Abstract Multiple myeloma (MM) is a plasma cell malignancy with significant global disparities in outcomes owing to variable access to effective therapies. This study evaluates the clinical outcomes of patients with newly diagnosed MM (NDMM) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT) at King Hussein Cancer Center (KHCC) in Jordan. We included all adult patients with NDMM who underwent auto-HSCT after first-line induction at KHCC between 2009 and 2023. Data on frontline regimens, before and after HSCT responses, and survival outcomes were collected. Responses were assessed using the International Myeloma Working Group criteria. Kaplan-Meier estimates were used for overall survival (OS) and progression-free survival (PFS), with log-rank tests for comparisons. A total of 221 patients were identified. The median age at diagnosis was 54 years (range, 32-67). The most common frontline regimen was bortezomib, thalidomide, and dexamethasone (42%), whereas only 2% received lenalidomide. The overall response rate to frontline therapy was 95%, with 2% achieving stringent complete response (sCR), 13% CR, and 50% very good partial response. After auto-HSCT, the sCR and CR rates increased to 13% and 35%, respectively. With a median follow-up of 48 months (range, 6-201), the median PFS was 41.1 months (95% confidence interval [CI], 37.9-47.2), and the median OS was 92 months (95% CI, 72-119). In conclusion, auto-HSCT significantly deepens responses in patients with NDMM, particularly in resource-limited settings. However, limited access to maintenance therapies and novel treatments underscores the need for broader therapeutic options to optimize MM care in such settings.

The platform for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is evolving. Early immunosuppression initiation in peripheral blood haplo-HSCT with post-transplant cyclophosphamide was retrospectively assessed in 51 patients, showing high engraftment rates, low-grade CRS (35.3%), and favorable 3-year survival outcomes. Prospective studies are required to validate these results and optimize immunosuppression timing. Introduction: Peripheral blood (PB) grafts are increasingly used in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PT-Cy). The optimal timing for initiation of immunosuppression (IS) with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) in PB haplo-HSCT is unclear. This study evaluates the outcomes of early initiation of IS prior to PT-Cy. Methods: Medical records of adult patients with hematologic malignancies who received PB haplo-HSCT with PT-Cy between 2017 and 2022 were retrospectively reviewed. IS with CNI and MMF were started on day 0 and 1 postinfusion. Statistical analyses for survival outcomes were performed using the Kaplan-Meier method, and cumulative incidence (CI) models were used to account for competing risks for relapse, and nonrelapse mortality (NRM). Results: A total of 51 patients were included, with a median age of 37 years (range: 19-63) and a median follow-up of 44 months (range: 37.8-53 months). Neutrophil and platelet engraftment were achieved in 98% and 96% of patients, respectively. CRS occurred in 35.3% of patients, predominantly grade I, with only 1 patient developing grade II CRS. At 3 years, overall survival (OS) and progression free survival (PFS) were 51.8% and 50.2%, respectively, and GVHD-relapse free survival (GFRS) was 43.1%. The CI of relapse and NRM at 3 years were 28.2% and 21.6%, respectively. Conclusion: Early initiation of IS in PB haplo-HSCT was associated with high rates of engraftment, low rates of CRS, and favorable long-term survival outcomes. Prospective studies are needed to validate these findings and refine IS timing.

Despite the availability of novel agents, autologous hematopoietic cell transplantation (auto-HCT) remains the standard of care in newly diagnosed multiple myeloma (MM) patients. The impact of age on overall survival (OS), progression-free survival (PFS), relapse incidence, non-relapse mortality (NRM), and excess mortality (taking account of general population mortality) was investigated using information on 61,797 MM patients transplanted between 2013 and 2017. The median age at auto-HCT was 60.8 (range: 18.1–83.2) years of whom 2.0% were 18–39 years, 68.9% 40–64 years, 21.8% 65–69 years, 6.5% 70–74 years, and 0.8% ≥75 years of age, respectively. The corresponding OS probabilities at three years were 85.9%, 82.8%, 81.1%, 78.4%, and 74.8%, respectively (p<0.001). Excess mortality cumulative incidences were 13.1%, 15.0%, 14.6%, 15.0%, and 14.1% at three years, respectively (p=0.67). In multivariable analyses, older age was a significant risk factor for OS, PFS, and NRM but not for excess mortality or relapse risk. Our results indicate that advanced age alone should not preclude the use of auto-HCT in patients with MM.

