Time Of Autologous Stem Cell Transplantation Research Articles

Autologous Stem Cell Transplant in Fit Patients With Late Relapsed Diffuse Large B-Cell Lymphoma That Responded to Salvage Chemotherapy

The standard of care (SOC) for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) ≥12 months after completing frontline therapy is salvage chemotherapy (ST) followed by autologous stem cell transplant (ASCT). However, this strategy may not be optimal for patients with certain clinical characteristics. We retrospectively studied 151 patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent ST and ASCT at Mayo Clinic between July 2000 and December 2017 or the University of Iowa between April 2003 and April 2020. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using the Kaplan–Meier method. The median time from frontline therapy completion to 1st relapse was 26.9 months. The median line of ST was 1 (range 1–3), and 17 (11%) patients required >1 line of ST. Best response before ASCT was partial response (PR) in 60 (40%) and complete response (CR) in 91 (60%) patients. The median age at ASCT was 64 yr (range 19–78), and 36 (24%) patients were of ≥70 yr. The median follow-up after ASCT was 87.3 months. The median PFS and OS were 54.5 and 88.9 months, respectively. There was no significant difference in PFS and OS based on the age at ASCT (including patients aged ≥70–78 yr), sex, transplant era, time to relapse, LDH, extranodal site involvement, and central nervous system/nerve involvement at relapse. However, patients with advanced-stage relapse had inferior PFS than those with early-stage relapse (median 45.3 versus 124.7 months, P = .045). Patients who required > 1 line of ST, compared to those requiring 1 line, had significantly inferior PFS (median 6.1 versus 61.4 months, P < .0001) and OS (17.8 versus 111.7 months, P = .0004). There was no statistically significant difference in survival in patients who achieved PR versus CR, though numerically inferior in the former, with median PFS of 38.9 versus 59.3 months (P = .23) and median OS of 78.3 versus 111.7 months (P = .62). Patients achieving CR after 1 line of ST had excellent post-ASCT outcomes, with median PFS of 63.7 months. In conclusion, survival after ASCT was unfavorable in patients with late relapsed DLBCL (≥12 months) who required more than 1 line of ST to achieve PR or CR, and such patients should be treated with alternative therapies. Conversely, survival was favorable in patients who required only 1 line of ST, supporting the current clinical practice of ASCT consolidation in these patients. Moreover, outcomes were favorable in patients aged ≥70 to 78 yr at ASCT, similar to younger patients, highlighting the safety and feasibility of this approach in such patients.

Identification of Clinical-Biological Features of Newly Diagnosed Early Relapse Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation

Despite many therapeutics advances, Multiple Myeloma (MM) remains an incurable hematological malignancy with a cohort of patients who relapse early or does not respond to first-line therapy, including autologous stem cell transplantation (ASCT). The proportion of patients with early relapse is stable over time at about 30% and they have a median Overall Survival (OS) less than 3 years. Consequently, clinical and/or biological features that identify patient at high risk for early relapse at diagnosis represent a critical unmet medical need. With the aim of identify possible factors of early relapse (ER), we conducted a retrospective, observational, single center study on a cohort of 74 MM patients who received an upfront ASCT between 2011 and 2021 after a novel agent-based induction at the Hematological and BMT Unit of the University Hospital of Parma (Italy). The primary end point of the study was the assessment of possible predictive markers for ER, defined as progressive disease that occurred within 18 months from the time of ASCT. Clinical, biochemical and cytogenetics features of the cohort of MM patients were evaluated (Table 1). Definitions of response and progression were used according to the International Myeloma Working Group (IMWG) response criteria. All statistical analyses were done by SPSS Statistics. The characteristics of cohorts were summarized using the median value for continuous variates and the frequency for categorical ones. The Pearson chi-square test and Student t-test were used to identify differences between groups for categorical and continuous variables, respectively. Kaplan-Meier Curve with log-rank test were used to analyze survival data. The bivariate logistic analysis was conducted to recognize independent factors predicting ER, subsequently Cox regression analysis was performed to confirm the validity of multivariate analysis for survival data. The cohort characteristics were summarized in table 1. Among the 74 MM patients included in the study, a total of 19 patients (25.5) experienced ER, with mean time to relapse of 15.6 (18.0) months. Univariate statistical analysis identified as possible predictive markers for early relapse at diagnosis: IgA MM (p &amp;lt; 0.05), elevated serum LDH level (p &amp;lt; 0.05), C-CRAB criteria (p &amp;lt; 0.05), high risk cytogenetic aberrations (p &amp;lt; 0.05), stage R-ISS III (p &amp;lt; 0.001) and stage R2-ISS III or IV (p &amp;lt; 0.001). Multivariate statistical analysis confirmed IgA isotype (p &amp;lt; 0.05) and higher stage according to R2-ISS (p &amp;lt; 0.001) as effectively independent predictive risk factors for ER. Time-to-event analysis displayed a mean progression free survival (PFS) from transplant of 24.7 (16.0) months and 32.5 (19.0) months for those with IgA MM and stage R2-ISS III or IV, respectively. In the group of patients with IgA isotype the mean OS from transplant was 49.5 (30.0) months, while the mean OS from diagnosis was 58.0 (35.0) months without statistically significant differences compared to counterpart. In the group of patients with stage R2-ISS III or IV the mean OS from transplant was 48.2 (41.0) months, while the mean OS from diagnosis was 56.5 (49.0) months. Finally, in ER cohort the mean OS from diagnosis was 47.1 (35.0) in comparison with the 75.0 (71.0) months of non-ER cohort. In conclusion, this retrospective study was able to identify the main features of newly diagnosed early relapsed MM patients eligible to ASCT identifying the IgA isotype and the R2-ISS score system as the main predictive prognostic factors for early relapse in this cohort of patients.

Improving the Utilization and Tolerability of Thiotepa-Based Autologous Stem Cell Transplantation in Primary CNS Lymphoma

