Received Stem Cell Transplantation Research Articles

Management of patients with acute lymphoblastic leukemia in routine clinical practice: Minimal residual disease testing, treatment patterns and clinical outcomes in Belgium, Greece and Switzerland

ObjectivesTo describe real-world management and clinical and economic outcomes of patients with B-cell precursor acute lymphoblastic leukemia (ALL) in Belgium, Greece and Switzerland. MethodsThis descriptive, retrospective medical chart review collected patient-level data in 2018 from adults with ≥1 minimal residual disease (MRD) test during front-line ALL treatment. Data were stratified by MRD status. ResultsEighty-two patients were included (median age 44 years, 23 % Philadelphia chromosome-positive; MRD-positive: n = 17, MRD-negative: n = 50, MRD result unknown: n = 15). HyperCVAD (32 %) and HOVON (26 %) were the most frequently used front-line treatment protocols; 22 % of patients received stem cell transplantation. Overall, 76 % of ALL patients were hospitalized (mean 1.1 hospitalization/month). Complete hematological response (CRh) occurred in 66/82 patients (80 %). Median relapse-free survival from CRh was 32.7 months (MRD-positive: 11.7 months; MRD-negative: 33.3 months). Median overall survival from diagnosis was 28.9 months (MRD-positive: 15.3 months; MRD-negative: not reached). Most patients (88 %) were MRD tested during induction; testing rates considerably decreased thereafter (39 % during consolidation). ConclusionsB-cell precursor ALL represents a clinical burden and impacts healthcare resources; MRD-positive patients have worse prognosis than MRD-negative patients. Efforts should be made to adhere to recommendations for MRD testing in clinical guidelines.

Retrospective Evaluation Of Children After Stem Cell Transplantation: Single Center Experience

AbstractAim: Analysis of the data of children following stem cell transplantation.Materials and Methods: A total of 44 children who received stem cell transplant between February 2009 and May 2011 were evaluated retrospectively. Results: Among the patients with a mean age of 9.6 ± 4.63 years, 20 (45.5%) were male, whereas 24 (54.5%) were female. The initial diagnosis of the patients with decreasing order of frequency was as follows: thalassemia major (n=15), acute leukemia (n=9), Fanconi aplastic anemia (n=6), aplastic anemia (n=5) and other disorders (n=9). Disease-free survival in two years was observed in 27 (61.3%) of patients. Relapse occurred in 8 (18.1%) patients, whereas 9 (20.4%) patients died. The mortality was transplant-related in two cases, whereas it was due to progression of the underlying disease in 7 (15.9%) patients. Conclusion: As the stem cell transplantation has become widespread in Türkiye recently, its data are valuable. We found high incidence of mucositis and infection due to myeloablative regimens. The limitation of our study is the small number of patients included. Though, results obtained here are similar to those of national and international studies.

The prognostic significance of hematogones and CD34+ myeloblasts in bone marrow for adult B-cell lymphoblastic leukemia without minimal residual disease

This study was aimed to dissect the prognostic significances of hematogones and CD34+ myeloblasts in bone marrow for adult B-cell acute lymphoblastic leukemia(ALL) without minimal residual disease(MRD) after the induction chemotherapy cycle. A total of 113 ALL patients who have received standardized chemotherapy cycle were analyzed. Cases that were not remission after induction chemotherapy or have received stem cell transplantation were excluded. Flow cytometry was used to quantify the levels of hematogones and CD34+ myeloblasts in bone marrow aspirations, and the patients were grouped according to the levels of these two precursor cell types. The long-term relapse-free survival(RFS) and recovery of peripheral blood cells of each group after induction chemotherapy were compared. The results indicated that, after induction chemotherapy, patients with hematogones ≥0.1% have a significantly longer remission period than patients with hematogones <0.1% (p = 0.001). Meanwhile, the level of hematogones was positively associated with the recovery of both hemoglobin and platelet in peripheral blood, while CD34+ myeloblasts level is irrelevant to the recovery of Hb and PLT in peripheral blood, level of hematogones and long-term prognosis. This study confirmed hematogones level after induction chemotherapy can be used as a prognostic factor for ALL without MRD. It is more applicable for evaluation prognosis than CD34+ myeloblasts.