Introduction: Despite recent advances in multiple myeloma (MM) treatment, autologous transplant (HCT) remains essential for management of patients especially in areas where access to novel therapies is limited. Regional variations in treatment access and healthcare resources can affect patient outcomes. This study aims to evaluate the outcomes of MM patients undergoing HCT at King Hussein Cancer Center (KHCC) in Jordan, assessing the effectiveness of treatment in a setting with limited resources. Methods: We performed a retrospective cohort study of MM patients who underwent HCT at KHCC between 2009 and 2023. Data were extracted from electronic medical records, including demographics, disease characteristics, treatment regimens, and clinical outcomes. Response assessments were performed according to the International Myeloma Working Group (IMWG) criteria. Key outcomes assessed were overall survival (OS) and progression-free survival (PFS). OS was defined as the time from diagnosis to death from any cause, while PFS was defined as the time from HSCT to disease progression or death. Survival analyses were conducted using the Kaplan-Meier method, and differences in survival rates were evaluated using the log-rank test. Results: The study included 317 patients, with a median age at diagnosis of 53 years (range: 26-69 years). The cohort was predominantly male (61%). The most frequent presenting symptom was bony pain in 63% of patients. Two or more presenting symptoms were seen in 39 (12.3%) patients. At diagnosis, 76% of patients had bony lesions, and approximately 35% had fractures. About 16% of patients had more than one fracture at diagnosis, and more than half of all patients (52.1%) had more than 5 lesions at diagnosis. Almost a fourth of all patients had low albumin (<3.5g/dL), and 16% had high LDH at diagnosis. The most common light chain was Kappa (59%), and the most common heavy chain was IgG (56.2%). Cytogenetic data were available for 211 patients (66.5%). The most common International Staging System (ISS) stage was Stage III in 38% of patients. Induction regimens included bortezomib, cyclophosphamide, and dexamethasone (VCD) (17%), bortezomib, thalidomide, and dexamethasone (VTD) (37%), thalidomide and dexamethasone (TD) (13%), cyclophosphamide, thalidomide, and dexamethasone (CTD) (7%), and others (26%). Overall response to induction therapy was achieved in 73% of patients, with only 16% having lenalidomide exposure upfront. All patients received at least one HCT, with 17% undergoing more than one. The median number of pre-transplant therapy lines was one (range: 1-5). Post-first transplant, 92% of patients achieved at least a partial response, including 13% with stringent complete response (sCR), 33% with complete response (CR), 29% with very good partial response (VGPR), and 16% with partial response (PR). In those with VGPR pre-HCT, 14 (9.7%) attained sCR, 55 (38.4%) achieved CR, 62 (43.3%) remained in VGPR. Among patients with PR pre-HCT, 11 (10%) attained sCR, 21 (19.2%) achieved CR, 25 (23%) achieved VGPR, 40 (36.7%) remained in PR. Relapse occurred in 48% of patients, with a median PFS of 31.5 months. The PFS did not differ significantly based on induction regimen or prior lenalidomide exposure. Maintenance therapy was administered to 10% of patients, with 22 receiving lenalidomide and 8 receiving thalidomide. Patients who had responses less than CR prior to HCT but achieved CR after HCT exhibited similar outcomes to those who were in CR before HCT. For patients undergoing a second transplant, the median PFS was 22.7 months (95% CI: 14.5-30.9 months). A response to the second transplant was observed in 93% of patients, with 31 experiencing relapse. By the end of the follow-up period, 36% of patients had died. The median OS was 99 months (95% CI: 78-120 months). There was no significant variation in OS based on induction regimen, prior lenalidomide exposure and/or initial presenting symptoms. Conclusions: While the role of HCT in the management of MM is being challenged worldwide, patients still derive significant benefits from HCT in settings with limited access to novel therapies. Overall survival rates are promising with median survival of more than 8 years for patients who underwent autologous HSCT. However, challenges such as relapse persist with limited treatment options, highlighting the need for continued advancements in treatment strategies to improve long-term outcomes.

