Autologous Stem Cell Transplantation Group Research Articles

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Upfront Autologous Stem Cell Transplant at First Complete Remission in Patients with Advanced-Stage Extra-Nodal NK/T Cell Lymphoma: A Multicenter Retrospective Study

Objective: Treatment outcome of patients with advanced-stage extranodal NK/T cell lymphoma (NKTCL) remains unsatisfactory. The role of consolidation therapy with autologous stem cell transplantation (ASCT) at first complete remission (CR1) in these patients is controversial. This study aimed to investigate the effect of upfront ASCT on the prognosis of patients with advanced-stage NKTCL achieving CR1 to frontline therapy. Methods:This is a multicenter retrospective study. Data were collected from patients diagnosed with NKTCL between 2006 and 2021 in the China Lymphoma Collaborative Group (CLCG) database. The inclusion criteria were as follows: pathologically confirmed diagnosis of NKTCL, age≤65 years at diagnosis, stage III or IV disease, and achievement of CR1 at the completion of frontline induction therapy. Clinical characteristics, treatment including the use of ASCT, and follow-up information were reviewed. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: A total of 99 patients from 14 medical centers in China were included in this study. The median age was 38 years (range: 6-64 years). Sixteen patients (16%) had an ECOG-PS≥2 at diagnosis, and 26 patients (26%) presented with primary extra-nasal disease. The baseline Prognostic Index for NK-cell lymphoma (PINK) was≥2 in 63 patients (64%). Regarding first-line treatment, 85 patients (86%) received non-anthracycline-based chemotherapy, and the remaining patients received anthracyline-based chemotherapy. At the time of CR1, 32 patients (32%) received upfront ASCT consolidation and 67 patients did not. Baseline clinical characteristics were comparable between the ASCT group and non-ASCT group. With a median follow-up time of 33 months, median PFS was not reached in the ASCT group versus 46 months in the non-ASCT group (3-year PFS: 76.6% versus 54.9%, P=0.012). OS was not significantly different between the ASCT group and the non-ASCT group (3-year OS: 85.2% versus 69.4%, P=0.098). In multivariate analyses, upfront ASCT was independently associated with better PFS (HR=0.40, 95%CI 0.17-0.94, P=0.037) after adjusting for baseline PINK score and types of first-line chemotherapy (anthracyline-based versus non-anthracyline-based). Only non-anthracyline-based first-line chemotherapy (HR=0.32, 95%CI 0.11-0.88, P=0.028) was associated with better OS in multivariate analysis. Conclusions: In this multicenter real-world study, upfront ASCT improves PFS of patients with advanced stage NKTCL achieving CR1 to front-line chemotherapy, but the effect of upfront ASCT on OS in the era of non-anthracycline-based chemotherapy remains uncertain. The specific subgroups of patients most likely to gain a survival benefit from upfront ASCT need to be further investigated.

Cancer-specific mortality in multiple myeloma: a population-based retrospective cohort study.

Survival has improved in patients diagnosed with multiple myeloma (MM) over the last two decades; however, there remains a paucity of data on the causes of death in MM patients and whether causes of death change during the disease trajectory. We conducted a retrospective population-based study to evaluate the rates of MM-specific versus non-MM cause of death and to identify factors associated with cause-specific death in MM patients, stratified into autologous stem cell transplant (ASCT) and non-ASCT cohorts. A total of 6,677 patients were included, 2,576 in the ASCT group and 4,010 in the non-ASCT group. Eight hundred and seventy-three (34%) ASCT patients and 2,787 (68%) non-ASCT patients died during the follow-up period. MM was the most frequent causes of death, causing 74% of deaths in the ASCT group and 67% in the non-ASCT group. Other cancers were the second leading causes of death, followed by cardiac and infectious diseases. Multivariable analysis demonstrated that a more recent year of diagnosis and novel agent use within 1 year of diagnosis were associated with a decreased risk of MM-specific death, whereas a history of previous non-MM cancer, older age, and the presence of CRAB criteria at diagnosis increased the risk of non-MM death. Our data suggests that despite improvement in MM outcomes in recent years, MM remains the greatest threat to overall survival for patients. Further advances in the development of effective MM therapeutic agents in both ASCT and non-ASCT populations and patient access to them is needed to improve outcomes.

HLA-mismatched micro-transplantation as post-remission treatment compared to autologous hematopoietic stem cell transplantation or consolidation with single agent cytarabine for favorable-or intermediate-risk acute myeloid leukemia

ABSTRACTObjectivesOptimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML.MethodsWe retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021.ResultsThe neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years.ConclusionMST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years.