Outcomes after Stem Cell Transplant in Older Patients with Acute Myeloid Leukemia Treated with Venetoclax-Based Therapies

Outcomes after Stem Cell Transplant in Older Patients with Acute Myeloid Leukemia Treated with Venetoclax-Based Therapies

An Adjusted Treatment Comparison of Bortezomib/Cyclophosphamide /Dexamethasone and Bortezomib/Thalidomide/Dexamethasone from Real-World Data in Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant-Eligible

Introduction: For patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem-cell transplantation (ASCT), two standard of care (SoC) induction regimens are bortezomib/cyclophosphamide/dexamethasone (VCd) and bortezomib/thalidomide/dexamethasone (VTd), each followed by ASCT. While VCd and VTd are both treatment options according to international guidelines, treatment selection varies by country. Additionally, while some clinical studies have evaluated the efficacy and safety of these therapies, direct comparisons have been limited to response endpoints post-induction and post-transplant (Moreau P, et al. Blood. 2016;127[21]2569-2574; Cavo M, et al. Blood. 2014;124[21]197; Cavo M, et al. Leukemia. 2015;29[12]2429-31). Herein we describe real-world treatment patterns in the United States for patients with NDMM who are transplant-eligible, and report results from a matched adjusted comparison to evaluate real-world long-term efficacy (overall survival, OS) for VCd +ASCT versus VTd +ASCT. Methods: Data for the VCd and VTd real-world evidence (RWE) cohorts were identified from 3 US data sources collectively covering the period January 2000 to March 2017: the OPTUM™ Commercial Claims database, the OPTUM™ Integrated (CLAIMS+EMR) database, and the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked database. RWE data were from patients with an index MM diagnosis on or after 1 January 2007, medical prescription coverage in place at diagnosis, no prior malignancies in the 1-year period prior to index diagnosis, a 1-year look-back period prior to index diagnosis, received ≥1 line of therapy, and received stem cell transplantation with induction as frontline treatment. The Kaplan-Meier method and Cox proportional hazard model compared outcomes with and without adjustments for baseline characteristics (age, sex, renal impairment, and anemia) and induction treatment duration; comparisons were also conducted with inverse probability of treatment weighting (IPTW). Results: Analysis of RWE from the United States demonstrated that bortezomib (V)-based regimens were the most common induction treatment (together accounting for approximately 75% of therapies), with bortezomib/lenalidomide/dexamethasone (VRd) being the most common (31%). Use of VCd (13%) and VTd (5%) was limited. Comparisons were conducted for VCd (n = 135) and VTd (n = 51). Baseline characteristics were generally similar between groups, except for fewer male patients in the VCd group than the VTd group (57% vs 65%), and lower rates of renal impairment in the VCd group than the VTd group (29% vs 43%; Table 1). The naïve and adjusted comparisons of OS for VCd versus VTd therapy showed these treatments were not statistically different (adjusted hazard ratio, 1.180 [95%: 0.468-2.972]; P = 0.7260; Figure 1). The IPTW method generated similar results. Conclusions: Real-world data from the United States show that V-based induction regimens are the most commonly used for treatment of patients with NDMM who are transplant-eligible. Results from the naïve, adjusted, and IPTW comparisons all showed that OS was not significantly different for VCd + ASCT versus VTd + ASCT. Survival data for VTd from RWE are generally consistent with VTd data reported in the recent phase 3 CASSIOPEIA study, although OS data from CASSIOPEIA remain immature (Moreau P, et al. Lancet. 2019;394[10192]:29-38). Disclosures Cote: Janssen: Employment, Equity Ownership. Kampfenkel:Janssen: Employment, Equity Ownership. Nair:Janssen: Employment, Equity Ownership.

CPX-351 As First Intensive Therapy for Elderly Patients with AML

CPX-351 As First Intensive Therapy for Elderly Patients with AML

Utility of Flow Cytometry and Fluorescence in Situ Hybridization in Follow-up Monitoring of Multiple Myeloma