Rationale: Early relapse (ER) within 12 months of Autologous Hematopoietic Stem Cell Transplantation (AHCT) is currently accepted as functional high risk among patients diagnosed with Multiple Myeloma (MM). Efforts to predict ER has led to different risk scores developed by CIBMTR, GIMEMA and EBMT. CIBMTR and GIMEMA score integrates parameters not always available (bone marrow plasma cell percentage prior to AHCT, lambda light chain, FISH and LDH), whereas the EBMT score includes very simple factors ISS (at diagnosis), performance and disease status (prior to AHCT) (Beksac et al BMT 2023). EBMT ER score was developed using data obtained from patients aged 40-70 with a first AHCT in mainly European transplantation centers. This retrospective study aims to validate the EBMT ER score using data from a worldwide cohort of AHCT MM patients. This large population differs from the one used in the original paper, by age range, the number of countries and ethnicities, features in favor of suitability for external validation. Methods: We selected patients from the WBMT study, a collaboration of five MM transplantation registries around the world. Only registries with data available on all components of the EBMT score were selected. Patients included in WAUSTIM had a first AHCT between 2013-2017. EBMT data within this current study belonged to only 2013 which was not included in the original study. We used Cox proportional hazards regression and the c-index to measure the predictive discriminative performance of the EBMT ER score. Results: In total 14,924 patients (EBMT (4.1%), CIBMTR (79%), Australia and New Zealand (2.8.%), Japan (14%) and EMBMT (0.2%) were included. Median age at AHCT was 61(25-83) years. IgG (56%), IgA (21%) and light chain (21%). Disease status at the time of AHCT was CR (16%), VGPR (39%), PR (39%), SD/MR (6%), Rel/Prog (0.3%): ISS at diagnosis was I/II/III: 38/36/27%; Karnofsky score prior to AHCT-1: ≤70/80/90/100: 12/29/41/18 %. Cytogenetic risk was standard/high (t(4;14),t(14;16),17pdel) in 69%/31% of those with data available (not available in 17%). 81%/16% received Mel200/Mel140. Maintenance treatment was unknown for 89%. EBMT ER score distribution was: 0/1/2/3/4: 18%/32%/31%/14%/3.5%. Within the Mel200 only population restricted to the 40-70 age limit (as in the original study), after a median FU of 48 months 12-month PFS (PFS-12) was 84% (95% CI 83-84%) with an ER incidence of 14.7%. which is similar to that observed in the original EBMT study (Mel200 training: 14.7%, Mel200 validation: 11.6%, Mel140: 16.9%). The score 0/1/2/3/4 distribution was: 19%/34%/31%/13%/3.2%. Thus the prevalence of scores 0-4 within the original and the current study are similar as well. PFS-12 (95% CI) according to scores were as follows: score 0: 90 (89-91); score 1: 86 (85-87); score 2: 83 (82-84); score 3: 78 (76-80); score 4: 69 (64-74) resulting with HRs vs score 0: score 1: 1.42; score 2: 1.75; score 3: 2.32; score 4: 3.69 (all p values<0.001. The c-index was 0.58 without and 0.61 with cytogenetic risk included. EBMT ER score acts similarly within this worldwide population with a clear separation of curves between scores 0-4. Cytogenetic high risk vs standard risk HR: 1.88 (95% CI: 1.69-2.09) among Mel200 and 1.81(95% CI: 1.65-1.98) were among the whole population(p-value<0.001). Comparison of the original study HRs and score points with the current analysis will be presented at the meeting. Similar analysis performed among the whole population not limited to age or conditioning regimen intensity, resulted with highly similar PFS-12 ranging between 90-69% for scores 0-4 with HRs 1.39-3.49 (scores 1-4, all p-values <0.001; high vs standard risk HR: 1.81; C index: 0.58 without cytogenetic, and 0.61 with cytogenetic). Conclusion: In a population from various parts of the world, we have been able to validate the EBMT ER score among both Mel200 and Mel140 conditioned myeloma patients with a wider range of age at AHCT-1. Although the cytogenetic risk score provided additional predictive value in the original and current study, it had no modification effect on the EBMT ER score. Due to high rate of maintenance data missingness, we could not investigate the role of the score when patients were continued to be treated after AHCT. Based on our findings, EBMT ER score is a predictive tool for recognition of functional high risk MM patients at the time of AHCT-1.