Background: Thiotepa-based autologous stem cell transplantation (ASCT) improves survival in primary central nervous system lymphoma (PCNSL) but up to 30-60% of patients are unable to receive ASCT after MATRix induction, frequently due to treatment-related adverse events. Common conditioning regimens such as thiotepa/BCNU or thiotepa/busulfan/cyclophosphamide have also been associated with risks of pulmonary toxicity or increased transplant-related mortality. Novel strategies to improve the utilization and tolerability of ASCT are therefore needed to maximize the curative potential of this therapy in PCNSL. Methods: This retrospective population-based study included all patients diagnosed with large B-cell lymphoma-type PCNSL who were intended for ASCT in the province of Alberta, Canada between 2011 and 2022. Provincial treatment guidelines recommended an abbreviated, low-intensity induction protocol to reduce toxicity and increase transplantation rates (Figure 1B). Step 1 included 2 cycles of rituximab/high-dose methotrexate (HD-MTX). Step 2 involved 1 cycle of rituximab/high-dose cytarabine (HDAC) for peripheral blood stem cell mobilization. Step 3 consisted of 2 cycles of rituximab/HD-MTX/HDAC and was made optional in July 2018 so that patients with sufficient disease response and performance status following Step 2 could proceed immediately to ASCT. Conditioning consisted of thiotepa 300 mg/m 2 ×2 days and busulfan 3.2mg/kg ×3 days (TT/Bu). Dose reductions of TT/Bu by 10% for every 5 years over the age of 60 were recommended as of May 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and compared between groups using the log-rank test. Results: The intention-to-transplant (ITT) cohort included 71 patients with median age 58 years (range 26-72), representing 81% of patients aged 18-60 and 55% of those aged 61-72 who were diagnosed with PCNSL in Alberta during the study period. The proportion of patients aged 61-72 who were treated with ITT increased from 42% before 2018 to 70% afterwards. Fifty-six (79%) ITT patients proceeded to ASCT while 15 (21%) did not due to poor performance status (n=6), treatment-related adverse events (n=5), or disease progression (n=4). There was 1 (1%) death due to infection-related non-relapse mortality (NRM) during induction. The routine omission of Step 3 starting in 2018 resulted in high transplantation rates at 29/35 (83%) compared to 27/36 (75%) in the preceding era. With median follow-up time 3.9 years, the 4-year PFS was 69% (95% CI 56-79%) and OS was 80% (95% CI 67-88%) in the ITT cohort (Figure 1A). For the 56 patients who received ASCT, 4-year PFS was 75% (95% CI 57-86%) and OS was 85% (95% CI 68-93%) from the time of ASCT. There was no significant difference in PFS between patients in complete response (CR)/unconfirmed CR versus partial response (PR) before ASCT (p=0.86); however, 5 patients with progressive disease before ASCT had inferior PFS compared to those with CR/CRu/PR (4-year PFS 40% vs 82%, p=0.0002). Relapse occurred in 8 (14%) patients at median 373 days (range 54-1411) after ASCT, including 7 with CNS relapse and 1 with systemic relapse. No patient in remission after ASCT received whole brain radiation therapy and most recovered without clinically significant neurologic deficits. There were no deaths due to transplant-related mortality. NRM occurred in 2 (4%) patients due to an unrelated cancer and stroke 1.1 and 4.3 years after ASCT, respectively. Among 27 patients &amp;gt;60 years old treated with ITT, 17 (63%) proceeded to ASCT, including 6 who received dose reductions of TT/Bu. The transplantation rate in this age group increased from 45% to 75% following the routine omission of Step 3. All 17 transplanted patients remain alive and in remission with median follow-up 2.5 years. Conclusion:In this real-world study of 71 patients with PCNSL, an abbreviated, low-intensity induction protocol resulted in high transplantation rates (~80%) and favorable long-term outcomes with 4-year OS 80%. Notably, TT/Bu conditioning achieved a low incidence of relapse with no transplant-related mortality observed, including among patients &amp;gt;60 years old. These data demonstrate that de-escalated induction therapy can result in improved rates of successful ASCT, thereby optimizing the outcomes of PCNSL.

Autologous Stem Cell Transplant in Fit Patients with Late Relapsed Diffuse Large B-Cell Lymphoma That Responded to Salvage Chemotherapy

Background: The new standard of care for fit patients with refractory or early relapse of diffuse large B-cell lymphoma (DLBCL) is chimeric antigen receptor T-cell (CAR-T) therapy. However, for patients with a relapse ≥12 months after completing frontline therapy, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) remains the standard of care. There is a need to characterize such patients and their survival in view of the recent shift in treatment paradigm. Methods: Patients with DLBCL that relapsed ≥12 months after R-CHOP or R-CHOP-like frontline therapy who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma and transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using Kaplan-Meier method and Cox proportional hazards models. Statistical analyses were performed in JMP v15. Results: A total of 158 patients with late relapsed DLBCL who underwent salvage chemotherapy and ASCT were identified. Baseline characteristics at relapse/ASCT are shown in Table 1. Median time from frontline therapy completion to 1st relapse was 26.4 months (range 12.0-152.4). Median age at relapse was 63 years (range 19-77), and 96 (61%) patients were male. A minority (3; 3%) had ECOG PS ≥2. 43 (52%) patients had an elevated serum LDH level, 70 (65%) had advanced stage disease, and 12 (11%) had &amp;gt;1 extranodal involvement. Median line of salvage therapy was 1 (range 1-3), and 17 (11%) patients required &amp;gt;1 line of salvage therapy. Best response before ASCT was complete response (CR) in 97 (61%) and partial response (PR) in 61 (39%). Median age at ASCT was 64 years (range 19-78). Median follow-up after ASCT was 91.5 months (95% CI 74.0-103.3). Median PFS and OS were 54.5 (95% CI 31.9-77.8) and 99.8 (95% CI 60.3-144.5) months, respectively. The 2-year PFS and OS rates were 64% (95% CI 56-71) and 81% (95% CI 74-87), respectively. No statistically significant difference in PFS was seen based on age at ASCT, sex, serum LDH, stage, or extranodal site involvement of &amp;gt;1 at relapse (Table 2). However, patients who required &amp;gt; 1 line of salvage therapy, compared to those requiring 1 line of salvage therapy, had significantly inferior PFS (median 6.1 vs 61.8 months, P &amp;lt;0.0001) and OS (17.8 vs 111.7 months, P &amp;lt;0.0004). There was no statistically significant difference in survival in patients who achieved CR vs PR prior to ASCT, with a median PFS of 61.8 vs 37.8 months( P=0.21) and a median OS of 111.7 vs 78.3 months ( P=0.62). Patients who achieved CR after 1 line of salvage therapy had the most favorable PFS and OS, with a median PFS of 65.6 vs 45.4 vs 6.1 vs 7.6 months ( P=0.0004) and a median OS of 133.0 vs 88.9 vs 24.2 vs 17.6 months ( P=0.004) in patients achieving CR after 1 line of salvage therapy vs PR after 1 line of salvage therapy vs CR after &amp;gt;1 line of salvage therapy vs PR after &amp;gt;1 line of salvage therapy, respectively (Table 2). In multivariate Cox regression models adjusted for age at ASCT and sex, patients requiring &amp;gt; 1 line of salvage therapy, compared to those who required 1 line of salvage therapy, had significantly inferior PFS with a hazard ratio (HR) of 3.25 (95% CI 1.82-5.78, P &amp;lt;0.0001) and OS with a HR of 3.50 (95% CI 1.86-6.60, P=0.0001). However, there remained no significant difference in survival based on response status (CR vs PR) with a HR for PFS 0.78 (95% CI 0.52-1.17, P=0.23) and OS 0.93 (95% CI 0.58-1.47, P=0.74). Conclusions: Survival after ASCT was excellent in patients with late relapsed DLBCL achieving CR after 1 line of salvage chemotherapy. Favorable survival outcomes were seen in patients who achieved PR after 1 line of salvage therapy. These data support the current clinical practice of ASCT consolidation in these patients. However, post-ASCT survival was poor in patients who required more than 1 line of salvage chemotherapy, despite achieving a satisfactory response to subsequent lines of salvage therapy. Alternative treatment strategies such as CAR-T therapy should be considered in such patients.