Introduction Diagnosis and follow-up monitoring of Multiple Myeloma (MM) requires documentation of (clonal) plasma cells using morphological bone marrow assessment and other ancillary studies including CD138 immunohistochemistry (IHC), flow cytometry (FC), and myeloma-specific fluorescence in situ hybridization (FISH). While IHC and FC have traditionally been shown to be the more sensitive methods for the assessment of residual disease, the detection rates of FISH have markedly increased with the recent use of magnetic cell sorting for CD138 cell enrichment. We, therefore, aimed to revisit the clinical utility of these ancillary studies in the diagnosis and follow-up of MM. Methods We retrospectively reviewed the reports of bone marrow biopsy specimens received for the initial diagnosis or follow-up assessment of MM from October 2015 to January 2019. All cases that had both FC and FISH performed were included in the analysis. Patient demographics, treatment history and the results of bone marrow evaluation were recorded. Results During the study period, we evaluated a total of 1,712 biopsy specimens from 464 MM patients (mean±SD age: 64.0±9.4 years; females 41.4%). Of these, 87 cases were submitted for initial diagnosis and 1,625 cases had already established MM and were being evaluated for post-treatment residual disease. For both initial diagnosis and follow-up cases, CD138+ IHC demonstrated highest plasma cell burden (mean: 49.1% and 4.6%, respectively) followed by morphological aspirate count (mean: 29.6% and 2.3%, respectively) and FC (mean: 10.9% and 1.8%, respectively). Both FC and FISH had comparable detection rates at the time of initial diagnosis (95.4% versus 97.7%, respectively) and for follow-up cases (28.6% versus 28.2%, respectively). The FC and FISH results were concordant in 97.7% of the initial diagnosis cases and 89.7% of follow-up cases. Discordant cases with positive FISH results and negative FC results included 2 (2.3%) initial diagnosis cases and 81 (5.0%) follow-up cases whereas those with negative FISH and positive FC results included 87 (5.3%) follow-up cases. In comparison with all concordant cases, the FISH positive, FC negative discordant cases were older in age, more likely to have received treatment with Daratumumab, and less likely to have received stem cell transplantation (p &lt;0.05) (Table 1). When compared to the FC and FISH positive concordant cases; both discordant groups had significantly lower plasma cell counts detected by the aspirate smear and CD138+ IHC (Figure 1). Among all FC positive cases, the discordant cases had lower FC detected plasma cell counts and were less likely to have aberrant CD56 expression as compared to the concordant cases (p &lt;0.05) (Table 2). Finally, among all FISH positive cases, the discordant cases were less likely to have 13q lesion and aneuploidy of chromosomes 5, 9, and 15 (p &lt;0.05) as compared to the concordant cases. Also, between these groups, the percentage of plasma cells with individual FISH aberrations was significantly lower among the discordant cases (Table 3). Conclusion Overall, FISH (with magnetic cell sorting) and FC have comparable detection rates at the initial diagnosis and follow-up assessment. Approximately 10% of the follow-up cases have discordant FISH and FC results where residual disease is detected by only one of these modalities. Also, the discordant cases have significantly lower plasma cell counts as compared to the FC and FISH positive concordant cases. Therefore, this study suggests that both FC and FISH are useful for the follow-up monitoring of MM, especially in the cases with low plasma cell burden. Finally, the higher frequency of Daratumumab treatment in FISH positive, FC negative discordant cases might suggest Daratumumab's potential interference with the residual disease detection by FC. Disclosures No relevant conflicts of interest to declare.

Effectiveness of Daratumumab in Combination with Lenalidomide and Dexamethasone (DRd) Vs. Common Standard-of-Care Regimens in Patients with Non-Transplant Newly Diagnosed Multiple Myeloma (NDMM)