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

Background： In eligible newly diagnosed myeloma patients, autologous hematopoietic cell transplantation (AHCT) is the standard of care. The most important prognostic factors are response status at the time of AHCT and receipt of maintenance therapy. Len maintenance post AHCT improves progression-free survival (PFS) and overall survival (OS). Using a global registry, we analyzed whether Len or Thal maintenance can overcome a suboptimal hematological response at AHCT. Methods: Data were provided by the Worldwide Network for Blood and Marrow Transplantation (WBMT) through 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 Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant group (LABMT), and the Ottawa hospital myeloma registry. The study included newly diagnosed myeloma patients receiving AHCT between 2013 and 2017 with data available on maintenance treatment. The primary endpoint was OS and secondary endpoints were PFS, Multivariable 6-month landmark analyses were performed using Cox proportional hazards models including a random effect for country. Apart from maintenance post AHCT (Len vs. Thal vs no maintenance) and hematological response at AHCT, models included patient sex, year of AHCT, Karnofsky score at AHCT, myeloma subclassification, conditioning dosage, interval between diagnosis and AHCT, HCT comorbidity index, ISS at diagnosis, and cytogenetic risk score. Results: Among the 61,797 patients in the WBMT study, 11% had information on maintenance. Fifty-one percent had Len (3460 pts), 38% other than Len (2640 pts, including 672 with Thal) and 11% none (767 pts). We report characteristics of the 4903 patients with Len, Thal or no maintenance (47.0% EBMT, 33.9% CIBMTR, 10.4% APBMT, 0.9% EMBMT, 4.4% LABMT, 3.4% Canada) and include 4555 of these who were alive at 6 months post-AHCT in the OS and 4334 who additionally were without relapse in the PFS analysis. The median age at AHCT was 60.0 (IQR: 53.7-65.5) years. Response status at AHCT was: complete response (CR) (19%), very good partial response (VGPR) (39%), partial response (PR) (36%), stable disease/minor response (SD/MR) (5%), relapse/progression (Prog) (1%). Median follow-up after AHCT was 45 months. In univariable analyses, Len and, to a lesser extent, Thal maintenance was associated with improved OS, PFS, lower RI and NRM (all p<0.001) compared to no maintenance. Improvements were observed regardless of disease status at HCT. OS at 3 years for CR, VGPR, PR and SD/MR/Prog patients was 82%, 80%, 81% and 72% in those without maintenance and was 92 (+10)%, 89 (+9)%, 88 (+7)%, 84 (+12)%, respectively for those with Len, (log-rank p<0.001). PFS at 3 years ranged from 61, 54, 45 and 35% without maintenance to 72 (+11)%, 68 (+14)%, 63 (+18)%, 58 (+23)% with Len for CR, VGPR, PR and SD/MR/Prog patients, respectively (log-rank p<0.001). In the MVA, better response status at AHCT, and Len maintenance were significantly associated with better OS and PFS. The OS and PFS HR (95% CI) comparing no maintenance vs Len were 1.92, (1.52-2.43), p=0.0004 and HR 1.74 (1.51-2.02) p<0.0001, respectively. The OS HR (95% CI) for VGPR, PR, SD/MR and Rel/Prog vs CR at AHCT was 1.07 (0.82-1.40), 1.23 (0.94-1.61), 1.79 (1.18-2.72) and 2.71 (1.55-4.74), respectively, (overall p=0.0003). For PFS, these estimates were 1.12 (0.95-1.32), 1.43 (1.21-1.68), 1.78 (1.37-2.32) and 2.10 (1.40-3.15), respectively (overall p<0.0001). In the MVA for OS, the benefit of Len maintenance decreased with longer time after AHCT (non-proportional hazards p=0.0002). The HR for no maintenance vs. Len decreased from 3.89 (95% CI 2.55-5.93) at 6 months to 1.02 (95% CI 0.67-1.54) at 36 months. For PFS, a less strong decrease in the HR over time was observed (p=0.05). The HR comparing no maintenance vs Thal for OS was 1.38 (0.98-1.95) and for PFS was 1.21 (0.98-1.49), p=0.06 and 0.07, respectively. Conclusions: In this global study of myeloma patients who underwent upfront AHCT, Len maintenance improved PFS and OS, as shown in other studies. Patients with CR as well as those with suboptimal response at AHCT benefit from Len maintenance. Thal, more broadly available globally than Len, was associated with a lesser non-significant trend towards improvement in OS and PFS compared to no maintenance.