Total Body Irradiation Versus Chemotherapy-Only Conditioning in Autologous Hematopoietic Stem Cell Transplantation for Large B-Cell Lymphoma

Introduction Recent data suggest that compared with high-dose chemotherapy conditioning and autologous stem cell transplant (ASCT), CD19-chimeric antigen receptor (CAR) T-cell therapy as second-line therapy improves outcomes in patients with primary refractory or early relapsed large B-cell lymphoma (LBCL). However, more than half of patients will not attain a long-term remission with CAR T-cell therapy, and may subsequently be considered for ASCT, indicating an unmet need for alternative therapies including strategies to improve ASCT outcomes. Given that LBCL is radioresponsive, we evaluated whether total body irradiation (TBI)-based conditioning may improve outcomes compared to chemotherapy-only conditioning among LBCL patients who underwent peripheral blood ASCT at our institution. Methods We reviewed the records of adults with relapsed/refractory LBCL who underwent ASCT at Fred Hutch Cancer Center between 2012-2021. LBCL was categorized as de novo DLBCL, transformed DLBCL, and double-hit lymphoma (DHL). Patients with primary CNS lymphoma were excluded. Given that TBI is generally reserved for younger patients (≤ 60 years), we excluded patients in the chemo-only group older than the oldest patient in the TBI group (58.7 years) to reduce the bias due to age differences. The hazards for failure for progression-free survival (PFS) and for overall mortality (OM) were compared between TBI-based and chemo-only groups using Cox regression with adjustment for clinically important variables including age, sex, histology, LDH at ASCT, conditioning type, PET positivity at the time of ASCT and year of ASCT. LDH at ASCT, age and year of ASCT were modeled as continuous linear variables. Results Among 225 patients, we excluded 121 patients in the chemo-only group who were older than 58.7 years, leaving 104 patients for the analysis ( Table 1). A total of 48 (46%) patients received TBI-based and 56 (54%) received chemo-only conditioning. All patients in the TBI group received 12 Gy in 6-8 fractions. Most patients (n=46, 82.14%) in the chemo-only group received BEAM conditioning. Patients receiving TBI-based conditioning had more adverse features including male sex (72.9% vs 58.9%), DHL histology (31.3% vs 7.1%), and PET-positive disease at the time of ASCT (39.6% vs 23.2%). With a median follow-up of 51.2 months (range 1.3-134.2) among survivors, point estimates of PFS at 2 and 5 years were 74.3% and 66.3%, respectively among TBI patients and 68.5% and 64.0%, respectively among the chemo-only patients ( Figure 1). Time to engraftment was similar between the groups. On multivariable analysis, compared to chemo-only conditioning, TBI was not associated with improved PFS (TBI vs chemo-only: HR 1.02, 95%CI 0.45-2.31, P=0.96) or OS (HR 0.85, 95%CI 0.37-1.98, P=0.7). Predictors of worse PFS were PET positivity at the time of ASCT (HR 3.39, 95%CI 1.61-7.17, P &amp;lt; 0.01) and higher LDH (HR 1.0011, 95%CI 1.0002-1.0020, P=0.02). Similarly, both PET positivity (HR 3.12, 95%CI 1.47-6.63, P&amp;lt;0.01) and higher LDH (HR 1.0013, 95%CI 1.0003-1.0022, P &amp;lt;0.01) were associated with worse OS. Age, sex, histology and year of ASCT were not significant. Conclusions Despite worse prognostic factors, TBI-based conditioning yielded similar outcomes compared to chemo-only conditioning for patients with relapsed/refractory LBCL undergoing ASCT. These results confirm prior findings from a registry-based study. Although a proportion of patients may achieve a long-term remission with ASCT, other strategies are needed to improve ASCT outcomes.

Impact of interval progression before autologous stem cell transplant in patients with multiple myeloma.

In transplant-eligible patients who undergo upfront autologous stem cell transplant (ASCT) for multiple myeloma (MM), standard practice is to treat with six to eight cycles of induction therapy followed by high-dose chemotherapy with ASCT. A gap between the end of induction and the day of ASCT exists to allow stem cell mobilization and collection. Despite attempts to limit the length of this interval, we noticed that some patients experience interval progression (IP) of disease between the end of induction therapy and the day of ASCT. We analyzed 408 MM patients who underwent ASCT between 2011 and 2016. The median length of the interval between end of induction and ASCT was 38 days. We observed that 26% of patients in the entire cohort and 23.6% of patients who received induction with bortezomib-lenalidomide-dexamethasone (VRD) experienced IP. These patients deepened their responses with ASCT, independently of induction regimen. In the entire cohort, IP was significantly associated with shorter PFS in the univariable analysis (Hazard Ratio, HR = 1.37, P = 0.022) but not in the multivariable analysis (HR = 1.14, P = 0.44). However, analyzing only patients who received VRD as induction, progression-free survival (PFS) remained inferior in both the univariable (HR = 2.02; P = 0.002) and the multivariable analyses (HR = 1.96; P = 0.01). T cells and natural killer (NK) cells are increasingly studied targets of immunomodulatory therapy, as immune dysfunction is known to occur in patients with MM. Peripheral blood from 35 MM patients were analyzed. At time of ASCT, patients with IP had significantly increased percentages of CD3+CD8+CD57+ CD28- (P = 0.05) and CD3+CD4+LAG3+ (P = 0.0022) T-cells, as well as less CD56bright and CD56dim NK cells bearing activated markers such as CD69, NKG2D, and CD226. These data suggest that IP can impact the length of response to ASCT; therefore, further studies on the management of these patients are needed.

Peritransplant Radiation Therapy in Patients With Refractory or Relapsed Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant: Long-Term Results of a Retrospective Study of the Fondazione Italiana Linfomi

In this multicenter collaboration, we report real-world data in the largest published series of long-term outcomes for patients with relapsed/refractory (r/r) Hodgkin lymphoma (HL) treated with peritransplant radiation therapy (pt-RT) and high-dose chemotherapy with autologous stem cell transplant (ASCT). We conducted a retrospective analysis including data from 12 institutions. Eligibility required histologic diagnosis of HL, receipt of ASCT plus pt-RT between 2004 and 2014 for r/r HL, and age ≥18 years at the time of ASCT. All patients received salvage chemotherapy for maximum debulking before ASCT. Metabolic responses were scored according to the Lugano Classification. The primary endpoint was overall survival (OS). Univariate and multivariate Cox proportional hazards were calculated to estimate the effect of covariates on patients' outcome. One hundred thirty-one patients were eligible: 68 were male (52%), and median age at ASCT was 32 years (range, 18-70). At the time of diagnosis with r/r HL, 92 patients (70%) had limited (stage I-II) disease, and 10 patients (8%) had bulky disease. Pt-RT was given pre-ASCT in 32 patients (24%) and post-ASCT in 99 (76%); median prescribed dose was 30.6 Gy (range, 20-44 Gy). With median follow-up of 60 months, 3- and 5-year OS were 84% and 77%, while 3- and 5-year progression-free survival were 75% and 72%, respectively. On univariate and multivariate analysis, advanced stage at relapse (hazard ratio [HR], 2.18; P=.04), irradiation of >3 sites (HR, 3.69; P=.01), and incomplete metabolic response after salvage chemotherapy (HR, 2.24; P=.01) had a negative effect on OS. The sequencing of pt-RT (pre- vs post-ASCT) did not affect outcomes. Overall, the addition of pt-RT to ASCT for patients with r/r HL is associated with very good outcomes. Limited relapsed disease with ≤3 sites involved and achievement of complete metabolic response after salvage chemotherapy were predictive of more favorable prognosis.