Introduction: Daratumumab, a CD38-directed monoclonal antibody, in combination with lenalidomide and dexamethasone (D-Rd), recently received FDA approval for the treatment of patients with newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation (ASCT). FDA approval was based on results of the prespecified interim analysis of a pivotal phase III trial (MAIA) in which D-Rd was compared to Rd among patients with NDMM who were ineligible for ASCT. In the MAIA trial, D-Rd significantly reduced the risk of progression or death compared to Rd. However, no trials have compared D-Rd to other standard-of-care (SOC) regimens. The present study compared progression-free survival (PFS) of D-Rd from the MAIA trial database to common SOC regimens from the Flatiron Health EHR Database, a de-identified nationwide US database of records primarily from community-based oncology practices. Methods: Patient-level data were obtained from the MAIA trial and the Flatiron database. Patients in the MAIA trial were enrolled between March 2015 and January 2017. To be included in MAIA, patients had to be deemed ineligible for high-dose chemotherapy with ASCT due to either age (≥65 years) or presence of comorbidities, have Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, creatinine clearance ≥30mL/min, and adequate bone marrow reserve. In the Flatiron Database, patients had to be diagnosed with MM between January 2011 and April 2019, age ≥65 years at initiation of first line treatment (LOT1), could not have received stem cell transplant as part of LOT1, and met MAIA inclusion/exclusion criteria. Regimens received by fewer than 10% of patients in Flatiron were excluded due to sample size and statistical power considerations. Bortezomib-lenalidomide-dexamethasone (VRd), bortezomib-dexamethasone (Vd), and Rd were the most commonly used regimens in non-transplant NDMM patients, representing 67% of regimens used in this setting. Multiple imputation by chained equations was used to address missing data in Flatiron. Eligible Flatiron patients treated with VRd, Vd, or Rd as LOT1 were reweighted to resemble the MAIA trial population on measured baseline characteristics using propensity-score (PS) weighting. An anchored adjusted indirect treatment comparison (ITC) was performed to compare D-Rd to VRd and D-Rd to Vd, using a stratified Cox proportional hazards regression model with Rd as the common anchor across both data sources. The model calculates hazard ratios (HRs) for direct comparisons within MAIA (D-Rd vs Rd) and within Flatiron (VRd vs. Rd, Vd vs. Rd) to estimate the HRs indirectly for D-Rd vs. VRd and D-Rd vs. Vd. Results: After application of MAIA inclusion criteria and PS-reweighting, the Flatiron VRd, Rd, and Vd patients resembled the MAIA trial population on baseline patient demographics and clinical characteristics (Table 1). D-Rd statistically significantly reduced the risk of progression or death compared to Rd (HR=0.55; 95% CI, 0.41-0.72) based on the direct comparison with D-Rd using the MAIA trial data; D-Rd statistically significantly reduced the risk of progression or death compared to VRd (HR=0.66; 95% CI, 0.46-0.95) and Vd (HR=0.47; 95% CI, 0.33-0.67) based on the anchored ITC (Figure 1). Sensitivity analyses will be performed and updated analysis using longer follow-up data from the MAIA study will be presented at the meeting. Conclusion: This analysis demonstrated that D-Rd reduced the risk of progression or death compared to other SOCs VRd and Vd for patients with NDMM who are transplant-ineligible. In the absence of head-to-head trials, this type of patient-level analysis provides important information that can help optimize treatment for patients with NDMM who are transplant-ineligible. Disclosures Durie: Amgen, Celgene, Johnson &amp; Johnson, and Takeda: Consultancy. Kumar:Takeda: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Usmani:Amgen, Celgene, Janssen, Sanofi, Takeda: Speakers Bureau; Amgen Array Biopharma, Bristol-Myers Squibb, Celgene, Janssen, Merck, Pharmacyclics, Sanofi, Takeda: Other: Research Grant; Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, SkylineDX, Takeda: Other: Consultant/Advisor. Ammann:Janssen: Employment, Equity Ownership. Lam:Janssen: Employment, Equity Ownership. Kobos:Janssen: Employment. Maiese:Janssen: Employment, Equity Ownership. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Antibody-Associated Autoimmune Disease (AAD) in Children with Cancer in Immune Recovery Phase Following Cessation of Chemotherapy

(Introduction) Outcome of pediatric cancer has improved dramatically by intensive chemotherapy, surgical treatment, radiotherapy, and stem cell transplantation (SCT). In children with cancer, immune system is damaged during treatment. Autoimmune diseases such as autoimmune hemolytic anemia (AIHA) during immune reconstitution were observed as complication after intensive chemotherapy in our institute. Although most of them recovered with supportive treatment, immunosuppressive agents including steroid were needed in some patients. Thus, we defined this complication as antibody-associated autoimmune disease (AAD), and we examined AAD in pediatric patients following cessation of treatment. (Patients and Methods) We reviewed medical records of patients who received intensive chemotherapy in Department of Pediatrics, Hokkaido University Hospital. Between January 2010 and December 2018, 130 patients with hematological malignancies, 127 patients with malignant solid tumor, 120 patients with brain tumor were treated in our institute. All of these patients were included in this study. The diagnoses of AAD were made by clinical criteria, combined with laboratory evidence of a definitive antibody in the serum of patients such as positive Coombs test, antineutrophil antibodies, antiplatelet antibodies, and thyroid-stimulating antibodies. In this study, apparent clinical GVHD and AAD associated with SCT were excluded. (Results) Among the 377 patients, 10 patients (2.7%) developed AAD. AAD was observed as ITP in 5 patients, AIHA in 2 patients, Hashimoto's diseases, multiple sclerosis, and neutropenia with antineutrophil antibody in one patient each. AAD developed a median of 4.0 months (range 2-27months) after cessation of treatment. At onset of AAD, the mean CD4 positive cell counts was 397 /ul and the mean serum IgG was 789 mg/dl. Prednisolone was administered in 3 patients (AIHA and ITP) to treat AAD. The clinical symptoms of AAD regressed with supportive therapy only in the other patients. In 3 out of 5 patients who developed AAD with CD4 positive cell count over 500 /ul, autoimmune antibody in serum of the patients was detected continuously. On the other hand, in 5 patients who developed AAD with CD4 positive cell count below 500 /ul, both clinical symptoms and laboratory examinations regressed, synchronizing with the immune recovery. The mean duration of CD4 positive cell count &lt;500/ul was significantly longer in patients with AAD (n=10) compared with that in patients without AAD (n=45) (p=0.013, 11.0±7.2 months vs 5.6±5.3 months), and the mean duration of serum IgG &lt;500mg/dl was significantly longer in patients with AAD, compared to patients without AAD (p=0.002, 11.0±6.3 months vs 4.3±4.4 months). (Discussion and Conclusion) AAD was observed in immune recovery phase following cessation of chemotherapy, which mimicked immune reconstitution syndrome (IRS) after antiretroviral therapy in patients with HIV infection. It was reported that IRS was also observed in HIV-negative patients who were administered alemtuzumab, and in those who received stem cell transplantation. It was interesting that patients who had smaller number of CD4-positive cells at diagnosis of AAD had a faster recovery of the diseases in our study. We also speculate that AAD mimic autoimmune cytopenia such as ITP, AIHA, and autoimmune neutropenia in infancy because the diseases are caused by autoantibodies, occurring in immune-naive age, and they naturally recover in most cases although some patients need immunosuppressive treatment. Further studies are needed to clarify the pathogenesis of AAD in children. Disclosures No relevant conflicts of interest to declare.