Background: Worldwide, patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics and survival outcomes, likely due to variances in transplant activity, patient and health economic factors including access to new myeloma therapies. The goal of this retrospective study was to analyze differences in regional outcomes. 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). Results: 61725 patients from 629 were included: 37549 (61%) from EBMT, 16217 (26%) CIBMTR), 3815 (6%) APBMT (3122 Japan, 524 Taiwan and 169 Malaysia), 3,164 (5%) ANZTCT, 543 (0.9%) EMBMT, 339 (0.5%) LABMT and 188 (0.3%) Ottawa). The annual number of ASCTs steadily increased between 2013 (n=11317) and 2017 (n=13498) with the biggest relative increase seen in LABMT (from 36 to 109). Males comprised 58% and the median age at diagnosis was 59.9 years (IQR: 53.6-64.9). Race data was available in 45%: 73% White, 16% Asian and 11% African American. The predominant phenotypes were IgG (54%), light chain (24%) (lowest (4%) in Malaysia and highest (38%) in EMBMT), and IgA (19%) (lowest (13%) in EMBMT and highest (24%) in Ottawa). The ISS stage at diagnosis (54% available) was I in 38%, II 35% and III 27% (III lowest (24%) in ANZTCT and highest (45%) in LABMT). Cytogenetic risk (44% available) was standard in 70% and high in 30% (high risk was lowest (5%) in EMBMT, and highest (62%) in Ottawa). The median time from diagnosis to ASCT was 7 months (IQR:5.5-9.9) (shortest (6.4) in CIBMTR and Ottawa, and longest (13) in LABMT). The median age at ASCT was 60.8 years (IQR: 54.6-65.8) (lowest (53.6) in EMBMT, and highest (62) in Ottawa). Only 5% of patients were older than 70 years (lowest (3.5%) in EBMT, and highest (9.8%) in CIBMTR). HCT-CI at ASCT (28% missing) was reported as low risk (0) in 52%, intermediate (1-2) 25% and high risk (≥3) 23% (high risk was lowest (5.5%) in LABMT and highest (42%) in CIBMTR). The Karnofsky score at ASCT (2.2 % missing) was 100 in 40% and ≤90 in 60% (≤90 was lowest (44%) in LABMT and highest (92%) in Ottawa). Disease status (9.7% missing) was CR in 19%, VGPR 38%, PR 36%, MR/SD 5% and refractory 2%. A ≥VGPR status at ASCT was 60% in EBMT, 55% CIBMTR, 39% ANZTCT, 51% Japan, 64% EMBMT, 71% Taiwan, 76% LABMT, 51% Ottawa and 54% Malaysia. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) (lowest (60%) in Malaysia and highest (90%) in Ottawa), 140 mg/m2 accounted for 14% and others for 4%. Tandem ASCT was reported in 6.7% (10% in EBMT, 1.3% in CIBMTR and 0.6% LABMT and Taiwan). The source of stem cells was peripheral blood in 99.8%. Of the 11% reported with post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5-41.6, IQR:19.2-60.4). Regionally, at 3 years, the OS was : 81%, 84%, 82%, 83%, 77%, 75%, 84%, 82%, 69% (p<0.001), the PFS was 46%, 55%, 48%, 63%, 44%, 53%, 56%, 53%, 43% (p<0.001) (Figure) and the RI was:16%, 15%, 16%, 17%, 24%, 16%, 16%, 13%, 24% (p<0.001) for EBMT, CIBMTR, ANZTCT, Japan, EMBMT, Taiwan, LABMT, Ottawa and Malaysia, respectively. NRM at 1 year was between 1-2% in each registry (Figure). Conclusions: This large worldwide study of patients with NDMM treated with upfront ASCT revealed marked regional differences in transplant activity and patient characteristics. NRM was low worldwide but with differences in relapse incidence and survival potentially reflect variable health economic factors, including different access to new myeloma drugs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