Autologous Stem Cell Transplant in 2nd Line DLBCL in 2022, Still the Standard of Care ? a Monocentric Experience

Introduction: Patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) after frontline chemotherapy have a dismal prognosis. Salvage chemotherapy followed by high dose consolidation chemotherapy supported with autologous stem cell transplantation (ASCT) can achieve cure in about 50%, and remains the standard of care for fit patients under 70 yo. Nevertheless, this approach is less effective for patients with primo-refractory disease (refractory to 1st line CT or experiencing relapse during the 12 months after completion of 1st line treatment). With the advent of autologous CAR T cells targeting CD19 in second line of treatment, the place of ASCT must be redefined based on robust clinical data to offer candidate patients their best available treatment. As part of this "choose wisely" approach, we report the outcomes of patients receiving ASCT as consolidation therapy at our center. Methods: we report the retrospective experience of a monocentric transplantation program. Inclusion criteria were: 1) R/R DLBCL 2) In response to salvage therapy according to Deauville score criteria. Complete response (CR) was defined as Deauville scores 1-2-3, partial response (PR) as Deauville 4 or 5. 3) ASCT between 2010 and 2020 at IPC, Marseille 4) Conditioning regimen with BEAM or Bendamustine-Eam. The patients were stratified according to the NCCN-IPI in 2 groups: low risk (NCCN-IPI≤3) and high risk (NCCN-IPI>3). Univariate analyses included age, aaIPI, NCCN IPI and disease status pre ASCT. Multivariate analyse included disease status pre ASCT and NCCN-IPI Results: Ninety eight patients with a median age of 57 yo (26-71) were included. Most of them were primary refractory (52 patients, 53%). Patients received a median number of 2 lines of chemotherapy (2-4) before ASCT. At time of reinjection, all were in response (78% were in CR and 22% in PR). With a median follow up of 42 months (33-60), 3 year progression free survival (PFS) and overall survival (OS) were 68% and 82% respectively, and 3 year cumulative incidence of relapse (CIR) was 27%. In the whole group, 12 month NRM was 2%.Age was not associated with an increased risk of NRM (SHR 2.3 CI95 [0.44-12.24], p:0.3) . Three year PFS and OS were significantly higher in patients who underwent ASCT in CR: 3 years PFS 74% CR vs. 43% PR (HR 3.04 95CI [1.5-6.17], p: 0.001.), 3 year OS 88% CR vs 61% PR (HR 4.53 95CI [1.74-11.81 ], p< 0.001.). This was confirmed by multivariate analyse (HR 3.08 95CI [1.50,6.29] , p=0.0021 for PFS and HR 5.4 95CI [1.99-14.65 ], p=0.0009 for OS). Disease status at the time of ASCT and NCCN IPI >3 were strongly associated with PFS and OS (3 year PFS 71% CR and NCCN IPI ≤3 vs. 17% PR and NCCNIPI >3 (HR 5.62 95CI [2.03-15.54], p<.001 ) . Three year OS for CR and NCCN IPI ≤3 vs. PR and NCCNIPI >3 were: 86% vs. 17% (HR 16.15 95CI [4.87-53.57], p<.001). In the primary refractory group, 3 year PFS, OS and CIR were 70%, 75% and 22% respectively. No differences were observed with non primary refractory group (3 years PFS 66% vs. 70%, p=0.56 , 3 years OS 90% vs 75%, p= 0.077) Conclusion : We confirm that ASCT provides good disease control with few toxicity and remains a valid option in 2nd line DLBCL until 70 years of age. However, our results appear to be superior to previously published reports, even more in the group of primary refractory diseases, possibly due to a strict selection of patients achieving complete response after salvage therapy. Disease status before ASCT remains the most relevant parameter to predict survival, and should be incorporated in treatment decision algorithms to elect the optimal treatment sequence. Questions remain about the best strategy for patients in PR before ASCT, and we await long term results of randomized phase 3 CART cells studies (ZUMA7, TRANSFORM). According to our results, given the unfavorable prognosis of the group of patients in PR and NCCN IPI ≥ 3 could be the subgroup of patients that would most certainly benefit from CART cells. In conclusion, the best 2nd line strategy between ASCT and CAR T cells should be decided according to response quality, the access to CAR T cells program and economic impact. Moreover, the combination of pre treatment prognostic factors ( NCCN IPI) and pre-ASCT response to treatment could be even more halpful to choose the best consolidation treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Outcomes in Patients with Mantle Cell Lymphoma Who Received Autologous Stem Cell Transplant in the Second Line Setting

Background: Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with a variable clinical outcome. The standard of care for transplant-eligible patients has been to employ autologous stem cell transplant (ASCT) in first remission and this strategy is currently being tested in the NCTN trial EA4151. The utilization and outcomes of ASCT in second line (2L) treatment is unclear and this knowledge is important for those in the non-transplant control arm in EA4151. In this report, we studied the outcomes of patients who received ASCT in 2L for relapsed/refractory (R/R) MCL. Methods: Patients with newly diagnosed MCL between August 2002 and April 2015 were enrolled in the Mayo Clinic/University of Iowa Lymphoma SPORE Molecular Epidemiology Resource (MER) prospective cohort study. Patients who received ASCT at 2L, or at 1L as a reference group, were included in this study. Clinical characteristics and treatment details were abstracted from MER and by additional chart review. Event-free Survival (EFS) was defined as time from ASCT to progression, retreatment, or death due to any cause, and overall Survival (OS) was defined as time from ASCT to death due to any cause. Survival rates were generated using the Kaplan-Meier method in Rv4.1.2. Results: Among a total of 343 patients with MCL enrolled in the MER, 177 had disease progression or relapse following 1L therapy and had complete 2L treatment information available. Eighteen patients were considered for ASCT as part of 2L therapy. Two (11%) patients did not have an adequate response to 2L induction therapy, and 1 (6%) patient did not meet criteria due to failure of the stem cell mobilization and harvest. Therefore, 15 (83%) patients went on to receive ASCT at the 2L. For the 15 patients who received ASCT at 2L, 1L therapies were R-CHOP (N=9, 60%), rituximab and bendamustine (R-bendamustine, N=2, 13%), rituximab and cladribine (N=3, 20%); 1 (7%) received surgical intervention. All 15 patients were considered for ASCT at 1L. Eight (53%) did not proceed due to inadequate response or progression of disease in the 1L setting; 2 (13%) were treated on clinical trials at 1L that precluded ASCT (one with R-CHOP with 90Yibritumomab tiuxetan and the other with R-Bendamustine); 2 (13%) were considered low risk for relapse and deferred ASCT, and 1 (7%) decided not to proceed (patient decision); the reason was unclear in 2 (13%) other patients. The median time from diagnosis to 1L disease progression/relapse was 6.4 months (range 1.1-35.8). Of the 15 patients who received ASCT as 2L therapy, the median age at time of ASCT was 58 years old, 14 (93%) were male, 13 (87%) had stage III/IV disease, and MCL international prognostic index (MIPI) score was low in 5 (63%) and intermediate in 3 (38%) (MIPI missing in 7 patients). Induction therapy at 2L prior to ASCT included R-CHOP alternating with R-DHAP (N=1, 7%), Hyper-CVAD (N=2, 13%), R-CHOP (N=3, 20%), R-DHAP (N=2, 13%), R-EPOCH (N=1, 7%), ROAD (N=1, 7%), R-ICE (N=1, 7%), R-bendamustine (N=3, 20%), and ibrutinib (N=1, 7%). At a median follow-up of 6.3 years from transplant for patients receiving ASCT at 2L, 9 patients had disease progression or relapse, and 8 patients died (3 without known progression or relapse). The median EFS was 3.8 years and the 2-year EFS rate was 59% (CI 38-91%) and 5-year EFS rate was 37% (CI 18-73%). The 2-year OS rate was 73% (CI 54-99%) and 5-year OS rate was 60% (CI 41-91%). As a reference, 113 patients in the MER received ASCT in the 1L setting. The median EFS from date of ASCT was 5.2 years and the 2-year EFS rate was 77% (CI 70-85%) and the 5-year rate was EFS 54% (CI 45-64%). The 2-year OS rate was 86% (CI 80-93%) and 5-year OS rate was 79% (CI 72-87%). Conclusion: ASCT consolidation after salvage therapy in the 2L setting appeared feasible in select patients with R/R MCL. The PFS and OS outcomes following 2L appeared reasonable. In the evolving landscape of R/R MCL treatment, it is unclear whether ASCT will still have a role. It is possible that select patients with R/R MCL would still benefit from ASCT. Larger studies, although likely limited to retrospective setting, are needed to further evaluate the feasibility, outcomes, and prognostic factors of ASCT at 2L and beyond. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Worldwide Network for Blood and Marrow Transplantation (WBMT) Global Study on Baseline Characteristics and Clinical Outcomes in NEWLY Diagnosed Multiple Myeloma Patients Undergoing Upfront Autologous STEM Cell Transplantation, a Study Off 61,725 Patients from 629 Centers