Economic Burden of Emergency Room (ER) Visits and Hospitalizations Among Newly Diagnosed Multiple Myeloma (NDMM) Patients in the United States

Background: With the introduction of the Oncology Care Model, which aims to provide higher quality, more coordinated oncology care at the same or lower cost to Medicare, physician practices are increasingly being held accountable for performance and financial measures.1 Urgent care (emergency room [ER] visits and hospitalizations) is known to contribute a significant proportion of healthcare costs, and while there has been a focus on drug costs, little is known about the utilization or economic impact of urgent care among multiple myeloma (MM) patients. Objective: To identify the primary reasons and economic burden of ER visits and hospitalizations among newly diagnosed MM (NDMM) patients during first line of therapy (LOT1). Methods: Patients from the Optum Clinformatics Extended DataMart - Date of Death database (Optum DOD) with ≥1 medical or pharmacy claim for an NCCN listed MM treatment from 7/1/11 to 3/31/2018 (index date) were included if they had diagnosis code for MM (ICD9/10 code 203/C90) and ≥6-months continuous enrollment without MM treatment prior to index date. Patients were followed until death, end of eligibility, or end of study (9/30/2018), whichever occurred first. The top 20 most common primary diagnoses (PDx) for ER visits and for hospitalizations were identified separately for patients who received stem cell transplant (SCT) or not (nSCT) during LOT1. Total costs and per-patient-per-month (PPPM) costs of ER visits and hospitalizations for each PDx were reported. Results: Total 3,099 patients met inclusion criteria, including 2,761 (89.1%) nSCT and 338 (10.9%) SCT patients. nSCT patients were older than SCT patients (median nSCT=72 years vs SCT=62 years, p &lt; 0.0001). The most common treatment regimens among nSCT were bortezomib in combination with dexamethasone (dex) (34%) followed by lenalidomide in combination with dex (27.4%). The most common treatment regimen among SCT were bortezomib in combination with lenalidomide and dex (46%) followed by bortezomib in combination with chemotherapy (18.3%). Median duration of LOT1 was 5.1 months among all patients, with median 11.2 months among SCT vs 4.5 months among nSCT, p &lt; 0.0001). Among all patients, (Table 1) there was a total of 1,645 ER visits and 3,385 hospitalizations with a total cost of $3,729,208 and $56,751,758, respectively, and a PPPM cost of $146 and $2,220 for ER visits and hospitalizations, respectively. Among nSCT, there were 1,339 (81% of the total) ER visits and 2,776 (82% of the total) hospitalizations with a total cost of $3,063,727 and $39,763,095, respectively, and a PPPM cost of $151 and $1,955 for ER visits and hospitalizations, respectively. Among SCT, there were 306 (19% of the total) ER visits and 609 (18% of the total) hospitalizations, with a total cost of $665,481 and $16,988,663, respectively, and a PPPM cost of $127 and $3,253 for ER visits and hospitalizations, respectively. The most common PDx for hospitalizations among the entire cohort was 'MM, without mention of having achieved remission' with 769 hospitalizations for a total cost of $19,299,593 and a PPPM cost of $7,112. This same PDx was the most common among nSCT with 449 (58%) hospitalizations for a total cost of $7,551,282 and a PPPM cost of $9,292; as well as for SCT with 320 (42%) hospitalizations for a total cost of $11,748,760 and a PPPM cost of $4,435. This was also the most common PDx for ER visits among nSCT and SCT. For hospitalizations, the second most common PDx among the entire cohort and among nSCT was 'shortness of breath' while for SCT it was 'administration of antineoplastic chemotherapy'. The second most common PDx overall and for nSCT for ER visits was 'chest pain' and for SCT patients was 'musculoskeletal dysfunction (Segmental and somatic dysfunction of cervical region)'. Conclusions: In this analysis, NDMM patients experienced frequent ER visits and hospitalizations over a median of ~5 months for a total cost of more than $60 million, with most of the cost among nSCT patients. The most common PDx was related to MM. Even though some hospitalizations for the SCT patients may have been for the SCT procedure itself, the economic burden of urgent care for MM patients remains very high. Additional research to assess the impact of newer treatments on urgent care visits among NDMM, identify patients at high risk of urgent care visits may provide insight into the potential for developing cost-saving interventions to reduce the utilization of urgent care. Disclosures Maiese: Janssen: Employment, Equity Ownership. Zhu:Janssen Scientific Affairs, LLC: Other: contractor for Janssen. Wu:Janssen: Employment, Equity Ownership. Chen:Janssen: Employment, Equity Ownership. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Celgene: Consultancy; Cellectar: Research Funding; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding.