BACKGROUND AND OBJECTIVES Almost 25% of patients with lymphoma may have relapse or develop refractory disease, and a majority of such patients undergo salvage chemotherapy and autologous stem cell transplantation (ASCT). Data on venous thromboembolism (VTE) in this setting are scarce. This study aimed to investigate the prevalence and factors that may increase the risk of VTE in such patients. PATIENTS AND METHODS Adult patients who were diagnosed with lymphoma and received salvage chemotherapy and ASCT were included in the study, and the subgroup with radiologically confirmed VTE were identified. Correlations between different clinical and laboratory variables and VTE were evaluated. RESULTS A total of 216 patients (median age, 31 [range, 19-60] years) were enrolled in the study. Most patients (n = 140, 64.8%) had Hodgkin's lymphoma, while 54 (25.0%) had diffuse large B-cell lymphoma. A total of 36 (16.7%) patients had VTE, mostly as upper extremity deep vein thrombosis (n = 28, 77.8%); 18 (50%) of the cases were related to central venous catheter insertion. Thrombosis rates were higher among patients with high lactate dehydrogenase (LDH) level (29.2% vs. 5.9%, p < 0.001), those with mediastinal involvement (25.9% vs. 11.5%, p = 0.025). and those with longer hospital stay (22.3% vs.9.5%, p = 0.036). In the multivariate analysis, high LDH level (odds ratio (OR), 6.53; p < 0.001), mediastinal involvement (OR, 2.70; p = 0.005) and hospital stay ≥24 days (OR, 2.71; p = 0.007) were all associated with significantly higher VTE rates. CONCLUSION Patients with relapsed lymphoma undergoing salvage chemotherapy and ASCT are at higher risk for VTE, especially in those with high LDH level, mediastinal involvement, and prolonged hospital stay. If no contraindications exist, thromboprophylaxis might be considered in these settings.