Analysis of Positive Results of 18F-FDG PET/CT Imaging after Hematopoietic Stem Cell Transplantation in Lymphoma.

The purpose of this study was to differentiate between false-positive and true-positive positron emission tomography (PET) results after hematopoietic stem cell transplantation (SCT) for lymphoma involvement by analyzing several clinical variables and specific imaging features. Patients with lymphoma who received SCT and underwent post-transplantation 18F-FDG PET/CT scans between January 2013 and April 2021 at our institution were included. Associations between PET positivity and related clinical information were assessed using t-tests and χ2 tests. The significance of variables differentiating benign lesions from malignant FDG-avid lesions was evaluated by logistic regression analysis. Survival probabilities were derived from Kaplan-Meier curves and compared using the log-rank test. A total of 185 patients (235 post-transplantation PET/CT scans) were enrolled in our present study. Compared with those with true-positive PET results, patients with false-positive PET results exhibited a better prognosis. For the autologous SCT group, false-positive cases were more commonly seen when FDG-avid foci appeared outside the sites of the original disease (p = 0.004), and the integrated CT imaging showed negative results (p = 0.000). In multivariate logistic regression analysis, integrated CT results were the only significant factor. For the allogeneic SCT group, false-positive cases were significantly more commonly seen when DS = 4 (p = 0.046), FDG-avid foci appeared outside the sites of the original disease (p = 0.022), and the integrated CT imaging showed negative results (p = 0.001). In a multivariate logistic regression analysis, whether FDG-avid foci were in the sites of the original disease and integrated CT results were both significant factors. False-positive FDG uptake in post-transplantation PET was not uncommon. Several variables could provide an important reference to differentiate false-positive from true-positive post-SCT PET results for lymphoma involvement. ChiCTR2300067355.

CLINICAL EFFICACY OF CD34 POSITIVE SELECTION EX‐VIVO PURGING DURING AUTOLOGOUS STEM CELL TRANSPLANTATION IN PERIPHERAL T CELL LYMPHOMA

Background: Autologous stem cell transplantation (ASCT) is the standard treatment for peripheral T-cell lymphomas (PTCLs). Strategies that reduce the relapse rate and treatment-related mortality are essential for successful ASCT. Because in vivo/in vitro purging methods using rituximab are not appropriate for T-cell lymphomas, an ex vivo CD34+ selective purging system using CliniMACS is the most reliable method to reduce autograft tumor cell contamination in these tumors. In the present study, we retrospectively analyzed the clinical outcomes of HDT/ASCT after ex vivo purging via the CD34+ selective method in T-cell NHL patients. Methods: We retrospectively investigated the influence of ex vivo purging with CD34+ selection to maximize the effects of ASCT. Of 67 consecutive PTCL patients, 32 and 35 underwent purged and unpurged ASCT. Results: The purged group had improved overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (hazard ratio [HR] = 2.68, p = 0.016; HR = 3.97, p = 0.002; and HR = 3.65, p = 0.004, respectively), compared to the unpurged group. Prognostic factor analysis showed that unpurged ASCT, chromosomal abnormalities at initial diagnosis, high risk, and pre-ASCT disease status were associated with poor survival outcomes. Subgroup analysis demonstrated that purging was most appropriate for International Prognostic Index high-risk patients who underwent upfront ASCT (HR = 3.35 [OS] and = 6.59 [DFS]). In purged ASCT group, NK cell activity and the lymphocyte-to-monocyte ratio known as an independent prognostic factor were increased after ASCT with statistical significance; the lymphocyte-to-monocyte ratio (LMR) was significantly increased after ASCT in the purged group (mean difference = 1.484, 95% CI = 0.407–2.560; p = 0.009). Also, Engraftment was achieved in all patients with no need for unpurged autologous stem cell backup in purged group. There were no engraftment failures or differences in adverse events including of transplant-related viral infections between the two groups. The research was funded by: The research was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2020R1G1A1099654). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Stem Cell Transplant No conflicts of interests pertinent to the abstract.

Single or tandem autologous stem cell transplantation for treating Chinese patients with refractory/relapsed classical Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) is the standard treatment strategy for refractory or relapsed classical Hodgkin lymphoma (R/R cHL). However, a single transplantation is insufficient to cure the disease because of unfavorable risk factors. Herein, we evaluated the outcomes of single or tandem ASCT in patients with R/R cHL, especially in high-risk patients. We retrospectively analyzed R/R cHL patients who underwent single or tandem ASCT between April 2000 and June 2021 at the Beijing Cancer Hospital and Peking University International Hospital. A total of 134 patients were enrolled. Patients were allocated to a favorable-risk group (group A, n = 33), an unfavorable-risk group (group B, n = 81) that underwent single ASCT, and an unfavorable-risk group that underwent tandem ASCT (group C, n = 20). The median follow-up time was 99 months (range, 91-107 months), and no treatment-related deaths occurred after single or tandem ASCT. However, 27 patients (2 in group C) died during the follow-up period. The groups A, B, and C had 5-year progression-free survival (PFS) rates of 77.05%, 45%, and 74.67%, respectively (p = 0.0014), and 5-year overall survival (OS) rates of 89.85%, 76.06%, and 95%, respectively (p = 0.18). Neither the median PFS rates of groups A and C nor the OS rates of all groups were reached. Our study discusses the advantages of tandem transplantation for high-risk patients with R/R cHL.

Clinical significance of high-dose chemotherapy with autologous stem cell transplantation in the era of novel agents in patients older than 65 years with multiple myeloma

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard treatment for symptomatic multiple myeloma (MM) in patients under 65 years of age. However, the performing of ASCT in older patients > 65 years without comorbidities or complications is controversial. Introduction of novel drugs, such as daratumumab, has improved the long-term survival of patients with MM who are ineligible for ASCT. This retrospective study aimed to evaluate the clinical significance of ASCT in older patients, even in the era of novel drugs. A total of 55 patients aged 65–74 years (15 ASCT recipients and 40 ASCT-ineligible patients) newly diagnosed with MM between March 2013 and October 2021 at our institution were analyzed in this study. There were no significant differences in the 3-year overall survival (84.6% vs. 90.6%, p = 0.72) and progression-free survival (PFS) (61.2% vs. 75.1%, p = 0.40) between ASCT recipients and ASCT-ineligible patients. There was also no significant difference in complete response (CR) with minimal residual disease (MRD)-negative rate between the two groups (27% vs. 33%, p = 1.0). Multivariate analysis showed that CR was an independent predictor of PFS (hazard ratio [HR], 0.26; 95% confidence interval, 0.08–0.76; p = 0.01). In this retrospective study, despite patients who were determined to be intolerant to ASCT, the non-ASCT group was non-inferior to the ASCT group in PFS and overall response rate. The results of this study confirm that the significance of ASCT is diminishing in patients 65 years of age and older because newer agents can achieve good responses without ASCT.

Daratumumab, pomalidomide, and dexamethasone (DPd) followed by high dose chemotherapy-Autologous Stem Cell Transplantation leads to superior outcomes when compared to DPd-alone for patients with Relapsed Refractory Multiple Myeloma

Background and objectivesWhile the role of autologous stem cell transplant (ASCT) in the first line therapy for newly diagnosed multiple myeloma is well established, efficacy of ASCT for patients with relapsed refractory multiple myeloma (RRMM) in the era of novel therapeutic agents remains unknown. In this single center retrospective analysis, we evaluated and compared the efficacy and safety outcomes of patients with RRMM treated with daratumumab pomalidomide dexamethasone (DPd) alone versus (vs) DPd followed by ASCT. MethodsA total of 83 patients with RRMM who were treated with and achieved at least partial response (PR) with DPd were evaluated by electronic medical records. All patients who responded to DPd and were deemed eligible for ASCT proceeded with high dose melphalan followed by autologous stem cell infusion (DPd + ASCT group). Remaining patients continued DPd until disease progression or intolerable toxicities (DPd-alone group). Responses were evaluated using the International Myeloma Working Group response criteria and toxicities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events. Patient and disease characteristics, as well as efficacy and safety outcomes were summarized using descriptive statistics. Kaplan-Meier analyses were used to estimate progression-free survival (PFS) and overall survival (OS). ResultsA total of 21/83 (25%) patients with RRMM who achieved at least PR to DPd underwent ASCT (DPd + ASCT group) while the remaining 62/83 (75%) continued DPd without ASCT (DPd-alone group). For the entire patient population, median age was 66 years (42-81), 49 (59%) patients were male, 54 (65%) patients had IgG isotype, 21 (25%) patients had R-ISS stage III disease, 51 (61%) patients had high-risk cytogenetics, and 17 (20%) patients had extramedullary disease. Patient age, disease stage, cytogenetic risk profile were well balanced between two groups. A stringent complete response was seen in 10 (16%) and 12 (57%) patients in the DPd-alone and DPd + AST groups, respectively. Median PFS was 17.5 months in the DPd-alone vs 42.2 months (p=0.006) in the DPd + ASCT group. Median OS was 38.1 months in the DPd-alone group vs not reached in the DPD + ASCT group (p=0.009). The most common grade 3 or 4 treatment-related adverse events (TRAE) were myelosuppression and gastrointestinal toxicities, more commonly seen in the DPd + ASCT group. No treatment-related mortalities were observed in either group. ConclusionPatients with RRMM who responded to DPd and underwent HDT-ASCT demonstrated superior depth and duration of remission compared to those who received DPd-alone. Although DPd followed by ASCT is associated with more cytopenias and gastrointestinal toxicities, this treatment appears to be overall safe for patients with RRMM.

The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma.

The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively (P < 0.01). The median progression-free survival was 16.3 (2.6-24.5) months, and the median overall survival was 19.3 (6-24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS (P < 0.01) and OS (P < 0.01). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) and cytokine release syndrome (≥grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.

Effect of autologous hematopoietic stem cell transplantation for patients with peripheral T-cell lymphoma in China: A propensity score-matched analysis.

The role of consolidation therapy with autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL) in first complete remission (CR1) or partial remission (PR1) remains controversial. The existing data from China are limited. Therefore, we aimed to investigate the effect of ASCT on the survival of Chinese patients with PTCL showing response to induction chemotherapy at our hospital. We retrospectively reviewed the data of patients with PTCL (excluding Natural killer/T cell lymphoma) in CR1 or PR1 treated at Peking University Hospital &Institute from 1996 to 2020. Propensity score matching (PSM) was used to balance clinical characteristics between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Of the 414 selected patients, 73 received ASCT consolidation and 341 did not. Over a median follow-up of 5.7 years, survival was significantly better in the ASCT group than in the non-ASCT group (median EFS, 8.1 years vs. 2.8 years, P = 0.002; median OS, 14.9 years vs. 10.2 years, P = 0.007). The 5-year EFS and OS rates were 68.4% and 77.0% in ASCT group, and 43.2% and 57.6% in non-ASCT group, respectively. The survival benefit was confirmed in the propensity score matched cohort (46 patients who received ASCT and 84 patients who did not receive ASCT): P = 0.007 for median EFS and P = 0.022 for the median OS. Cox regression analysis showed that ASCT was independently associated with better survival: hazard ratio (HR) for EFS, 0.46 (95% CI: 0.28-0.76); HR for OS, 0.50 (95% CI: 0.31-0.84). Subgroup analysis showed that ASCT was more likely to benefit higher-risk patients and those with advanced disease. Among the subtypes of PTCL, the benefit was significant in angioimmunoblastic T-cell lymphoma (HR = 0.26 [95% CI: 0.10-0.66] for EFS and 0.29 [95% CI: 0.12-0.74] for OS), but not in the other subtypes. ASCT may improve the long-term survival of patients with PTCL in first CR or PR, especially for patients with angioimmunoblastic T-cell lymphoma. The specific groups most likely to benefit from upfront ASCT need to be clearly identified.

Limited Long-Term Benefit of Upfront Autologous Stem Cell Transplant on Survival in Severe Renal Impairment in Multiple Myeloma in Novel Drug Era, a Retrospective Multi-Center Study in China

Background Renal impairment (RI) is a common complication of multiple myeloma (MM) affecting approximately 20%-30% of the patients at diagnosis. The presence of severe RI is associated with an increased risk of early death and poor prognosis in myeloma. The impact of autologous stem cell transplant (ASCT) on outcome in severe RI patients remains controversial. Therefore, we performed a retrospective real-world analysis to clarify the effect of ASCT on the survival of MM patients with severe RI. Methods Clinical data of 337 MM patients with severe RI at diagnosis were collected from three centers in China from April 2004 to January 2020. Severe RI was defined as an increase creatinine ＞177 umol/L (or 2mg/L) or an estimated glomerular filtration rate ≤40 ml/min/1.73 m2 using the simplified modification of diet in renal disease (MDRD) formula. RI caused by other confirmed pathological diagnosis except for tubular nephropathy was excluded. We excluded patients underwent salvage ASCT (6 cases), patients older than 65 years (107 cases), and traditional introduction therapy (2 cases). At last, there were 232 cases for analysis, containing 59 cases received ASCT. All enrolled patients were treated with novel-agent introduction. Patients were divided into the ASCT group and the non-ASCT group. Hematological and renal response were assessed based on the International Myeloma Working Group (IMWG) criteria. Results The median age for all patients at diagnosis was 55 years old (range: 37-65 years old). 37% presented with free light chain myeloma. There were 4 patients underwent double-ASCT in the ASCT group. All dialysis patients in ASCT group were off dialysis after induction therapy. Baseline profiles between ASCT and non-ASCT group were matched in sex, M-protein isotype, ISS stage, and induction therapy. More patients were on dialysis at diagnosis in non-ASCT group (34.7% vs 19.3%, P=0.04). There were 59/159 patients presented unfavorable cytogenetic abnormality (del(17p), t(4;14), t(14;16)), including 40 cases (34.2%) in non-ASCT group and 19 cases (41.3%) in ASCT group (P=0.47). The 1q amplification presented 21.4% in non-ASCT group and 22.2% in ASCT group (P=0.56). In terms of hematological response, at least VGPR accounts for 88.1% in the ASCT group and 50.3% in the non-ASCT group (P<0.001). The overall renal response was significantly higher in the ASCT group than that in the non-ASCT group (94.9% vs 54.3%, P<0.001). There was the similar tendency for at least renal PR between ASCT and non-ASCT groups (88.1% vs 41.3%, P<0.001). The transplant-related mortality (within 3 months after ASCT) was 6.8%. Early mortality within 1 year was 6.7% in the ASCT group and 19.8% in the non-ASCT group (P=0.002). The median follow-up for all patients was 37.6 months (range: 1-157 months) and the median overall survival (OS) was 49.5 months (95% CI：42-57 months). In the ASCT group, the median OS was much longer than ASCT group (57.3 months vs 42.8 months, P =0.052). But there was no difference in PFS between the two groups (36.9 months vs 26.5 , p=0.348). As the log-rank test didn't hold the proportional hazards assumption, it would have low power. We use the two-stage landmark analysis to further determine the effect of ASCT on survival. In landmark analysis, 3-year PFS rate in ASCT group was significantly higher (54.0% vs 41.9%, P=0.024). Within 5-year follow-up, OS was significantly longer in the ASCT group than that in non-ASCT group (OR=0.61, 95%CI: 0.39-0.97, P=0.04). Beyond the 5-year time point, OS was similar between the two groups (OR=1.59, 95%CI: 0.60-4.20, P=0.35). In univariate analysis, at least renal MR, at least hematological VGPR, PLT＞100×109/L, and BMPC ≥60% were correlated with longer OS. In multivariate analysis, at least renal MR (HR=0.61, 95%CI: 0.39-0.96, P=0.031), at least hematological VGPR (HR=0.41, 95%CI: 0.27-0.63, P<0.001), and PLT＞100×109/L (HR=0.43, 95%CI: 0.28-0.66, P<0.001) were independent predictor of OS. Although upfront ASCT could remarkably prolong OS in severe RI myeloma, it was not confirmed in multivariate analysis. Conclusions In the novel agent era, role of upfront ASCT in myeloma with severe RI remains uncertain. In our analysis, it seems the benefit of the OS from novel-drug induction and upfront ASCT was observed in the first 5-year, but the long-term survival benefit was limited. Instead, deep hematological response and renal recovery was strong predictors for OS.

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

High-Dose Idarubicin Plus Busulfan As Conditioning Regimen to Autologous Stem Cell Transplantation Improves Prognosis in Patients with Favorable and Intermediate-Risk AML

Introduction: The optimal post-remission therapy (PRT) for patients with favorable and intermediate-risk acute myeloid leukemia (AML) remains uncertain. We retrospectively analyzed and compared the efficacy of high-dose idarubicin plus busulfan conditioning regimen combined with autologous stem cell transplantation (ASCT) and intermediate- to high-dose cytarabine consolidation chemotherapy for post-remission treatment (PRT) in patients with favorable- and intermediate-risk AML. Methods: A total of 116 patients with favorable- and intermediate-risk AML according to 2022 ELN risk stratification who were treated with ASCT (n=58) or intermediate- to high-dose cytarabine regimen (n=58) were enrolled in this study. All the patients received IA regimen (idarubicin 10-12 mg/m2 on days 1 to 3 and cytarabine 100 mg/m2/d on days 1 to 7) as induction and complete remission (CR) was obtained in all the patients after one course of induction. Fifty-eight patients were subjected to 2-4 courses of intermediate- to high-dose cytarabine (cytarabine 2-3 g/m2 twice daily on days 1-3). High-dose idarubicin plus busulfan conditioning regimen (I-Bu; idarubicin 20 mg/m2 continuous i.v. from days -13 to -11, busulfan in intravenous formulation: 3.2 mg/m2 or oral formulation: 4.0 mg/m2 from day -5 to -2) combined with ASCT was given to the other 58 patients 2-3 courses of intermediate- to high-dose cytarabine and mobilization and collection of peripheral blood stem cells. Clinical outcomes were retrospectively analyzed for patients belonging to the two treatment arms. Results: The median age was 38 (14-60 years) and 32 years (14-59 years) in ASCT and chemotherapy cohort, respectively. After a median follow-up of 68 months (1-200 months), and the median overall survival (OS) has not been reached in both groups. The 5-year and 10-year OS in the ASCT group was 77.5% and 71.5%, and 5-year and 10-year disease-free survival (DFS) was 73.9% and 71.1%, respectively. The 5-year OS and DFS in the chemotherapy group were 53.5% and 52.4%, respectively. The median OS and DFS of the patients in ASCT group were significantly better than those in chemotherapy group (OS: p=0.009, HR=0.444, CI 0.237 to 0.831; DFS：p=0.018, HR=0.494,CI 0.268 to 0.911). No treatment-related early death (death within 8 weeks after treatment) was observed in the ASCT group. All the patients experienced severe bone marrow suppression and severe (grade 3 or 4) hematological toxicity, and we did not observe severe (grade 3 or 4) cardiotoxic complications during or after ASCT in all the patients. Conclusions: ASCT with I-Bu regimen is possibly a promising PRT for patients with favorable- and intermediate-risk AML in the first CR, improving prognosis of these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Autologous Versus Haploidentical Stem Cell Transplantation in Adult Patients with Intermediate Risk Actue Myelogenous Leukemia in First Complete Remission and Undetectable Minimal Residual Disease: A Global Preliminary Analysis of Chinese Data

Background: Stem cell transplantation (SCT) is a potentially curative post-remission therapy for intermediate-risk acute myeloid leukemia (AML) patients. For patients in first remission (CR1) with negative measurable residual disease (MRD) and without a HLA-matched donor, both autologous SCT (ASCT) and haploidentical donor SCT (haplo-SCT) were acceptable options, but it is controversial that which one is preferred. Methods: A retrospective study was conducted in 8 Chinese centers. The inclusion criteria were: 1) adult patients >18 years old; 2) diagnosis as AML with intermediate-risk according to ELN 2017; 3) ASCT or haplo-SCT underwent between 2010-2019; 4) in CR1 and MRD negative before transplant. The Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), cumulative incidence of relapse (CIR), treatment-related mortality (TRM), and graft-versus-host disease-free and relapse-free survival (GRFS). Results: Totally 299 patients were enrolled in this study, including 97 recepients after ASCT and 202 recipients after haplo-SCT (Table 1). The median follow-up was 28 months in ASCT group versus 35 months in haplo-SCT group. Compared to haplo-SCT, patients after ASCT had increased 3-year CIR (27.0% ± 0.2% versus 13.5% ± 0.1%, p = 0.004) but reduced 3-year TRM (3.5% ± 0.0% versus 12.0% ± 0.0%, p = 0.013), which led to similar 3-year OS (80.8% ± 4.3% versus 79.2% ± 3.1%, p = 0.796) and PFS (69.5% ± 5.0% versus 73.7% ± 3.3%, p = 0.504). Moreover, the 3-year GRFS was remarkable better in ASCT group (69.5% ± 5.0% versus 55.9% ± 3.6%, p = 0.009) (Figure 1), which implied a survival with superior quality of life (QoL). In multivariate analysis, haplo-SCT independently related to an improved CIR, while increased TRM and reduced GRFS. Additionally, age more than 50 was associated with the worse OS, CIR and GRFS. Conclusions: We concluded that both ASCT and haplo-SCT were applicable for patients with intermediate-risk AML in MRD-negative CR1, but the absence of GVHD might potentially favor the QoL for patients receiving ASCT. Randomized trials are needed to confirm our conclusion. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Consolidative Autologous Stem Cell Transplantation Versus Whole Brain Radiation in PCNSL; a Nationwide Analysis.

The best consolidation strategy after induction chemotherapy in Primary CNS Lymphoma (PCNSL) remains controversial. Our objective is to estimate the overall survival (OS) for autologous stem cell transplantation (ASCT) versus whole brain radiation (WBRT) in the consolidation setting. We also sought to evaluate the factors affecting treatment selection METHODS: We identified 1620 patients with PCNSL who received chemotherapy followed by either ASCT or WBRT between 2004 and 2015 from the National Cancer Database. A propensity score weighting methodology was used to compare survival outcomes. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of ASCT use. Only 12.2% of patients received ASCT, and this proportion rose steadily between 2004 and 2015, with APC of +23%. Treatment selection was affected by age, type of area, distance from the treating facility, and level of education. With a median follow-up of 68.4 months, adjusted-median OS was 91.4 months and not reached for WBRT and ASCT groups, respectively (P < .001). 5-year OS was 74.4% in the ASCT group versus 58.7% in the WBRT group (HR 0.40, 95% CI 0.27-0.60, P -value < .01). Socioeconomic factors affect the selection of consolidative treatment in patients with PCNSL which can alter outcomes. Frequency of consolidative ASCT is increasing for patients with PCNSL. This is the first and largest cohort study, to our knowledge, to show an OS advantage in favor of ASCT. This OS benefit needs to be confirmed in a randomized controlled fashion.

Vincristine, Doxorubicin, and Dexamethasone Induction before Autologous Stem Cell Transplantation in Patients with AL Amyloidosis: A Retrospective Comparison with Frontline Stem Cell Transplantation.

Objective High-dose melphalan and autologous stem cell transplantation (ASCT) therapy for AL amyloidosis are now associated with reduced mortality based on the application of strict criteria. However, there is no long-term evidence concerning the performance of induction therapy with newer agents, such as bortezomib or daratumumab. Concerns regarding long-term relapse despite treatment with ASCT exist, and missing the opportunity to perform ASCT might occur if induction proves to not be efficacious and cardiac amyloidosis progression deprives the patients of a chance to receive ASCT. We herein report good amyloid control by vincristine, doxorubicin, and dexamethasone (VAD) induction therapy and argue the importance of induction therapy before ASCT. Methods We compared patients who underwent VAD induction and ASCT (VAD+ASCT) with patients who underwent frontline ASCT in our hospital. Patients A total of 26 patients with histologically proven AL amyloidosis were included (18 in the VAD+ASCT group and 8 in the frontline ASCT). Results In the VAD+ASCT group, the 10-year overall survival and renal response rates were 82% and 43%, respectively. The renal response rate at two years in the VAD+ASCT group was significantly better than that in the frontline ASCT group. Although there was no significant difference in the survival rates between the two groups, the time to next treatment or death was significantly better in the VAD+ASCT group than in the the frontline ASCT group. Acute kidney injury was the most frequent reason for failure to receive two courses of VAD, and early mortality was mainly due to gastrointestinal complications. Conclusion Considering that only those who underwent 2 courses of VAD experienced a 10-year renal response, induction therapy was deemed to be directly related to the long-term control of AL amyloidosis.

Brentuximab Vedotin versus checkpoint inhibitors: Which one? When? Why should be preferred?

About 15% of classical Hodgkin lymphoma (cHL) patients remain refractory to first-line therapy and about one third of the responding patients relapse1. The standard of care for relapsed or refractory (R/R) cHL is salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT)2. Three novel agents effective in R/R cHL were introduced; brentuximab-vedotin (BV), anti-CD30 antibody-drug conjugate3 and the programmed-death-1 (PD-1) blocking antibodies, nivolumab and pembrolizumab4, 5 has been approved. The optimal line to incorporate these agents is an actual dilemma. BV and PD1-blockers are effective in R/R cHL after ASCT. KEYNOTE-204 study reported that pembrolizumab treatment was associated with significantly longer PFS compared with BV (median:13.2 vs 8.3 months)6. In case of durable responses with PD1-blockers, cessation of the treatment may be an individualized decision and high response rates to re-treatment with PD1-blockers is an important advantage7. There is not obvious differences in the efficacy and toxicity of nivolumab and pembrolizumab8. We can conclude that PD1-blockers could be preferred over BV in patients who relapse following ASCT and who are naïve to BV and PD-1 blockade. For patients relapsing after ASCT with prior BV or PD1-blocker exposure, selection of the agent that has not been used previously could be recommended8. BV and PD1-blockers are incorporated into the pre-ASCT salvage regimens in clinical trials. In the phase II BRaVE study, BV added to DHAP provided a complete metabolic response rate of 81% before ASCT, with a 2-year PFS and OS rates of 74% and 95%, respectively9. Similarly, pembrolizumab in combination with GVD provided an overall response rate (ORR) of 100%10. BV and nivolumab combination resulted in an ORR of 85%. The 3-year PFS rate for ASCT group was 91%11. Regarding these data, the need for ASCT will be an important point of debate in the next years. In case of primary refractory disease, chemotherapy-based salvage regimens remain the standard. Combination treatment with BV and nivolumab resulted in a 21-month PFS of 65% in this group11, which may be a satisfactory option in the future. Post-ASCT consolidation with BV is now standard of care in patients with risk factors defined by AETHERA trial12, which is supported by real-world data including pre-treated with and responsive to BV patients13. Novel agents are not recommended in the front-line management of early-stage disease. ECHELON-1 study performed on treatment-naïve stage III/IV cHL patients reported 6-year PFS, and OS ratio were 82.3% and 93.9% for BV-AVD cohort versus 74.5% and 89.4% for ABVD cohort14. Beside advanced stage cases, BV-based therapies should be considered for elderly, unfit patients who cannot tolerate combination chemotherapies, as they are associated with longer duration of response compared to BV monotherapy8. Giving decision about novel therapies, major adverse events, such as neuropathy for BV and immune related events for PD1-blockers. Optimal timing of BV and PD1-blockers and treatment strategies in case of resistance to novel agents are critical questions for the future of cHL management, which hopefully will be answered by the results of clinical trials and real-world data.