Efficacy and Safety of Carfilzomib-Lenalidomide-Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma: Pooled Analysis of 4 Single-Arm Studies

Efficacy and Safety of Carfilzomib-Lenalidomide-Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma: Pooled Analysis of 4 Single-Arm Studies

Treatment Patterns in Patients (pts) with Refractory/Relapsed Multiple Myeloma (RRMM) in Germany between 2016 and 2018

Treatment Patterns in Patients (pts) with Refractory/Relapsed Multiple Myeloma (RRMM) in Germany between 2016 and 2018

Effectiveness of Bosutinib in Chronic Myeloid Leukemia (CML) Who Have Received Multi Tyrosine Kinase Inhibitors (TKIs)

Effectiveness of Bosutinib in Chronic Myeloid Leukemia (CML) Who Have Received Multi Tyrosine Kinase Inhibitors (TKIs)

Frontline Treatment with Ibrutinib Plus Rituximab (IR) Followed By Short Course R-Hypercvad/MTX Is Extremely Potent and Safe in Patients (age ≤ 65 years) with Mantle Cell Lymphoma (MCL) - Results of Phase-II Window-1 Clinical Trial

Frontline Treatment with Ibrutinib Plus Rituximab (IR) Followed By Short Course R-Hypercvad/MTX Is Extremely Potent and Safe in Patients (age ≤ 65 years) with Mantle Cell Lymphoma (MCL) - Results of Phase-II Window-1 Clinical Trial

The Efficacy and Safety Profile of Ixazomib-Based Regimens in Patients with Relapsed/Refractory Multiple Myeloma in Routine Clinical Practice: Real World Data from a Multi-Center Study in China

J Li, L Bao, ZJ Xia and KY Ding contributed equally to this study. Background: Based on the promising results shown in the phase 3 trial (TOURMALINE-MM1, NCT01564537) and the China Continuation Study of MM1, the oral proteasome inhibitor (PI) ixazomib (ixa) was approved in China in April of 2018, in combination with lenalidomide (len) and dexamethasone (dex) (IRd), for patients (pts) with relapsed/refractory multiple myeloma (RRMM). Data on the efficacy and safety of ixa-based therapy in Chinese pts with MM in real-life practice is rather limited. A large national, multi-center, real-world study involving 14 centers from different areas of China was performed to investigate the current status of ixa usage in China and to evaluate the efficacy and safety in routine clinical practice. A total of 246 ixa-treated MM pts was enrolled, with 163 (66.3%) RRMM, 60 (24.4%) newly diagnosed MM and 23 (9.4%) pts received ixa as maintenance. Herein, we reported the data of RRMM in this study. Methods: Medical records, including demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs) and survival, of ixa-treated (at least one cycle completed with response evaluation result) RRMM pts were analyzed. Results: A total of 149 evaluable pts (out of 163 RRMM pts) treated from April 2018, to July 2019 were included in analysis. Baseline features and prior treatment are summarized in Table 1. Patients were categorized into MM1 trial-eligible/-ineligible groups according to the inclusion and exclusion criteria of MM1 study. Median age was 62 years (range 33 - 87) with 52 (34.9%) ≥65 years. Most pts (75.2%) had ISS stage II-III disease. High-risk cytogenetic abnormalities (including del 17p, t (4;14), and/or t (14;16)) were detected in 19 patients (21.1%, among 90 patients with FISH results). Fifty-two (34.9%) pts had a ECOG PS ≥2. Overall, ixa-based regimens were used as the 2nd/3rd/4th/≥5th-line therapy in 29.7%, 33.1%, 16.2% and 17.4% of the pts, respectively. Prior treatment included bortezomib (91.9%), len (52.0%) and thalidomide (58.8%). More than half pts (54.7%) were refractory to previous bortezomib treatment, and 32.2% pts were len-refractory. MM-1 trial-ineligible pts had more advanced ISS stage, higher ECOG PS, more severe anemia, more lines of prior therapy and more refractory diseases. Treatment, outcome and survival were listed in Table 2. Ixa-based regimens included IRd in 70 (47.0%) patients, ixa-dex (Id) in 31 (20.8%) patients and Id plus chemotherapeutics/other agents (44, 29.5%; including cyclophosphamide in 14 pts, thalidomide in 12 pts, adriamycin in 6 pts, melphalan in 5 pts and daratumumab in 3 pts) in 20 (33.3%). (Table 2). One patient received stem cell transplantation (SCT) during follow-up. The best confirmed ORR (≥PR) for all 149 patients was 53.7% (80/149), including 28.2% of patients with ≥VGPR and 7.4% with a CR, with a median time to response of 41.5 days. Surprisingly, ixa-based regimens demonstrated efficacy in pts with PI/len refractory diseases, with an ORR and ≥VGPR rate of 44.4% and 19.9% for PI-refractory pts, and an ORR and ≥VGPR rate of 30.6% and 12.2% for len-refractory pts. Pts eligible for MM1 study shown comparable ORR (76.7%) with that reported in MM1 (ORR 78%). No significant difference in response between different ixa-based regimens was observed. The median PFS of the whole cohort, pts with standard/high cytogenetic risks, pts refractory to bortezomib/len and pts eligible/ineligible for MM1 trial was 8.2, 8.2, 6.8, 6.7, 5.9months, not reached and 6.6months respectively. The median overall survival (OS) of the whole cohort and every subgroup was not reached. Adverse events (AEs) of grade 3/4, reported in 40 (27.2%) patients, included 10.1% thrombocytopenia, 5.4% anemia, 3.4% diarrhea and 6.0% pneumonia. Only 3 (2.01%) pts had a grade 3/4 peripheral neuropathy during follow-up. Discussion and conclusion: Our results show that ixa-based therapy demonstrated good efficacy with limited toxicity for pts with RRMM in real-life clinical practice. Moreover, in pts with PIs- or len- refractory diseases, ixa-based therapy still showed acceptable effectiveness (ORR: 44.4% and 30.6%; mPFS: 6.7 months and 5.9 months). Although 70.5% pts in our real-life cohort were ineligible for MM1 trial, the efficacy and safety profile is similar to that reported in MM1 China Continuation Study. Ixa-based therapy is a reasonable choice for Chinese RRMM pts. Disclosures No relevant conflicts of interest to declare.

PCN514 REAL WORLD TREATMENT PATHWAYS OF DIFFUSE LARGE B-CELL LYMPHOMA IN GERMAN CLAIMS DATA

Real world sick funds data in Germany were used to reveal the treatment patterns for Diffuse Large B-cell Lymphoma (DLBCL) and to identify unmet medical needs. In two independent cohorts of German claims data 819 and 189 DLBCL patients were identified and diagnoses, hospitalization, medication and health costs were analyzed for at least two consecutive years between 2013 and 2016. In the first [second] cohort, mean age of DLBCL patients was 60.3 [66.5] years, with two peaks at 50-54 and 70-74 years. Total annual health care costs for DLBCL patients ranged from 25,000 to 60,000 EUR versus 1,259 EUR in healthy insured. Per year, mean 3.2 [3.5] hospitalizations with an average of 31.5 [34.5] hospital days were observed. During the observation period less than half of the DLBCL patients received oncological treatment and only few patients received stem cell transplantation or radiation. Most frequent pharmacological first line treatments were Rituximab (RTX) + CHOP (57%, [56%]) and RTX in combination with Bendamustine (8%, [7%]). In both analyses consistently 84% of patients did not receive further therapies after a first line DLBCL treatment during the limited observation period. Despite limitations in sick fund claims analyses, these databases are a reasonable source for real world evidence (RWE) of rare diseases. Both cohorts were well in agreement and revealed standard treatment pathways consistent with the German treatment guidelines. All DLBCL patients frequently required hospitalization and generated significant costs. A high unmet medical need exists for treatments other than palliative care, especially for a tolerable and effective outpatient therapy in elderly relapsed / refractory DLBCL patients.

Treatment Journeys of Patients With Newly Diagnosed Multiple Myeloma (NDMM): Results From The Connect MM Registry

Sankey plots were generated to illustrate the heterogeneity of treatment sequences and transitions over time in real-world patients from the Connect Multiple Myeloma (MM) Registry. Plots identified immunomodulatory agents and proteasome inhibitors as the mainstays of treatment for patients who did or did not receive stem cell transplant. More patients received stem cell transplant (shown above) and continued to second-line treatment, which highlights the need to choose optimal first-line regimens – particularly for patients without a transplant intent.

2059 A Case of Hepatosplenic T-cell Lymphoma in a Patient on Vedolizumab for Crohn’s Disease

INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL) is a rare malignancy, most commonly affecting young males with often fatal prognosis. In patients with inflammatory bowel disease (IBD), HSTCL has been associated with thiopurine analog and tumor necrosis factor (TNF)-α inhibitor therapy; particularly when used in combination, the risk increases up to 4 fold. Development of HSTCL has not been reported in association with vedolizumab. CASE DESCRIPTION/METHODS: A 22-year-old male with severe, stricturing colonic Crohn’s disease of 10 years duration, on vedolizumab monotherapy every 4 weeks for 15 months, was incidentally noted to be pancytopenic in October 2016 and subsequently diagnosed with HSTCL by bone marrow biopsy. Previous IBD therapies included mesalamine, azathioprine, infliximab, adalimumab, intravenous immunoglobulin (IVIG), budesonide, certolizumab pegol and most recently 6 mercaptopurine (6-MP). The 6-MP was discontinued 1 year prior to HSTCL diagnosis. He achieved remission with chemotherapy, followed by autologous stem-cell transplant in September 2017. Unfortunately his disease relapsed only a few months later. He achieved a second remission with salvage chemotherapy, and proceeded to allogeneic bone marrow transplant in April 2018. Since diagnosis of HSTCL, he did not receive any therapy for Crohn’s disease and has been asymptomatic from his IBD. Colonoscopy demonstrated complete endoscopic and histologic remission as well. On last bone marrow biopsy, over 200 days post-transplant, there was no evidence of HSTCL relapse 24 months following HSTCL diagnosis. DISCUSSION: Fortunately, our case had a favorable outcome compared to those reported in the literature with a median overall survival of 10 months, and up to 17 months in patients who receive stem cell transplant. In addition, following stem cell transplant, our patient achieved cure of his Crohn’s disease. A recent review of patients with immunoregulatory disorders who developed HSTCL noted that 56% of patients were treated with TNF-α inhibitors versus 89% with immunomodulators, indicating that the latter pose higher risk. To our knowledge, there have not been reports of HSTCL associated with vedolizumab use nor is there a known mechanism by which vedolizumab could cause HSTCL. In our case, TNF-α inhibitor was stopped 5 years prior and thiopurine analog 1 year prior to diagnosis, raising the question as to how long the risk of HSTCL remains elevated after cessation of such agents.

Clinically significant delay in engraftment with day -1 melphalan prior to stem cell infusion in myeloma patients receiving stem cell transplant.

Although single agent melphalan is considered the standard conditioning regimen for autologous transplant in myeloma, the timing of melphalan administration is less standardized with limited evidence on optimal timing of infusion.

Current Status of the Management of Mendelian Susceptibility to Mycobacterial Disease in Mainland China.

Although many studies have investigated Mendelian susceptibility to mycobacterial disease (MSMD) worldwide, there is no report of the long-term clinical management and prognosis for MSMD in China. This is a cohort study from January 2000 to June 2018. Three hundred and twenty-four patients with bacillus Calmette-Guérin (BCG) infection were diagnosed during this period, and those with MSMD diagnosed by genetic and functional experiments were enrolled in the study. The clinical and genetic characteristics and management of these MSMD patients were summarized. Thirty patients diagnosed with MSMD were followed up. The age at the follow-up end point ranged from 5 to 173months. Among the patients, IL12RB1 mutations were identified in 22, IFNGR1 mutations in 5, STAT1 mutations in 2, and IFNGR2 mutation in 1. The medium age at onset was 3months. BCG infection involved multiple organs, including regional infection (8/30; 26.7%) or distant or disseminated infection (22/30; 73.3%). Ten percent (30/324) of patients with BCG infection had a confirmed MSMD diagnosis. Protein expression of IL12RB1 or IFNGR1 was decreased in all patients with IL12RB1 or IFNGR1 mutation, respectively, as indicated by flow cytometry. In addition, 77.8% of patients received rhIFN-γ treatment, which can improve the prognosis of patients with IL12RB1 deficiency. Two patients received stem cell transplantation. Twenty-five patients remained alive at the time of publication. MSMD is an important cause of BCG infection. Flow cytometric detection of IL12RB1 and IFNGR1 expression is very useful for rapid MSMD diagnosis. rhIFN-γ therapy is effective in patients with MSMD, particularly improving prognosis in those with IL12RB1 deficiency.