Background ： Induction therapy with proteasome inhibitors and immunomodulatory agents followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care in front line multiple myeloma (MM) treatment. Utilization of autologous HCT is increasing worldwide in younger and older patients in light of improvements in supportive care and infrastructure. However, global perspectives on patterns of patient age and the impact of age on outcomes in this population are scarce. In the current analysis of global registry data, we focused on the age distribution and the association of age with outcomes after HCT worldwide. Methods: Data were provided by the Worldwide Network for Blood and Marrow Transplantation through the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Australia and New Zealand Transplant and Cellular Therapy Registry (ANZTCTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant group (LABMT), and the Ottawa hospital myeloma registry. The study included newly diagnosed MM patients transplanted between 2013 and 2017. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), incidence of relapse, and non-relapse mortality (NRM). The probability of OS and PFS was estimated based on the Kaplan-Meier method and differences were analyzed using the log-rank test. The incidences of relapse and NRM were modeled using the crude cumulative incidence estimator and compared between groups with Gray's test. Multivariate analyses were performed using Cox (cause-specific) proportional hazards models including a random effect for country. Age at HCT was modeled as a categorical variable (18-39, 40-64, 65-69, 70-74, and ≥75 years). Models further included patient sex, year of HCT, stage of disease at HCT, Karnofsky score, myeloma subclassification, conditioning dosage, interval between diagnosis and HCT, HCT comorbidity index, ISS at diagnosis, and cytogenetic risk score. Results: In total, 61,725 patients were included in this study; 37,459 (60.1%), 16,217 (26.3%), 3,164 (5.1%), 3,122 (5.1%), 543 (0.9%), 524 (0.8%), 339 (0.5%), 188 (0.3%), and 169 (0.3%) from EBMT, CIBMTR, ANZTCTR, Japan (APBMT), EMBMT, Taiwan (APBMT), LABMT, Ottawa, and Malaysia (APBMT), respectively. The median age at HCT was 60.8 (interquartile range: 54.6-65.8) years. The percentage of patients in the age groups 18-39, 40-64, 65-69, 70-74, and ≥75 years, varied considerably; 2%, 68.9%, 21.8%, 6.5%, and 0.8%, respectively (Table 1). The proportion of <40 years was higher in Malaysia, LABMT, and EMBMT (4-6%) compared to EBMT, CIBMTR, Japan, and ANZTCTR (2%). In contrast, the proportion of patients ≥65 years was higher in EBMT, CIBMTR, ANZTCTR, and Japan (>20%) compared to Malaysia, LABMT, and EMBMT (7-13%). The following patterns were observed in the age groups 18-39, 40-64, 65-69, 70-74, and ≥75 years, respectively. Melphalan 200 mg/m 2 for conditioning was used more frequently in younger patients (78.4%, 75.4%, 63.2%, 40.6%, and 28.3%, respectively). In 60.7% of the group ≥75 years, a lower dose of melphalan 140 mg/m 2 was chosen. OS was lower with older age (p<0.001) and was 86%, 83%, 81%, 78%, and 75% at 3 years, respectively (Figure and Table 1). PFS was similarly associated with older age (56%, 51%, 50%, 47%, and 45% at 3 years, respectively (p<0.001)). The cumulative incidence of relapse was not significantly different (15%, 16%, 15%, 16%, and 16% at 1 year, respectively (p=0.74)), but the cumulative incidence of NRM was higher with older age (p<0.001) and was 0%, 1%, 2%, 2%, and 4% at 1 year, respectively. On multivariate analysis, older age was associated with lower OS (overall p<0.0001), lower PFS (overall p=0.003), and higher NRM (overall p<0.0001), but not with the risk of relapse (overall p=0.79). Conclusions: There is considerable global variability in the age distribution of patients receiving HCT. Globally, 2% of patients receiving front line HCT for myeloma are aged <45 and 0.8% are >75 years. Advancing age was a significant risk factor for OS and PFS due to differences in NRM, but even in patients >75 years NRM was very low.

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

There is a need for more research focusing on multiple myeloma in young patients regarding epidemiological landscape, disease biology, and clinical management.

Background Primary isolated extra-medullary plasmacytoma (EMP) is a rare entity that most commonly involves the nasopharynx or upper respiratory tract. Only 10% of cases involve the gastrointestinal tract, mainly the small intestine and the stomach. Involvement of the colon is extremely rare with less than 40 reported cases worldwide. Case Presentation We report a case of a 57-year-old man who was presented with a 3-week history of fresh bleeding from the rectum. Colonoscopy showed a polypoidal mass arising from the ascending colon; biopsy showed clonal plasmacytosis and a primary colonic solitary EMP diagnosis was made after exclusion of multiple myeloma (MM). Accordingly, the patient underwent a right hemicolectomy, followed by 6 cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD). The patient continued to be disease-free 30 months after the completion of his chemotherapy. Conclusion To our knowledge, this is the first reported case of primary colonic plasmacytoma managed with surgical resection followed by an adjuvant bortezomib-based regimen with a durable response.

In multiple myeloma (MM), high dose chemotherapy (HDC) and autologous hematopoietic stem cell transplant (ASCT) is still considered the standard of care. The decision to proceed to the second of a tandem transplant is based on degree of response at disease evaluation on or near day 100 (D100) post-transplant. Whether patients who achieve further response beyond D100 do as well as patient who achieve complete response (CR) at D100 and so can forgo a second transplant is unknown.

The risk of thromboembolic events is higher among cancer patients, especially in patients undergoing chemotherapy. Cisplatin-based regimens claim to be associated with a very high thromboembolic rate. In this study, we report on our own experience with thrombosis among patients on active cisplatin-based chemotherapy.