Background: Patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics worldwide, likely due to variances in transplant activity, patient factors and health economic factors including access to new myeloma therapies. The first aim of this retrospective study was to analyze the global baseline patient characteristics and outcomes of upfront ASCT in NDMM. Methods: Data on patient characteristics and transplant outcomes for patients with NDMM who received an upfront ASCT between 2013 and 2017 were provided to the Worldwide Network for Blood and Marrow Transplantation (WBMT) by the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Australia and New Zealand Transplant and Cellular Therapies Registry (ANZTCT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant Group (LABMT), and the Ottawa Canadian Registry. There primary endpoints were overall (OS) and non-relapse mortality (NRM) and the secondary were progression-free survival (PFS) and relapse incidence (RI). The Kaplan-Meier estimator and log-rank test were used for OS and PFS, and the crude cumulative incidence estimator and Gray's test were used for competing events (RI and NRM). Age at ASCT, sex, year of ASCT, disease stage, Karnofsky score, MM classification, preparative regimen, time between diagnosis and ASCT, ISS stage at diagnosis, cytogenetic risk, and HCT-CI score were studied for prognostic value. Multivariable (cause specific) models included a random effect for each country and were censored at 3 years for OS and PFS and at 1 year for RI and NRM. Results: 61,725 patients from 629 centers (median patients/center = 67) were included: 61% from EBMT, 26% CIBMTR, 6% APBMT (5% Japan, 1% Taiwan, 0.3% Malaysia), 5% AZTCT, 1% EMBMT, 0.5% LABMT and 0.3% Ottawa, Canada. The patient baseline characteristics are shown in Table 1. Males comprised 58% and the median age at diagnosis was 60 years. The predominant phenotypes were IgG (54%), light chain (24%) and IgA (19%). The ISS stage at diagnosis was I (38%), II (35%) or III (27%) and cytogenetic risk was standard in 70% and high in 30%. The median time from diagnosis to ASCT was 7.1 months. The year of ASCT was equally distributed between 2013 and 2017 (the annual percentage varied between 18% and 22%). The median age at ASCT was 60.8 years with 5.1% of patients older than 70 years. The HCT-CI risk at transplant was low in 52%, intermediate in 25% and high in 23%. The Karnofsky score at ASCT was 100 in 40% and ≤90 in 60%.Disease status was CR in 19%, VGPR in 38%, PR in 36%, MR/SD in 5% and refractory in 2%. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) and 140 mg/m2 comprised 14%. Tandem ASCT was reported in 6.7%. Of the 11% of patients with data on post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5 to 41.6, IQR:19.2-60.4). Outcomes: non-relapse mortality (NRM) at 12 months was 1% (95% CI 1-2%); OS at 4 and 8 years was 76% (75-76%) and 45% (42-48%) respectively; PFS at 2 and 4 years was 65% (95% CI: 64-65%) and 40% (40-41%) respectively; RI at 6 and 12 months was 7% (7-7%) and 16% (15-16%) respectively. In the multivariate analysis (Table 2), later calendar year of ASCT, a better disease response at time of ASCT, higher Karnofsky score, and an IgG phenotype were all associated with an improved OS. A lower ISS stage, a lower HCT-CI score and standard risk cytogenetics were also associated with better OS (Table 2). Overall NRM was low. Younger age, higher Karnofsky score, higher melphalan dose, better disease response at ASCT, lower ISS stage at diagnosis and lower HCT-CI score were associated with a lower NRM. Conclusions: This study represents the largest study to date characterizing the outcomes of ASCT performed worldwide. The most frequent preparative regimen was melphalan 200 mg/m2. Unmeasured confounding (pre-existing toxicities/frailties) may partially explain the higher NRM in those with low dose melphalan. Globally, NRM was low at 1% at 12 months, while RI was 16%. Median OS was 7 years, median PFS was 3 years and differed across various risk factors. ASCT remains an effective and safe procedure for patients with NDMM world-wide. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Neutrophil to lymphocyte ratio (NLR) impact on the progression-free survival and overall survival of multiple myeloma patients treated with high-dose chemotherapy and autologous stem cell transplantation

High-dose chemotherapy with autologous stem-cell transplantation (ASCT) remains the standard of care in multiple myeloma (MM) patients. This retrospective study aimed to assess the impact of neutrophil-to-lymphocyte ratio (NLR) and other complete blood count (CBC)-based predictors on PFS and OS of transplant-eligible MM patients. The CBC-based biomarkers were evaluated in a single-center cohort of 176 MM patients at three time points: at the diagnosis, the time of ASCT, and +100 d after ASCT. Univariable and multivariable Cox’s regression analyses and Kaplan–Meier estimate were used in statistical analysis. NLR at ASCT (HR 1.15, 95% CI: 1.05–1.26) and hemoglobin at ASCT (HR 0.80, 95% CI: 0.68–0.94) were independent factors influencing PFS. In the model for OS, the only statistically significant factors were NLR at ASCT (HR 1.15, 95% CI: 1.04–1.27), bortezomib administration prior to ASCT (HR 0.52, 95% CI: 0.33–0.83) and age at diagnosis (HR 1.03, 95% CI: 1.00–1.06). NLR at ASCT is an independent predictive factor in MM patients undergoing ASCT.

Clinical significance of clonal hematopoiesis in the setting of autologous stem cell transplantation for lymphoma.

Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy-related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra-deep, highly sensitive error-correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T-cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5-year OS from the time of first relapse (39.4% vs. 45.8%, p= .043) and from the time of ASCT (51.8% vs. 59.3%, p= .018). The adverse prognostic impact of CH was not due to therapy-related myeloid neoplasms, the incidence of which was low in our cohort (10-year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p= .445). In terms of specific-gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13-2.67, p= .011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications.

