Hodgkin Lymphoma (HL) after first autologous stem cell transplantation (ASCT1) may be offered several therapeutic options. New agents such as brentuximab vedotin or checkpoint inhibitors have recently been approved for the treatment of these patients, however, their efficacy to provide long-term control or cure is still unknown. Thus, a significant proportion of patients are still considered candidates for a second hematopoietic stem cell transplantation, usually an allogeneic transplantation. A second ASCT (ASCT2) has historically been considered as an option only in a small group of patients so the published experience is scarce. We retrospectively evaluated the outcome of 56 adult patients (25% female/75% male) with R/R HL registered in the EBMT database who received an ASCT2 between 2005 and 2014. Planned tandem ASCT were excluded. The median age at ASCT2 was 33 years (range, 19-71) and most patients (n=46, 87%) had a Karnofsky performance score ≥80%. Forty (73%) and 9 (16%) patients were in complete remission (CR) and partial remission (PR), respectively, at day 100 after ASCT1. Twenty-six (46%) relapsed within 12 months after ASCT1. Patients received a median of 1 (0-5) treatment lines between ASCT1 and ASCT2. Of note, only 2 patients received brentuximab vedotin after ASCT1 and none of the patients in our series received checkpoint inhibitors as salvage after ASCT1. The median interval from relapse/progression to ASCT2 was 9.7 months (1.7-89.3). At the time of ASCT2, 38 (69%) patients had chemosensitive disease (20 of them CR; and 18 PR). Most patients (n=43, 77%) received BEAM as the conditioning regimen for ASCT1, whereas preparative regimens for ASCT2 were more heterogeneous (BEAM or similar in 27, 48%; CBV or similar in 8, 14%; and others in 21, 37%). The median time to neutrophil (>0.5x109/L) and platelet (>20x109/L) recovery after ASCT2 were 11 (IQR 9-12) and 12 (IQR 10-15) days, respectively. Best response at day 100 following ASCT2 included CR in 29 (52%) patients and PR in 7 (12%); 3 (5%) had stable disease, and 3 (5%) progressed. Twenty-nine (52%) patients are currently alive, with a median follow-up for surviving patients of 73 months (2-153). Causes of death were HL progression (n=21, 79%), ASCT2 toxicity (n=3, 11%), secondary neoplasia (n=1, 3.7%), and unknown (n=2, 7%). The 4-year non-relapse mortality (NRM) was 5% (95% CI 1-14%). The 4-year cumulative incidence of disease progression/relapse was 69% (95% CI 54-80%). The 4-year overall survival (OS) and progression free survival (PFS) were 63% (95% CI 51-77%) and 25% (95% CI 16-41%). In univariate analysis, HL relapse within 12 months of ASCT1 was associated with a worse 4-year OS (44% vs. 79%, p=0.016) and PFS (16% vs. 33%, p=0.033). Chemosensitivity at ASCT2 predicted for better outcomes (4-year OS 78% vs. 30%, p=0.002; PFS 34% vs. 6%, p=0.004). Our series is the largest thus far reported of ASCT2 for patients with R/R HL after ASCT1. NRM is lower than that observed after allogeneic transplantation in this setting; however, relapse remains a major issue, especially for patients who relapse in less than one year after ASCT. For this population, a second ASCT should not be considered, whereas ASCT2 in patients with long response duration after ASCT1 might be appropriate in selected cases. The role of ASCT2 for those patients treated with new drugs such as brentuximab vedotin and checkpoint inhibitors deserves further investigation. Disclosures Martinez: BMS: Research Funding; Takeda: Consultancy. Sureda:BMS: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Merck: Consultancy, Honoraria.

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67 +/- 2%, 53 +/- 2%, and 40 +/- 2%, respectively. The non-relapse mortality rate at 2 years was 7 +/- 1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52 +/- 2% and 40 +/- 2%, respectively) and the 137 patients transplanted in second complete remission (58 +/- 5% and 35 +/- 5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63 +/- 4% in patients with good risk cytogenetics, 52 +/- 3% in those with intermediate risk cytogenetics, and 37 +/- 10% in those with poor risk cytogenetics (P=0.01); patients

Introduction: Patients infected with HIV have an increased risk of developing aggressive B-cell non-Hodgkin lymphoma and Hodgkin lymphoma (HL). The continuous development of cART during the last decade has improved the prognosis of HIV-associated lymphoma considerably. However, a significant proportion of these patients will experience lymphoma relapse and may be candidates for autoSCT. The purpose of the present study was to investigate if recent advances in anti-lymphoma therapy and anti-infectious strategies have influenced the outcome of autoSCT for HIV-related lymphoma. Patients and methods: For this retrospective study, all EBMT-registered patients aged 18 years or older with HIV-positive serostatus who were treated with a first autoSCT between 2007 and 2013 were eligible. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were requested to provide additional HIV and lymphoma treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression models. Curves of cumulative incidence of relapse (IR) and non-relapse mortality (NRM) were compared by Gray's test. Results: 138 patients from 25 European centers met the eligibility criteria and had the full data set required for this analysis available. 86% were male, median age was 44 years (range 24-69). Underlying diagnoses were diffuse large B cell lymphoma (DLBCL) in 46%, HL in 21%, Burkitt lymphoma in 14%, plasmablastic lymphoma (PBL) in 10%, and other lymphoma in 9% of the patients. Disease status at autoSCT was complete remission (CR) in 51%, partial remission (PR) in 33%, and less than PR in 16% of the patients, achieved after 1 (28%), 2 (58%), or more than 2 lines of chemotherapy (14%). With HIV load below the threshold of detection in 74% of the patients, the median CD4+ cell count was 187/µl (range 0-800) at transplant. 95% of the patients continued with cART during salvage and high-dose chemotherapy. BEAM was used as high-dose regimen in 77% of the patients. With a median follow-up of 4 years, 2-year NRM, IR, progression-free survival (PFS) and overall survival for the whole series were 9%, 23%, 68% and 70%, respectively. By multivariate analysis, diagnosis DLBCL or PBL (vs HL), increasing number of chemotherapy pretreatment lines, and less than PR at autoSCT were significant predictors of an unfavorable PFS; whilst age, high-dose regimen, performance status, and viral load had no significant impact. 2-year PFS in patients with 1st-line CR, later CR, PR, or less than PR at autoSCT was 91%, 80%, 64%, and 23%, respectively. Conclusions: This series, which is the largest ever on lymphoma transplants in HIV+ patients, suggests that in the cART / chemoimmunotherapy era, the outcome of autoSCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of HIV infection. AutoSCT under ongoing cART therapy remains the treatment of choice for HIV+ patients with PBL or recurrent DLBCL or HL. Disclosures Kröger: Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Montoto:Roche: Honoraria; Gilead: Research Funding. Dreger:Novartis: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy.