Role Of Autologous Stem Cell Transplantation Research Articles

Ten Years of Hematopoietic Stem Cell Transplantation in Patients with Light Chain Amyloidosis: Real World Data from a Health Center in Latin America

Background: Autologous stem cell transplantation (ASCT) is an effective treatment for patients with AL amyloidosis. In recent years, due to the advent of daratumumab-based regimens that achieve fast, deep, and long-lasting hematological responses, the role of ASCT and its optimal timing have been put in discussion. Access to ASCT in Latin America is difficult and specialized transplant centers are scarce, as is access to daratumumab-based chemotherapy regimens. Objectives: To describe the characteristics and evolution of patients with AL amyloidosis who received an autologous stem cell transplantation (ASCT) estimating organic response, overall and progression-free survival. To compare the evolution between patients initially eligible for transplantation and those who were not. Methods: We designed a retrospective cohort study of adult patients with AL Amyloidosis who received an ASCT between 2012 and 2022. Those who did not complete one year of follow-up were excluded. We obtained data from patients enrolled in the Institutional Amyloidosis Registry. Continuous variables were compared with the Student or Mann-Whitney test according to distribution, and categorical variables were compared with chi2 or Fisher. Overall and progression-free survival was estimated using Kaplan Meier. Results: Of 129 patients with AL, 32 received ASCT (24.5%). Twenty were eligible for analysis.The baseline characteristics are shown in table 1. The median time to diagnosis was 14 months (IQR 7-27). At the time of diagnosis, 9 patients (45%) were not eligible for transplantation; in all cases, ineligibility was due to cardiac involvement, with 4 receiving heart transplantation prior to ASCT. The longest time between heart transplantation and ASCT was 348 days. More information on renal and cardiac involvement at diagnosis and at ASCT is shown on table 2. Regarding treatment, 18 patients underwent a single line of chemotherapy with a median of 4 cycles prior to ASCT. All patients received regimens with bortezomib and only 3 added daratumumab. One patient underwent ASCT without hematological response, 7 with a partial response (PR), 5 with very good partial response (VGPR) and 7 with a complete response (CR). The time to best hematological response was not statistically different between patients who did and did not receive daratumumab, probably due to the low number of patients in the daratumumab group. The median age at transplant was 63.5 years old (IQR 50.5-68). Fourteen patients underwent conditioning with full dose melphalan and 6 with reduced dose. There was no statistically significant difference between these groups in terms of relapse and survival. The median number of days of hospitalization for the transplant was 20 (IQR 18-24). Only two patients required intensive care. The median number of transfusions per patient was 5 (IQR 3-9). There were no deaths during hospitalization or in the first 100 days of followup. The median time to engraftment was 12.5 days (IQR 11-14); in patients with cd34 collects > 6.5x10(6), median time to engraftment was 12.2 days (IQR 10.6-13.8), and in patients with cd34< 6.5x10(6), 15.4 days (IQR 9.9-20.9). This difference, as well as the difference in transfusions among the two groups, was not statistically significant. After ASCT, 15 patients obtained CR and 5 VGPR; 8 patients relapsed. The median time to relapse was 6.10 years (IQR 2.28-6.70). Of 9 patients with renal involvement, 7 presented renal response (2 pre and 5 post ASCT). Of the remaining, 1 received a post ASCT kidney transplant. Median time to renal response from start of treatment was 740 days (IQ 400-1736). Amongst the 10 patients with cardiac involvement, 4 underwent pre-ASCT heart transplantation. Of the remaining, 5 (83%) documented cardiac responses with a median of 538 days (IQR 487-611), in 2 cases prior to ASCT. There were no differences in morbidity and mortality between heart transplant recipients and the ones who did not receive a heart transplantation. Only 3 patients died, 2 from causes related to cardiac involvement and one from unrelated causes. Conclusions: ASCT is a safe treatment when performed in an experienced center. It ensures deep responses and prolongs progression-free survival. Patient selection is key to achieve these outcomes. Ineligibility at diagnosis is not related to worse post ASCT morbidity and mortality outcomes. Heart transplantation prior to ASCT is a safe strategy to favor eligibility.

Role of Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma in the First Complete or Partial Remission: A Propensity Score-Matched Analysis

Background Consolidation with autologous stem cell transplantation (ASCT) was recommended for most responders to the initial peripheral T-cell lymphoma (PTCL) treatment. Evidence came primarily from retrospective studies affected by a selection bias between patients allocated to receive ASCT or not and a few prospective studies with no control groups (d'Amore F,2012; Ellin F, 2014). The National Comprehensive Cancer Network and the American Society for Transplantation and Cellular Therapy (ASTCT) recommend ASCT for patients with first-time complete remission (CR1). The European Society of Medical Oncology (ESMO) guidelines suggest that patients with first-time partial remission (PR1) could also be considered for ASCT (d'Amore F, 2015). However, the role of ASCT in patients with PTCL after CR1 or PR1 remains controversial. The COMPLETE study showed an insignificant tendency for better survival following ASCT in the PTCL with CR1 group (Park SI, 2016). The LYSA multicenter study investigated the effect of ASCT in patients with CR1 or PR1. Neither propensity score matching (PSM) nor Cox multivariate analysis supported the advantage of ASCT in upfront consolidation (Fossard G, 2018). However, well-designed randomized controlled trials to investigate the precise effect of ASCT in the front-line setting are lacking. Therefore, we aimed to investigate the efficacy of ASCT for PTCL with CR1 and PR1 by PSM analysis. Methods We pre-screened 8 826 patients with lymphoma admitted to Peking University, Cancer Hospital & Institute from January 1996 to November 2020. Patients with mature T/NK cell lymphomas were selected (n = 1 136). We excluded patients with NK/TCL or missing clinical data. Response assessment to the initial treatment was evaluated by 18F-FDG positron emission tomography/computed tomography (PET/CT) or CT using the Lugano criteria. We identified 685 patients with PTCL, of which 622 achieved CR1 or PR1. PSM was used to balance clinical indicators between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Results Among the 622 patients who underwent initial therapy, 272 (43.7%) achieved CR1, and 147 (23.6%) achieved PR1 after the treatment. After excluding 5 patients with subsequent unknown schemes following the initial treatment, 414 were included in the final analysis (ASCT, n = 73; non-ASCT, n = 341). With a median follow-up of 5.7 years for the entire cohort, long-term survival in the ASCT group was better than in the non-ASCT group (median EFS, 8.1 vs. 2.8 years, P = 0.002; median OS, 14.9 vs. 10.2 years; P = 0.007). The 5-year EFS and OS were 66.7% (95% CI, 56.0-79.4%) and 74.7% (95% CI, 64.1-87.0%) in patients with ASCT consolidation, and 26.6% (95% CI, 23.0-30.8%) and 43.6% (95% CI, 39.2-48.4%) in patients without ASCT. After PSM, the ASCT and non-ASCT groups were similar in their disease subtypes, LDH level, Ann Abor stage, and the response to the initial treatment. The survival advantage for ASCT (n = 46), as a consolidation procedure, over non-ASCT (n = 84; median EFS. 8.1 vs 2.7 years, P = 0.007; median OS, not reached vs 7.7 years; P = 0.022; Figure 1) was maintained even after PSM. For the entire cohort, ASCT was associated with better long-term survival than non-ASCT [hazard ratio (HR) for EFS, 0.46 (95% CI, 0.28-0.76), P = 0.003; HR for OS, 0.50 (95% CI, 0.31-0.84), P = 0.008)]. Subgroup analysis showed that patients at a higher risk based on International Prognostic Index (IPI) stratifications and advanced stages might benefit significantly from ASCT. Patients with angioimmunoblastic T-cell lymphoma (AITL) in the ASCT group appeared to show better survival than those in the non-ASCT group (EFS: HR, 0.26; 95% CI, 0.10-0.66; P = 0.005; OS: HR, 0.29; 95% CI, 0.12-0.74; P = 0.009). However, ASCT endowed no survival advantage for other PTCL subtypes. Conclusion ASCT could improve the long-term survival of responders to the initial treatment among patients with PTCL, especially those with AITL. However, the specific population that could benefit most from up-front ASCT needs to be characterized further. Figure 1. EFS (A) and OS (B) after propensity score matching in the ASCT and non-ASCT groups Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Recent guidelines for high dose chemotherapy and autologous stem cell transplant for systemic AL amyloidosis: a practitioner’s perspective

Introduction High dose melphalan followed by autologous stem cell transplant (ASCT) has been transformative in treating AL amyloidosis since the early nineties. Recently, the European Haematology Association (EHA) and International Society of Amyloidosis (ISA) have developed a combined guideline for the management of patients undergoing an ASCT for AL amyloidosis. Areas covered In this practitioner’s perspective, we review the guideline, focussing on 6 major areas and offer practical advice for its application. We provide a perspective on the optimal use of ASCT and its potential application in the future. Expert opinion The EHA-ISA guideline comprehensively outlines the practicalities of performing an ASCT in AL amyloidosis. The critical aspect is careful patient selection. Vigilant fluid balance assessments are crucial as associated complications are common and dangerous. The role of ASCT is changing with improving haematological responses associated with novel agents. Evidence is limited for the use of ASCT in patients who achieve a complete haematological response (CR). Therefore, ASCT should be considered for those who only achieve a very good partial response (VGPR)/partial response (PR) and fulfil the strict selection criteria. Future research identifying the cohort who would benefit most from ASCT in the era of novel therapies is warranted.

Advances in the treatment of light chain amyloidosis.

After many years, the management of systemic light chain (AL) amyloidosis is entering the era of evidence-based medicine, with three recently published randomized clinical trials, a regimen (daratumumab, cyclophosphamide, bortezomib, and dexamethasone, daratumumab-CyBorD) labeled for upfront therapy, more clinical trials ongoing, and published guidelines. In this review, we discuss how current practice is changing based on this data. Daratumumab-CyBorD grants unprecedentedly high rates of hematologic and organ response and became the novel standard-of-care in AL amyloidosis. The International Society of Amyloidosis and the European Hematology Association issued common guidelines for autologous stem cell transplant (ASCT) in this disease. Improved patient selection and effective induction regimens greatly reduced ASCT-related mortality. Venetoclax is emerging as a very effective option in patients harboring the common t(11;14) abnormality. Rapid and profound reduction of the amyloid free light chain can improve survival also at advanced stages. Daratumumab-CyBorD is being integrated into the treatment flow-chart whereas the role of ASCT is being redefined. New approaches are being tested in clinical trials. Treatment of daratumumab-refractory patients and validation of criteria of hematologic progression to be used in clinical trials and in individual patient management are current areas of research.

Treatment Outcomes and Roles of Transplantation and Maintenance Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts.

Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR). Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of 1,168 patients from 12 academic centers. Among 3,614 patients with documented 1L treatment, BR was the most used. Among 1,265 patients age < 65 years, 30.5% received cytarabine-based induction and 23.5% received ASCT. There was no significant association between ASCT and real-world time to next treatment (hazard ratio [HR], 0.84; 95% CI, 0.68 to 1.03; P = .10) or overall survival (HR, 0.86; 95% CI, 0.63 to 1.18; P = .4) among ASCT-eligible patients. Among MR-eligible patients, MR after BR versus BR alone was associated with a longer real-world time to next treatment (HR, 1.96; 95% CI, 1.61 to 2.38; P < .001) and overall survival (HR, 1.51; 95% CI, 1.19 to 1.92; P < .001). The efficacy findings were consistent in the validation cohort. In this large cohort of patients treated primarily in the US community setting, only one in four young patients received cytarabine or ASCT consolidation, suggesting the need to develop treatments that can be delivered effectively in routine clinical practice. Together with the validation cohort, data support future clinical trials exploring regimens without ASCT consolidation in young patients, whereas MR should be considered for patients after 1L BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplant (ASCT) for Patients with POEMS Syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin Changes): A CIBMTR Analysis

IntroductionPOEMS syndrome is a rare disease associated with a plasma cell dyscrasia with limited information regarding the role of ASCT. Small single institution series have demonstrated deep and durable responses after ASCT along with neurological improvement. Despite these benefits, ASCT is thought to have higher treatment related morbidity and mortality, limiting its use. We describe the outcomes from an international multicenter database of patients with POEMS syndrome undergoing ASCT.MethodsWe performed a retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database to evaluate the outcomes of patients undergoing ASCT for POEMS syndrome. Standard descriptive methods were used to report patient characteristics. Univariate and multivariate analysis were performed to identify predicators for non-relapse mortality (NRM), relapse, progression-free and overall survival (PFS, OS). NRM was compared between POEMS and multiple myeloma (MM) patients who underwent ASCT during the same time period.ResultsBetween 2008-2018, 331 pts with POEMS syndrome who underwent ASCT were identified. The median age was 51 years, with 66% males. Racial distribution was 65% Caucasians, 19% African American, 5% other, and 10% missing. Pre-transplant characteristics included 70% patients had Karnofsky score <90, and 50% had HCT-CI ≥ 3, reflecting underlying disease severity and symptoms. The most common comorbidity was pulmonary (52%). Only 14% of patients were in very good partial response or better at the time of ASCT and 72 (22%) patients underwent ASCT without prior treatment. The median time from diagnosis to ASCT was 7 months and 74% underwent ASCT within 12 months of diagnosis. The most common mobilization strategy was GCSF +/- plerixafor in 50% of pts and 87% of pts received conditioning with 200mg/m2 of Melphalan. The median follow up was 48 (range 3-137) months. At day 100, NRM was 0.9 % (95% CI: 0.2-2.2%). At 4 years, NRM was 4.9% (95% CI: 2.6-7.9%), relapse 15.4% (95% CI 11.3-20.1%), PFS 79.7% (95% CI 74.5-84.3%) and OS 92% (95% CI 89.2-95.6%). Subsequent neoplasms were seen in 16 (5%) with 4 myeloid malignancy and 12 solid tumors. On multivariate analysis, age ≥ 60 years was associated with greater hazards of mortality, HR 2.6 (95% CI 1.2-5.6), p 0.01. The figure shows the comparable NRM between POEMS and MM (p 0.31).Conclusions:We report outcomes of the largest ASCT series of POEMS patients. Despite a high HCT-CI and low functional status among patients with POEMS syndrome, no difference in NRM was seen when compared to MM. Post-transplant outcomes were excellent and support single center data on the role of ASCT in this rare disease. [Display omitted] DisclosuresKansagra: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Alynylam: Membership on an entity's Board of Directors or advisory committees; Cota Health: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Dispenzieri: Alnylam: Research Funding; Pfizer: Research Funding; Sorrento Therapeutics: Consultancy; Takeda: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Kumar: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; BMS: Consultancy, Research Funding; Oncopeptides: Consultancy; Beigene: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Novartis: Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Carsgen: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Qazilbash: Bristol-Myers Squibb: Other: Advisory Board; NexImmune: Research Funding; Janssen: Research Funding; Biolline: Research Funding; Oncopeptides: Other: Advisory Board; Angiocrine: Research Funding; Amgen: Research Funding. Shah: GSK: Consultancy; Karyopharm: Consultancy; Oncopeptides: Consultancy; Indapta Therapeutics: Consultancy; Janssen: Research Funding; Nektar: Research Funding; Bluebird Bio: Research Funding; Teneobio: Research Funding; CareDx: Consultancy; BMS/Celgene: Research Funding; Sanofi: Consultancy; Sutro Biopharma: Research Funding; CSL Behring: Consultancy; Poseida: Research Funding; Precision Biosciences: Research Funding; Amgen: Consultancy; Kite: Consultancy. D'Souza: Sanofi, Takeda, Teneobio, CAELUM, Prothena: Research Funding; Imbrium, Pfizer, BMS: Membership on an entity's Board of Directors or advisory committees; Janssen, Prothena: Consultancy.

The role of autologous stem-cell transplantation in multiple myeloma in 2021.

In this review, we discuss the most important aspects of the role of high-dose melphalan (HDM) and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM). Almost 40 years after the publication of the first study on safety and efficacy of HDM and ASCT in MM patients, and despite the introduction of several drugs and combinations with various targets on the plasma cell and the surrounding microenvironment, HDM-ASCT still stands as a standard of care for the upfront treatment of newly diagnosed MM patients. Indeed, all attempts to replace HDM-ASCT with novel-agent-based, non-transplant strategies have failed to demonstrate their efficacy, at least in terms of progression-free survival. Despite such a long history in MM, a number of open issues regarding HDM-ASCT still exist, from the choice between using transplant in first-line therapy or at relapse to the use of tandem HDM-ASCT in high-risk patients. With the introduction of more and more effective multidrug regimens and of novel immunotherapeutic approaches, the challenge between transplant and non-transplant is not over yet.

The value of complete remission according to positron emission tomography prior to autologous stem cell transplantation in lymphoma: a population-based study showing improved outcome

BackgroundChimeric antigen-receptor T-cell and bispecific antibody therapies will likely necessitate a reconsideration of the role of autologous stem-cell transplantation (ASCT) in lymphoma. Patients who are likely to profit from ASCT need to be better identified.MethodsHere, we investigated the value of positron emission tomography/computerized tomography (PET/CT) before ASCT. All 521 patients transplanted for lymphoma 1994–2019 at Karolinska (497 conditioned with BEAM) were included.ResultsOutcome improved over three calendar periods 1994–2004, 2005–2014, 2015–2019 (2-year overall survival [OS]: 66, 73, 83%; P = 0.018). Non-relapse mortality (NRM) at 100 days over the three periods were 9.8, 3.9, 2.9%, respectively. The OS improvement between 1994 and 2004 and 2005–2014 was due to lower NRM (P = 0.027), but the large OS advance from 2015 was not accompanied by a significant reduction in NRM (P = 0.6). The fraction of PET/CT as pre-ASCT assessment also increased over time: 1994–2004, 2%; 2005–2014, 24%; 2015–2019, 60% (P < 0.00005). Complete responses (PET/CT-CR) were observed in 77% and metabolically active partial responses (PET/CT-PR) in 23%. PET/CT-CR was a predictor for survival in the entire population (P = 0.0003), also in the subpopulations of aggressive B-cell (P = 0.004) and peripheral T-cell (P = 0.024) lymphomas. Two-year OS and progression-free survival (OS/PFS) for patients in PET/CT-CR were in relapsed/refractory aggressive B-cell lymphoma 87%/75% and peripheral T-cell lymphoma 91%/78%. The corresponding figures in PET/CT-PR were 43%/44 and 33%/33%. Patients with solitary PET/CT-positive lesions showed acceptable outcome with ASCT followed by local irradiation (2-year OS/PFS 80%/60%). CT was less discriminative: 2-year OS/PFS: CT-CR, 76%/66%; CT-PR, 62%/51%. Outcome was inferior after BEAC compared with BEAM conditioning.ConclusionsWe conclude that the improved outcome reflects better, PET/CT-informed, identification of patients who should proceed to ASCT. The excellent survival of patients in PET/CT-CR indicates that ASCT should remain part of standard therapy for lymphoma.

The initial management of multiple myeloma in the era of novel agents: 2021 and beyond.

The initial management of multiple myeloma in the era of novel agents: 2021 and beyond.

Invited Review: Will Consolidation with ASCT Be a Thing of the Past for MCL and PTCL?

The treatment landscape of mantle cell (MCL) and peripheral T-cell lymphomas (PTCL) is rapidly changing; however, despite improvement in patients' survival, they still remain a largely incurable diseases. Treatment choice is dependent on patient factors, prior therapy, remission duration, and candidacy for stem cell transplantation (SCT). There are subsets of high-risk patients who do not benefit substantially from autologous SCT (ASCT) and for whom alternative targeted approaches are being examined. Here, we critically analyze the actual role of ASCT in PTCL and MCL. Research in areas of maintenance therapy and minimal residual disease is ongoing to identify MCL patients who may not require ASCT for durable response. Moreover, there are subsets of high-risk MCL patients who do not benefit substantially from ASCT and for whom alternative, targeted approaches are being examined. Much less clear evidence exists regarding the impact of consolidative ASCT in PTCL, mainly for the heterogeneity of these lymphomas: it is still controversial whether patients who achieved a complete response significantly take advantage of this procedure over active surveillance only. Several clinical and biologic markers are available to predict prognosis; however, despite improvements in outcomes, standard therapeutic approaches have not been able to overcome high-risk disease features for PTCL and MCL. Thus, the need of ASCT for these diseases is still matter of debate among hematologists.

The Role of Autologous Stem-Cell Transplantation in High-Risk Neuroblastoma Consolidated by anti-GD2 Immunotherapy. Results of Two Consecutive Studies.

Background: Treatment of HR-NB comprise induction, consolidation with autologous stem cell transplant (ASCT) followed by anti-GD2 immunotherapy and isotretinoin. Childrens Oncology Group and SIOPEN studies used dinutuximab and cytokines to treat patients in complete remission or refractory Bone/Bone marrow (B/BM) disease after ASCT. Methods: HR-NB patients referred to Hospital Sant Joan de Déu for anti-GD2 immunotherapy were eligible for two consecutive studies (dinutuximab for EudraCT 2013–004864–69 and naxitamab for 017–001829–40) and naxitamab/Sargramostim CU with or without prior ASCT. Patients enrolled in first complete remission or with primary refractory B/BM disease. We accrued a study population of two groups whose therapy, aside from ASCT, was similar. This is a retrospective analysis of their outcome calculated from study entry. Results: From December 2014–2019, 67 patients were treated with dinutuximab and cytokines (n = 21) in the Hospital Sant Joan de Déu-HRNB-Ch14.18 study or with naxitamab and Sargramostim either in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM (11 with dinutuximab and 12 with naxitamab), and 44 in first CR (10 with dinutuximab and 34 with naxitamab). Study patients included 13 (19.4%) treated following single ASCT and 54 following conventional chemotherapy. Median follow-up for all patients is 16.2 months. Two-year rates for ASCT and non-ASCT patients were, respectively, EFS 64.1% vs. 54.2% (p = 0.28), and OS 66.7% vs. 84.1% (p = 0.81). For the 44 pts in first CR, 2-years rates for ASCT and non-ASCT patients were, respectively, EFS 65.5% vs. 58.7% (p = 0.48), and OS 71.4% vs. 85.4% (p = 0.63). Conclusions: In this retrospective, single center study, ASCT did not provide survival benefit when anti-GD2 immunotherapy was used after induction chemotherapy.

The role of autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy: Results of 2 consecutive studies in a single referral institution.

10539 Background: Treatment of high-risk NB within the major international cooperative groups (COG and SIOP) comprise intensive induction, consolidation with high dose chemotherapy and autologous stem cell rescue (ASCR) followed by anti-GD2 immunotherapy and isotretinoin as maintenance therapy. In the COG studies dinutuximab and cytokines (GM-CSF and IL-2) were used to treat patients in complete remission (CR) after ASCR whereas SIOPEN studies used dinutuximab-beta plus/minus IL-2 and included patients with responsive (no progression 109 days after ASCR) but refractory (skeletal metaiodobenzylguanidine positivity with three or fewer areas of abnormal uptake). Methods: Since December 2014, HR-NB patients referred to HSJD were eligible for consolidation with anti-GD2/GM-CSF immunotherapy in 2 consecutive studies (dinutuximab for EudraCT 2013-004864-69 and naxitamab for 017-001829-40) and naxitamab/GM-CSF compassionate use (CU) with or without prior ASCR. Patients were enrolled in 1st CR or with primary refractory bone/bone marrow (B/BM) disease. We accrued a study population of two groups whose consolidative therapy, aside from ASCR, was similar: anti-GD2 (dinutuximab or naxitamab) antibodies + GM-CSF and local radiotherapy. This is a retrospective analysis of their event-free survival (EFS) and overall survival (OS) calculated from study entry. Results: From Dec 14 til Dec 19, 67 study patients were treated with the COG (dinutuximab + GM-CSF+ IL-2 + RA) regimen (n = 21) in the HSJD-HRNB-Ch14.18 study or with Naxitamab and GM-CSF in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM, and 44 in 1st CR. The 67 study patients included 13 (19%) treated following single ASCR and 54 following induction chemotherapy and surgery. Median follow-up for all surviving patients is 16.2 months. Two-year rates for ASCR and non-ASCR patients were, respectively: EFS 64% vs. 54% (p = 0.28), and OS 66.7% vs. 84% (p = 0.8). For the 44 pts in 1st CR, 2-year rates for ASCR and non-ASCR patients were, respectively: EFS 65% vs. 58% (p = 0.48), and OS 71% vs. 85% (p = 0.63). Conclusions: In this retrospective, single center study, ASCR did not provide survival benefit when anti-GD2 + GM-CSF based immunotherapy was used for consolidation after dose-intensive conventional chemotherapy.

Application progress of autologous stem cell transplantation in lymphoma treatment

In recent years, due to the progress of cell-targeted therapy and the presence of a large number of new drugs, the treatment efficacy and survival of many lymphoma patients have improved. As a traditional treatment method, autologous stem cell transplantation (ASCT) still plays an important role in lymphoma treatment. ASCT can be a curable method in some clinical situations. Many clinical studies in recent years have further confirmed the role of ASCT in high-risk aggressive lymphoma and Hodgkin lymphoma. The efficacy of ASCT can be improved by combining antibodies such as brentuximab vedotin, programmed death 1, programmed death ligand 1 or chimeric antigen receptor T cell therapy, and the recurrence risk of ASCT may be decreased. Key words: Lymphoma; Stem cell transplantation; Immunotherapy

PF752 AUTOLOGOUS STEM CELL TRANSPLANT CONDITIONING WITH CHIDAMIDE, CLADRIBINE, GEMCITABINE AND BUSULFAN AS CONSOLIDATION MAY OVERCOME POOR PROGNOSIS OF PATIENTS WITH DOUBLE EXPRESSER LYMPHOMA

Background:Double‐protein‐expression lymphomas (DEL) is a unique sub‐group of diffuse large B‐cell lymphoma (DLBCL) with co‐expression of MYC and BCL‐2 on immunohistochemistry. Compared with classic DLBCL, DEL has a lower response to standard induction chemoimmunotherapy with rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) and poorer prognosis. Autologous stem cell transplant (ASCT) is a potentially curative treatment of high‐risk of relapsed/refractory lymphomas. However, the role of ASCT in patients with DEL is controversy. Our pre‐clinic and clinic studies showed the combination of chidamide, cladribine, gemcitabine and busulfan (ChiCGB) worked synergistically against lymphomas.Aims:So, in this study, we used ASCT conditioning with ChiCGB as consolidation in patients with DEL in first or second complete remission.Methods:This study was a phase 2 trial done at the West China Hospital of Sichuan University from May. 2016 to Dec. 2018. Eligible patients were aged 16–65 years and had received R‐CHOP or chidamide‐R‐CHOP as first‐line or any second‐line therapies. They achieve first or second complete remission (CR) before transplant. The DEL was diagnosed as MYC expression ≥ 40% and BCL‐2 ≥ 50% on immunohistochemistry. Additional eligibility criteria were an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, adequate major organs function, no active hepatitis bacteria, fungal or virus infection. Patients provided written informed consent to participate in the trial. Patients with DLBCL without MYC and BCL‐2 over‐expression were assigned to the control group (non‐DEL).Patients received ChiCGB conditioning regimen consisting of oral chidamide 30 mg on days −7, −4, 0, +3, intravenous cladribine at a dose of 6 mg/m2 from days −6 to −2, intravenous gemcitabine 4 hours after cladribine at a dose of 2500 mg/m2 on days −6 and −2, and intravenous busulfan at a fixed dose of 3.2 mg/kg from days −6 to −2. Dexamethasone was prophylactically given for adverse effect of high dose gemcitabine from the day −6 to −2. Peripheral‐blood stem‐cells were infused on day 0.Results:A total of 44 patients with DLBCL were enrolled, with 22 DEL and 22 non‐DEL. The median age was 46 (range, 23 to 61) and 34.5 (range, 16 to 61) years in DEL and non‐DEL groups. There were 8 (36.3%) and 12 (54.5%) patients in second CR in DEL and non‐DEL group respectively. In DEL group, 5 patients receive chidamide‐R‐CHOP as first‐line therapy. Stem cells source was peripheral blood. Median infused CD34+cells count was 2.2 × 106/Kg (range, 1.0 to 11.6 × 106/Kg). Neutrophils and platelets were engrafted on a median day +10 (+8 to +14) and day +12 (range, days +8 to +38), respectively. The median follow‐up was 17.8 (range, 4.1 to 34.9) and 20 (range, 3 to 46.3) months in DEL and non‐DEL group. The 2‐year progression free survival of patients with DEL or non‐DEL was 94.4% and 84.2% (P = 0.3731), while the 2‐year overall survival of tow groups was 94.1% and 100% (P = 0.2904) (Figure‐1).Summary/Conclusion:Our study showed ChiCGB efficiently prevented relapse of DEL. Compared with the survival of patients with non‐DEL, ChiCGB with ASCT may overcome poor prognosis of patients with diffuse large B‐cell lymphoma with co‐expression of MYC and BCL‐2.image

Bortezomib Maintenance (BM) or Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): 8 Year Follow up of CALGB 50403 (Alliance)

Bortezomib Maintenance (BM) or Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): 8 Year Follow up of CALGB 50403 (Alliance)

Survival outcomes of patients with primary plasma cell leukemia (pPCL) treated with novel agents.

Primary plasma cell leukemia (pPCL) is an aggressive plasma cell disorder characterized by circulating plasma cells and a poor prognosis. Although patients who have pPCL benefit from the use of stem cell transplantation (SCT) and novel agents, their prognosis remains inferior to that of patients who have myeloma. This was a retrospective analysis of 38 consecutive patients with pPCL who were diagnosed between October 2005 and July 2016 and were registered in the Winship Cancer Institute of Emory University database. Baseline characteristics as well as data about treatment and survival outcomes were collected. The median patient age at diagnosis was 58 years. All patients received a bortezomib-based induction regimen, and 92% received both bortezomib and an immunomodulatory drug (thalidomide or lenalidomide); in addition, 74% of patients underwent autologous SCT (ASCT), and 61% received maintenance therapy. The best response to first-line therapy was a partial response or better in 87% of patients, and 45% had a complete response (CR). The achievement of ≥CR was a predictor for prolonged progression-free survival (PFS) and overall survival (OS). The median PFS was 20 months, and the median OS was 33 months. PFS was prolonged in patients who underwent ASCT compared with those who did not undergo ASCT (25 vs 6 months; P = .004), and patients who received maintenance therapy after ASCT had prolonged median PFS (27 vs 11 months; P = .03) and a trend toward prolonged OS (median, 38 vs 22 months; P = .06) compared with those who did not receive maintenance therapy. The current data support the use of regimens combining novel agents in the upfront treatment of patients with pPCL as well as the role of ASCT and maintenance therapy for long-term disease control.

Stem Cell Transplantation in Multiple Myeloma.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT. Moreover, the positive results obtained with these agents in consolidation and maintenance strategies after ASCT strongly support the concept of continuous therapy, whose ultimate goal is the long-term control of the disease and the improvement of outcome. Preliminary data from studies investigating next generation proteasome inhibitors, such as carfilzomib and ixazomib, used upfront as well as at subsequent therapeutic lines, demonstrate the possibility of achieving molecular remission in most of the patients. The deeper responses obtained with new drugcombinations questioned the role of ASCT, and large, ongoing, phase 3 trials will shed light on the role and the timing of ASCT.

Autologous peripheral blood stem cell transplantation and the role of lenalidomide in patients affected by poems syndrome.

POEMS syndrome is a rare paraneoplastic condition, with a poorly understood pathogenesis. High dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been reported to be an effective therapeutic option for patients with good performance status. Here, we review the role of ASCT for POEMS syndrome and discuss indications together with advantages and disadvantages, and related issues such lenalidomide given before or after ASCT, VEGF levels as a marker of disease, and different regimens for stem cell mobilization.

The role of stem cell transplant for lymphoma in 2017.

The role of stem cell transplant for lymphoma in 2017.

Prolonged Progression-Free Survival Is Possible in Patients with Diffuse Large B-Cell Lymphoma Receiving > 1 Salvage Therapies before Autologous Stem Cell Transplant

IntroductionWhile 50-60% of patients with diffuse large B-cell lymphoma (DLBCL) are cured with initial chemoimmunotherapy such as R-CHOP, many patients will relapse and require additional therapy. Historically, autologous stem cell transplant (ASCT) has been utilized in chemo-sensitive patients with relapsed DLBCL although the role of ASCT in patients who require > 1 salvage treatment to achieve remission is less defined due to concerns about the likelihood of long-term remission in that population. We evaluated the outcome of ASCT in patients who required >1 salvage therapy.MethodsWe included all patients undergoing ASCT for relapsed/refractory DLBCL at our site between 2005-2016 who received > 1 salvage treatment before transplant, with radiation therapy considered a salvage treatment if given after relapse but before ASCT. We collected demographic, clinical, laboratory and pathologic data on all patients. We defined progression-free survival (PFS) as time from ASCT to date of progression or death from any cause and overall survival (OS) as time from ASCT to date of death from any cause. Living patients were censored at the time of their last follow up. Univariate Cox proportional hazards models of PFS and OS were fit and Kaplan-Meier plots were developed to estimate the impact of variables of interest on survival.ResultsOut of 259 patients undergoing ASCT for DLBCL, 43 received > 1 salvage treatment, the median age was 51 years and 23 patients were male. Twenty patients had stage III/IV disease at diagnosis. The median time to relapse from the time of diagnosis was 9.3 months, and 42% of patients experienced a relapse > 12 months after diagnosis. Twenty-six patients (60%) received radiation as one of their salvage therapies, 25 patients (58%) received R-ICE as their first salvage therapy and 10 (23%) patients received R-ICE as their second salvage treatment. All patients received either 2 (n=39) or 3 (n=4) salvage therapies before ASCT, and the response to the initial salvage therapy received was CR in 4 patients, PR in 14 patients, SD in 1 patient, and PD in 14 patients, with initial response to salvage therapy missing in 10 patients. The median PFS for all patients was 15.9 months and the median OS was 57.2 months (Figure 1a). Receipt of radiation and having disease sensitive to treatment at the time of ASCT were the only factors associated with prolonged PFS and OS. Median PFS has not been achieved in patients who received radiation while patients who did not receive radiation had a median PFS of 4.2 months (HR = 0.36, p = 0.014; Figure 1b). Patients who had a chemo sensitive disease status at transplant had a median PFS of 22.6 months; however, patients with refractory disease at transplant only achieved a median PFS of 3.6 months (HR = 0.30, p=0.008). Remaining factors including conditioning regimen, time to relapse, and number of salvage therapies were not significantly associated with PFS or OS.ConclusionsASCT can result in prolonged PFS/OS in patients requiring > 1 salvage therapy especially in the case of sensitive disease. Radiation as an additional line of therapy is associated with improved PFS/OS, suggesting this can be included to induce remission in patients who fail to achieve CR with initial salvage treatment. While uncommon, patients with chemo-refractory disease can also have durable survival and should not be excluded from transplant. [Display omitted] [Display omitted] DisclosuresCalzada:Seattle Genetics: Research Funding. Flowers:Spectrum, Janssen, Infinity, AbbVie, Acerta, Pharmacyclics, TG Therapeutics: Research Funding; Celgene Corporation: Consultancy, Honoraria; Optum Rx, Seattle Genetics, Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Seattle Genetics: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.