Predictors of Relapse and Survival Following Autologous Stem Cell Transplant in Patients with Diffuse Large B-Cell Lymphoma

Background: Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with intensive chemotherapy and rituximab, 30-40% of patients will be refractory to or relapse after first line treatment. For these patients, the current standard of care is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). Prior studies have largely examined clinical risk factors associated with higher risk of relapse after ASCT; however, there is limited data integrating both pathologic and molecular features. Thus, we aimed to identify high-risk features associated with relapse and survival after ASCT using a combination of clinical, molecular, pathologic, and transplant characteristics.Methods: We retrospectively analyzed the medical records of all adult patients with DLBCL who underwent ASCT at our two institutions from 2010 to 2020. Patients with primary CNS lymphoma, primary mediastinal B-cell lymphoma, or Burkitt lymphoma were excluded. We analyzed demographics, clinical characteristics, cell of origin (COO) by immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH) testing, and treatment/transplant characteristics. The primary endpoints were 3-year progression-free survival (PFS) and overall survival (OS) from ASCT. The Kaplan-Meier method was used to estimate survival with univariate and multivariate Cox proportional hazards regression performed to identify factors associating with PFS and OS, summarized using hazard ratios (HR) with 95% confidence intervals (CI).Results: A total of 235 DLBCL patients underwent ASCT from 2010 to 2020. Median age at ASCT was 61 years (range: 25-75) and 63% were male. At DLBCL diagnosis, 80% had advanced stage disease, 74% had extranodal involvement, 13% had poor performance status, and 65% had elevated lactate dehydrogenase (LDH). 71 patients (30%) had a prior or concurrent indolent lymphoma diagnosis indicating transformed disease. Of the patients with available COO and molecular data, 115 (60%) had germinal center B-cell (GCB) phenotype by IHC, 10 (6%) had a single MYC rearrangement by FISH, and 35 (22%) had MYC plus BCL2 and/or BCL6 rearrangements (DHL/THL). After first-line treatment, 12% remained refractory and 62% later relapsed at a median of 13 months (range: 1-240). Patients received a median of 2 (range: 1-5) lines of treatment pre-ASCT. At time of ASCT, 66% were in complete response (CR) and 32% were in partial response (PR) by standard of care imaging and response criteria.With median follow-up of 5.2 years from time of ASCT, 98 patients (42%) relapsed and 78 (33%) died. 3-year PFS and OS were 58% (95% CI 51-64%) and 74% (95% CI 67-79%), respectively. In univariate analysis, factors associated with worse PFS and worse OS included 3 or more lines of treatment pre-ASCT (p<0.01 for both) and non-CR at ASCT (p<0.01 for both) (Figure 1A and B). Transformed disease was also associated with worse PFS (p=0.03). In multivariate analysis, non-CR at ASCT remained significant (HR 2.22, 95% 1.26-3.90, p<0.01) for worse OS, along with non-GCB COO (HR 1.81, 95% CI 1.03-3.18, p=0.04) and age >60 at ASCT (HR 1.92, 95% CI 1.06-3.47, p=0.03) (Figure 1C). Stratifying by COO and disease status at transplant, 3-year OS was best in the GCB/CR group (84%, 95% CI 73-90%), while worse but similar in the GCB/non-CR and non-GCB/CR groups (68%, 95% CI 51-80% and 71%, 95% CI 56-83%, respectively) (Figure 1D). The non-GCB/non-CR group had the worst 3-year OS (48%, 95% CI 27-67%). No individual factors beyond CR/non-CR at ASCT were associated with worse 3-year PFS. Notably, DHL/THL patients (77% of whom were in CR at time of ASCT) had similar PFS (p=0.08) and OS (p=0.30) to non-DHL/THL patients, suggesting that response to therapy may be more prognostic than high-risk molecular features alone.Conclusions: This analysis indicated that factors associated with OS after ASCT were disease status at time of transplant and COO, with non-GCB patients not in CR having the poorest outcomes. GCB patients not in CR were still able to be cured by ASCT at a high rate. Molecular rearrangements including DHL/THL were not prognostic, although interpretation may be limited by the modest number of DHL/THL patients. These findings may inform which patients should undergo ASCT, while the highest risk group may be better treated with alternatives including novel targeted agents or chimeric antigen receptor cell therapy. [Display omitted] DisclosuresBachanova: FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Fehniger: Compass Therapeutics: Research Funding; Affimed: Research Funding; ImmunityBio: Research Funding; Wugen: Consultancy, Current equity holder in publicly-traded company, Patents & Royalties: related to memory like NK cells, Research Funding; OrcaBio: Other; Kiadis: Other; HCW Biologics: Research Funding; Indapta: Other. Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding.

Autologous Haematopoietic Stem Cell Transplantation in Waldenström Macroglobulinemia: A Single-Centre 18-Year Experience

BACKGROUNDThe role of autologous stem cell transplantation (ASCT) in Waldenström Macroglobulinaemia (WM) is not well established, largely due to the paucity of evidence. It remains unclear where ASCT should be placed in the sequence of treatment lines. The debate is stronger in the era of targeted therapies that can achieve prolonged progression free survival (PFS) intervals and expected treatment-free intervals of approximately 4 to 8 years. The goal of this real world analysis was to review response and survival outcomes, and relapse risk factors in WM patients who underwent ASCT in a single WM referral centre.METHODSA retrospective cohort analysis was undertaken of consecutive WM patients treated with ASCT at a single specialist centre between 2003 and 2020. Baseline demographic/biological data, number/types of prior therapies, and pre- and post-ASCT depth of response, were collected from patient records and the WMUK Rory Morrison Registry. The primary aims were to determine depth of response, overall survival (OS), progression free survival (PFS), transplant related mortality (TRM) and relapse-associated mortality.RESULTSA total of 32 patients received ASCT, with a median age at time of ASCT of 57 years (range 40-68 years) and median interval from diagnosis to ASCT of 2.3 years (range 0.5-16.8 years); 14 (43.7%) were male. Prior to ASCT, 11 patients (34%) had received one therapy, 11 patients had 2 lines of treatment (excluding mobilisation), and 10 patients (31%) had received 3 or more therapies. The disease status pre-ASCT was complete remission (CR)/very good partial response (VGPR) in 14 patients (43.7%) and partial response (PR) in 18 patients (56.2%).Conditioning therapy comprised LEAM (Lomustine, Etoposide, Cytarabine, Melphalan; 18 patients, 56.2%), BEAM (Carmustine substituted for Lomustine; 12 patients, 37.5%), or Melphalan only (2, 6.2%). All patients had successful engraftment. Median time from stem cell reinfusion to hospital discharge was 15.5 days (range 13-187 days) in the 24 patients for whom these data were available; 5/24 patients (21%) were discharged >25 days after stem cell reinfusion. Restaging at 100 days post-ASCT showed deepening of response by ASCT in 17 patients (53.1%). CR/VGPR was achieved by 26 patients (81.2%) and PR by 4 patients (12.5%). Two patients (6.2%) experienced disease progression before day 100 post-ASCT (both receiving ASCT in second remission/PR2).At a median follow up of 8.9 years (range 0.1-18 years), the estimated median PFS was 4.5 years (95% confidence interval [CI] 3.2-5.7 years), with estimated 2-year and 5-year PFS rates of 75% and 35.9%, respectively (Figure 1A). In this small cohort, there was no significant difference in PFS based on age, number of prior lines of treatment, pre-ASCT remission status (CR/VGPR vs PR) or post-ASCT response achieved.At time of analysis, 14/32 patients (43.7%) had died: TRM rate was 6.2% (2 patients died during inpatient admission of ASCT complications), 4 patients (12.5%) died of PD, and 1 patient died of unknown causes. Another 7 patients (21.9%) died of infective causes after the immediate post-ASCT period: the median time from ASCT to death among these patients was 5.5 years (range 0.8-10.8 years). Estimated median OS for the unstratified cohort was 10.8 years (95% CI 7.3-14.3 years), with estimated 2- and 5-year OS rates of 87.5% and 77.5%, respectively (Figure 1B). Overall survival did not differ significantly based on age at time of ASCT, number of therapy lines prior to ASCT, pre-ASCT remission status (CR/VGPR vs PR) or post-ASCT response achieved.One patient (3.1%) underwent ASCT after BTK inhibitor therapy, achieving deepening of response (PR to VGPR) with ASCT and progression free interval of 11 months.CONCLUSIONASCT is a feasible treatment option for patients with relapsed WM, producing deeper responses following salvage therapy and resulting in PFS intervals comparable to other currently available therapeutic options. With the benefit of a long follow up period, performing ASCT at later stages in the treatment course (i.e. following 3 or more prior therapy lines) did not appear to result in inferior survival outcomes; timing of ASCT should therefore be considered on an individual patient basis and in light of other available therapy options for relapsed disease. [Display omitted] DisclosuresYong: Sanofi: Honoraria, Research Funding; GSK: Honoraria; Amgen: Honoraria; Autolus: Research Funding; BMS: Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Wechalekar: Amgen: Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy; Caelum Biosciences: Other: Clinical Trial Funding; Takeda: Honoraria; Celgene: Honoraria; Janssen: Consultancy. D'Sa: Sanofi: Honoraria; Janssen Cilag: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding.

Improvement in Outcomes of Autologous Stem Cell Transplant in Patients with Lymphoma Older Than 70 Years: The Significance of Age in 2020s?

Backgrounds: Autologous stem cell transplant (ASCT) has been the standard treatment approach for patients with relapsed or high-risk lymphoma for several decades. Despite the improvement in supportive care, age has remained one of the critical factors that determines transplant eligibility and outcomes. Herein, we explored the transplant-related outcomes of patients with lymphoma aged 70 years or older at our institution and compared to those with younger ages.Methods: In this retrospective single center study, we include all patients with diagnosis of lymphoma who underwent ASCT between January 2000 and February 2021 at Mayo Clinic, Rochester, Minnesota. In addition to data obtained from the transplant database, we abstracted data from electronic medical record. We described relevant clinical characteristics and transplant associated outcomes including engraftment, transplant related mortality, relapse incidence, and survival outcomes. We compared the key transplant related outcomes with patients at the younger age group between 65 and 70 years old.Results: A total of 196 patients with lymphoma aged 70 years or older underwent ASCT between January 2000 and February 2021. The median age of patients at the time of ASCT was 72.4 (70.0-78.7) years with 24 patients (12.2%) being older than 75 years old. Of 196 patients, 76 (38.8%) had Charlson comorbidity index of 3 or higher and 10 (5.1%) had performance status of 2 or higher at the time of ASCT. Table 1 summarizes the relevant baseline clinical characteristics of 196 patients in this cohort including the comparison with younger patients (age 65-70 years old, n=296). The most common transplant indication in this cohort was relapsed diffuse large B cell lymphoma. The majority of patients (91.3%) received peripheral blood graft with a median CD34+ cell dose of 5.14x10 6 cells/kg which was significantly lower than younger patients (P=0.01). The rate of neutrophil and platelet engraftment was 99.0% and 98.8% with corresponding median time to engraftment of 13 days for both cell lineages. The 30- and 100-day non-relapse mortality (NRM) of the entire cohort was 1.5% (95%CI 0-3.2%) and 4.6% (95%CI 1.6-7.5%) not statistically different between 70-75 years old and 75 years or older cohorts. With the median follow-up duration of 48 months, the 2-year event free survival (EFS) and overall survival (OS) was 55.9% (95%CI 49.2-63.5%) and 67.4% (95%CI 61.0-74.5%), respectively. Patients from the 70 years old or older cohort had similar EFS but inferior OS compared to the 65-70 years old cohort. However, there was no difference in EFS and OS between 70-75 and >75 years old cohorts. There was overall an improved trend of 30-day NRM, 2-year EFS and 2-year OS over the 3 different transplant periods (Figures). Although not statistically significant, patients who underwent ASCT between 2000 and 2006 had a trend towards higher 30-day NRM compared to patients who were transplanted at later time points (7.3% vs 0%, P=0.06). The major causes of death included progressive lymphoma, infection, and conditioning regimen related organ toxicities.Conclusion: Outcomes of ASCT in older patients with lymphoma have improved over time with an excellent 30-day NRM (0%) in the past recent years. The major cause of treatment failure after ASCT was progressive disease. With appropriate patient selection, ASCT in older patients is feasible and provides acceptable outcomes comparable to the patients from younger age group. [Display omitted] DisclosuresPaludo: Karyopharm: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding.

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.

Clinical Significance of Clonal Hematopoiesis in the Setting of Autologous Stem Cell Transplantation for Lymphoma

Clinical Significance of Clonal Hematopoiesis in the Setting of Autologous Stem Cell Transplantation for Lymphoma

Outcomes of Tandem Hematopoietic Stem Cell Autologous Transplant in High-Risk Myeloma Patients: A Single-Center Experience

Introduction: Studies have demonstrated that multiple myeloma (MM) is a clinically, genetically complex and heterogeneous disease. Cytogenetic alterations identify high-risk patients in MM and are associated with a poor prognosis. They include at least one of the following at diagnosis: t(4;14), t(14;16), t(14;20), del(17p), 1q amp and 1q amp + del(1p). Autologous stem cell transplantation (ASCT) and the development of novel agents have considerably increased the median survival of MM patients. Patients with high-risk cytogenetics are associated with worse survival, and studies have shown improvement in progression-free survival with tandem ASCT when compared to single ASCT.Methods: This is a retrospective single-center study evaluating MM patients with high-risk cytogenetics at our center who have undergone a tandem autologous transplant from January 1, 2017, to December 31, 2020. Primary objective was overall response rates (ORR) and relapse rates. Secondary objectives looked at progression-free survival (PFS), overall survival (OS) using the Kaplan-Meier method.Results: From January 1, 2017, to December 31, 2020, 25 high-risk patients underwent tandem ASCT. Key patient characteristics are shown in table 1. Translocation (4:14) was seen in 8/25 (32%) patients; t(14:16) in 5/25 (20%) patients; del17p in 7/25 (28%), 1q amp in 8/25 (32%) patients, del1p + 1q amp in 5/25 (20%) patients. In terms of double hit and triple hit disease, 9/25 (36%) patients had two high risk changes and 3/25 (12%) with had three high risk changes. ISS staging wise, 5/25 (20%) patients were ISS stage I, 5/25 (20%) patients ISS stage 2 and 9/25 (36%) patients were ISS stage 3. The most common induction regimen consisted of cyclophosphamide, bortezomib, and dexamethasone (CyBorD). One patient each transitioned to daratumumab, lenalidomide and dexamethasone and PAD/CVD due to poor response. Maintenance therapy was given to 21/25 (84%) tandem ASCT patients with 5 (20%) patients receiving lenalidomide, 4 (16%) patients receiving proteasome inhibitor and 12 (48%) patients received dual maintenance.In terms of response, we recorded CR (complete response) vs VGPR (very good partial response) vs PR (partial response) after induction, 2-3 months after ASCT #1, 2-3 months after ASCT #2, 12 months after ASCT #2, and 12 months after maintenance. Following induction, 16 patients had achieved VGPR, and 9 of patients had achieved PR. After ASCT #1, 5 (55.5%) PR patients deepened their response to a VGPR. 1-3 months post ASCT #2, 3 (33.3%) PR patients deepened to a VGPR, and 2 (12.5%) VGPR patients achieved CR. 12 months after ASCT #2, 2 of the previous VGPR patients (12.5%) achieved CR, and 1 PR (11.1%) patient achieved VGPR.At the median follow-up time of 60 months, 44% of patients had relapsed. 1 patient relapsed within 1-3 months post ASCT#1. Nine other patients relapsed post ASCT #2 and maintenance except one patient who relapsed at time of ASCT #2. Univariable analysis identified hemoglobin as a statistically significant association with risk of progression or death. All patients who received any maintenance after tandem transplant were progression-free at 60 months (p<0.001).Conclusion: In our retrospective study, results suggest that tandem ASCT allows for deepening of responses. Together with maintenance therapy, this contributes to the durability of further PFS prolongation in high-risk MM patients. [Display omitted] DisclosuresLam: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Amgen: Honoraria. Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

P-032: Clinical characteristics and outcome of 30 patients with poems syndrome in Catalonia: impact of autologous stem cell transplantation in first line and at relapse

<h3>Background</h3> POEMS syndrome is a rare paraneoplastic disease caused by an underlying plasma cell disorder. The aim of this study is to describe clinical and biological features as well as outcomes in a series of patients in a real-world clinical setting. <h3>Methods</h3> We retrospectively analyzed 30 patients with POEMS syndrome consecutively diagnosed and treated at 8 hospitals in Catalonia, Spain, between 1996 and 2021. Medical records were reviewed for clinical and lab features at diagnosis, first-line treatment, autologous stem-cell transplantation (ASCT) and outcomes including progression-free (PFS) and overall survival (OS). Diagnosis was stablished according to published diagnostic criteria (Dispenzieri A, Am J Hematol 2011). Median follow up of alive patients was 13 years. <h3>Results</h3> Median age of the series was 65 years (range, 42-86). The median serum M-spike was 5 g/L. The heavy chain isotype was IgG in 43% of patients and IgA in 40%, while the light chain isotype was lambda in 87%. Four patients had more than 10% bone marrow plasma cells. VEGF was available in 18 patients and 16 of them (88%) had increased levels (3 times greater than the superior limit). All patients presented peripheral neuropathy, and other clinical features included organomegaly (22 patients), extravascular volume overload (22), endocrinopathy (20), skin lesions (18), thrombocytosis (18) osteosclerotic lesions (17), polycythemia (7), papilledema (7), pulmonary hypertension (4), portal hypertension (4), and Castleman disease (7). The median time between onset of symptoms and diagnosis was 6.3 months. Treatment information was available in 29 patients. Four patients had an isolated bone lesion and received only local radiation therapy, with hematologic and clinical response in 2 of them and a 10-year OS of 87%. Twenty-three patients underwent an ASCT: 15 after chemotherapy (with or without additional radiation therapy) and 8 upfront. Median age at the time of ASCT was 54 years. Conditioning prior to ASCT consisted in melphalan 200 mg/m² in 74% of cases and 140 mg/m² in 26%. Among 20 evaluable patients for hematologic response, 10 achieved a complete response and 10 obtained a partial response (PR). Eleven (55%) of these hematologic responding patients also obtained a significant organ improvement in a median time of 7 months after ASCT (range, 4–11). Nine patients (41.7%) progressed at a median time of 5 years after transplant, 5 of them received a second ASCT and 3 achieved at least a PR. After the second ASCT, only one patient clinically progressed after 38 months. All the remaining patients remained in response at the last follow-up evaluation. Median PFS and OS of the series were 6 and 12 years, respectively. <h3>Conclusions</h3> In conclusion, in our experience ASCT proved to be highly effective for patients with POEMS syndrome. When progression is confirmed after the first transplant, a second ASCT may be performed with potential clinical benefit.

Autologous Stem Cell Transplantation For Adult Burkitt Lymphoma In The Rituximab Era: A Retrospective Study Of The Lymphoma Working Party (LWP) Of The European Group For Blood and Marrow Transplantation (EBMT)

IntroductionThe role of autologous stem cell transplantation (ASCT) for Burkitt Lymphoma (BL) in adults in the era of modern intensive chemotherapeutic regimes remains to be defined. The addition of Rituximab has been shown to improve outcomes in patients with BL, but how this influences outcomes for patients receiving ASCT is not clear. Prior studies of ASCT in BL have often included large number of patients treated with outmoded CHOP-like regimes, have often included children, and have combined outcomes of BL and Burkitt-like lymphoma (BLL). MethodWe conducted a retrospective registry based analysis of adult patients who were reported to the EBMT as having a diagnosis of BL and who had received an ASCT in the period of 2000-2011. Treatment history and histology reports were collected as part of the study. ResultsData including histology reports were returned for 125 patients who received a first ASCT between 2000 and 2011. Median age was 38.5y (range 16-64); 89 patients (71%) were male. While the diagnosis by pathology report was considered to be classic BL in 97 (78%) cases, the diagnostic possibility of BLL or atypical BL was considered in 28 (22%) cases. Twenty-one patients (17%) had stage I/II and 99 (80.5%) had stage III/IV disease. Fifty-one patients (53.7%) received Rituximab as part of 1st line treatment. Of all patients, 90 (74%), and 31 (25%) patients received ASCT in CR1/ VGPR1/PR1, and >CR1/ advanced disease (AD), respectively.5 year estimates for overall survival (OS) for the CR1 and VGPR1/PR groups were 80% and 71% respectively (p=0.23). Factor that was significant for OS in multivariate analysis (MVA) by Cox modeling, for the CR1/VGPR1/PR1 group was age <39 vs >39 (HR = 6.21 ; 95%CI 2.03-19 ; p=0.0013); status at transplant, i.e., PR1/VGPR1 vs CR1 (HR = 2.25 ; 95%CI 0.90-5.61) approached significance (p=0.081). Age >39 was the only significant risk factor for disease fee survival (DFS) in this group (HR = 3.11 ; 95%CI 1.27-7.6 ;p=0.0131). CNS involvement was a significant risk factor for relapse (HR 3.58, 95%CI 1.27-11.62, p= 0.017). Of note, administration of Rituximab as part of 1stline therapy did not appear to impact on OS or DFS. For patients receiving ASCT in CR>1 and AD, the OS was 59% and 25% respectively (p=0.042). Achievement of a subsequent CR had a significant impact on OS (HR 2.84, 95%CI 1.03-7.79, p=0.042) and DFS (HR 2.64, 95%CI 0.97-7.17, p=0.056). There was a trend for improved DFS for the BL vs the BLL patients that approached statistical significance (p=0.059). ConclusionIn this analysis of 125 adult patients with BL and BLL who received an ASCT in the era of intensive chemoimmunotherapy, disease status at transplant was the main determinant of outcome; age influenced OS and DFS for patients autografted in CR1/PR1/VGPR1. Prior Rituximab therapy did not predict post ASCT outcomes. Patients in PR1/ VGPR1 at the time of ASCT had outcomes that were not significantly inferior to those transplanted in CR1, and the former group of patients represent a subset who are most likely to derive a benefit from proceeding to an upfront ASCT. For those patients who have a chemosensitive relapse, ASCT offers the probability of salvaging a significant proportion. Patients with AD and chemoresistant disease had poor outcomes, and in such patients modalities of treatment other than ASCT should be pursued. Disclosures:Sureda:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Afanasyev:Alexion: Honoraria. Dreger:Riemser Pharma: Consultancy, Honoraria, Research Funding.