Real-world treatment patterns for patients with newly diagnosed multiple myeloma in Alberta, Canada

The purpose of this study is to describe the real-world multiple myeloma (MM) population in Alberta by examining patient/clinical characteristics and the treatment landscape. A retrospective, observational study was conducted using province-wide, administrative health data from Alberta, Canada evaluating newly diagnosed MM (NDMM) patients. Between 1 April 2011 and 31 March 2017, 1377 treated NDMM cases were identified. Of those, 328 (23.8%) received an autologous stem cell transplant (ASCT) within the first year of diagnosis. In the ASCT group, 189 advanced to second-line (57.6%), 103 (32.6%) to third-line and 97 (29.5%) had four or more lines of therapy. In non-ASCT patients, 553 (52.7%) advanced to second-line, 238 (22.7%) to third-line, and 154 (14.7%) had 4 or more lines of therapy. We observed a significant treatment attrition rate in NDMM. Therefore, the use of best therapy upfront and novel strategies aiming to decrease attrition rates in MM is encouraged.

P978: IXAZOMIB VERSUS LENALIDOMIDE OR IXAZOMIB AND LENALIDOMIDE COMBINATION AS MAINTENANCE REGIMEN FOR PATIENTS WITH MULTIPLE MYELOMA: INTERIM ANALYSIS OF A MULTI-CENTER PROSPECTIVE STUDY IN CHINA

Background: Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2nd generation oral proteasome inhibitor (PI), has been approved for MT because of its convenience and tolerability. Aims: We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimen in NDMM patients. Methods: This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry since September 2019. After 4 cycles of front-line induction therapy, patients reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start maintenance therapy. Patients did not reach PR would switch to 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1–21 of 28day cycles. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was PFS from MT. Results: A total of 176 patients were enrolled, including 58 in I-MT, 72 in L-MT and 46 in IL-MT. The demographic and clinical characteristics, including gender ratio, age, paraprotein isotype, ISS, R-ISS, were comparable among different MT regimen groups either receiving ASCT or not at baseline (Table 1). The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were lower in L-MT without ASCT and I-MT with ASCT. The median follow-up duration since MT was 10.6, 12.6 and 11.1 months in I-MT, L-MT and IL-MT groups in non-ASCT patients, while 9.3, 14.0 and 12.2 months in ASCT patients, respectively. In non-ASCT groups, the disease progression rates were 13.5%, 10.2% and 10.8%, whereas 0, 21.7% and 0 in ASCT groups. The median PFS and OS were not reached (NR) in all groups. There were 73.1%, 73.4% and 78.3% of the patients reached VGPR or better before MT in non-ASCT patients, while the rates improved to 80.8%, 81.6% and 86.5% during follow-up. The depth of response did not change in ASCT patients. In the whole cohort, the prevalence of peripheral neuropathy (PN) was 18.9% on I-MT, 8.3% on L-MT and 21.7% on IL-MT. Grade 2 PN occurred in 3, 0 and 2 patients, respectively. The incidence of gastrointestinal (GI) events was 12.1%, 1.4% and 15.2%, respectively. Grade 3 GI events occurred in 3, 0 and 1 patients. The incidence of grade 3-4 hematologic toxicities was 1.7%, 4.2%, and 2.2%. Infections developed in 10.3%, 2.8% and 4.3% patients. No drug withdrawal was related to adverse events. Image:Summary/Conclusion: Due to inadequate access to melphalan and low rate of ASCT, the PFS of NDMM in Chinese patients was relatively inferior. We design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint--PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable.