Reasons For Early Discontinuation Research Articles

Outcomes in Acute Lymphoid Leukemia Patients with Incomplete Hyper-CVAD Cycles

Introduction: Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) is a commonly used regimen in acute lymphoblastic leukemia (ALL) for a total of 4 A/B intensive courses. This regimen is often limited due to multiple complications including organ dysfunction and medication toxicities along with high rates of relapse or disease progression. Prior studies have indicated five-year overall survival (OS) of 39% with severe prolonged myelosuppression being a common complication. In one study 6% of patients died during induction therapy. Here we provide clinical outcomes of non-transplanted patients with ALL receiving hyper-CVAD regimen in our tertiary referral center. We assessed overall survival, mortality rates, and complications during induction therapy with hyper-CVAD in our cohort of adult patients. Methods: We conducted a comprehensive, retrospective study at our center, evaluating outcomes of non-transplant eligible ALL patients treated from February 2003 to October 2022. We excluded patients without all available diagnostic information, and those who underwent allogeneic stem cell transplantation (SCT). We classified the patient based on their BCR - ABL1 gene status. Groups were subcategorized by highest cycle of Hyper-CVAD completion, with reason for cessation (medication toxicity/organ dysfunction, lost to follow up, progressive disease/relapse) elicited for those who did not complete all treatment cycles. Overall survival was analyzed using T-Test, ANOVA and Bartlett's test. Statistics are descriptive and our institutional review board approved this retrospective study. Results: We report outcomes of 43 ALL patients who did not undergo SCT. Median age at diagnosis was 52 years (range of 18-71 years). 33/43 (76.7%) patients received Hyper-CVAD regimen. 2/33 (6.1%) completed the entire course through 4B. 12 (36.3%) out of 33 patients received less than cycle 3b; 21/33 (63.6%) received at least cycle 3b. 2/6 (33.3%) completed up to cycle 1B, 2/11 (18.2%) completed up to cycle 2B, 13/25 (52%) completed up to cycle 3B, and 2/33 (6.1%) completed up to cycle 4B. 12/33 (36.4%) of patients were not able to complete more than cycle 3A due to organ dysfunction and intolerance, being lost to follow up, progressive disease or relapse, or participation in a trial. For the patients who received less than cycle 3b, the reasons for early discontinuation were: organ dysfunction 6/12 (50%), progressive disease or relapse 3/12 (25%), lost to follow up 2/12 (16.7%), or participation in a trial 1/12 (8.3%). Median overall survival (OS) for patients who received up to cycle 3A was 640 days compared to a median of 711 days for those who received at least cycle 3B. Median OS for patients who received up to cycle 3A in the Ph-negative group was 21.0 months and 23.1 months in the Ph-positive group. Median OS for patients who received at least 3B in the Ph-negative group was 20.9 months and 23.9 months in the Ph-positive group. Conclusion: Hyper-CVAD is the mainstay of ALL treatment. Induction chemotherapy in ALL is commonly associated with myelosuppression and documented infections (sepsis, pneumonia, port infection). Other significant side effects include neurotoxicity, liver and kidney failure. Induction chemotherapy in some patients was a limiting factor in completing therapy. We report the different reasons for terminating the treatment course to be: organ dysfunction or intolerance such as liver injury, neutropenic fever, septicemia, subarachnoid hemorrhage, renal failure, congestive heart failure, respiratory failure requiring intubation, port infection, cytokine release syndrome, and neurotoxicity. Median OS was longer in the Ph positive subgroup but the mortality rates for this subtype was not different between the patients who received up to cycle 3A verses those that received at least cycle 3B. In this study, our descriptive analysis did not show a clinically meaningful difference in survival in patients who did not finish the total induction course. A limitation of this study was not analyzing intrathecal prophylaxis as involvement of the central nervous system is a major clinical concern. Herein, we suggest a personalized approach in treating ALL patients considering infection risk, disease cytogenetic risk and depth of response to help adjusting the number of induction cycles based on the mentioned risk factors.

Continuation Rates of the Etonogestrel Implant and Factors Associated With Early Discontinuation.

The etonogestrel implant is generally consideredaneffective, three-year, long-acting reversible contraceptive device. Previous research, such as the landmark CHOICE study, has reported a one-year continuation rate of 72% to 84%, however, in a real-world setting these rates may be significantly lower. To study etonogestrel implant continuation rates and factors associated with early discontinuation in a specific clinical setting. Single-center, retrospective cohort study of patients who received the etonogestrel implant between January 1, 2015, and December 31, 2017, at several practices at an academic community hospital network. Records were reviewed up to three years after implant insertion to determine continuation rates (oneto threeyears), early discontinuation rates (≤12 months), and reasons for early discontinuation. A sample size calculation was performed to guide a subanalysis of side effects. A total of 774 patients underwent etonogestrel insertion during the study period.The one-year continuation rate was lower than that of the CHOICE study (62% vs. 83%, P <0.001). A subanalysis (n=216) revealed that a majority (82%, n=177) of patients reported side effects. Side effects were more common in patients with early discontinuation compared with patients who continued use longer than one year (93% vs. 71%, P <0.001). The most common side effect, abnormal uterine bleeding, was not significantly associated with early discontinuation. A significant association (P=0.02) was found between early discontinuation and neurologic/psychiatric complaints. The one-year continuation rate of the etonogestrel implant inourpopulation is significantly lower than the value reported by CHOICE. Implant side effects are common and significantly affect rates of discontinuation. Our data suggest there is an opportunity for education and counseling for individuals opting for this method of long-acting contraception.

Utilization of metastatic hormone sensitive prostate cancer (mHSPC) treatment in a community oncology practice setting.

86 Background: Treatment options for mHSPC have continued to evolve. While androgen deprivation therapy (ADT) has been the backbone treatment, more recently early use of docetaxel and/or novel androgen receptor inhibitors (nARIs) has demonstrated improved clinical outcomes. This study assessed real-world treatment among mHSPC patients who received at least one line of therapy (LoT). Methods: A retrospective observational study utilizing de-identified health records from five Cancer Treatment Centers of America (CTCA) included patients with metastatic prostate cancer who were treated with ADT, docetaxel or nARIs at CTCA for 6+ months between 1/2015-3/2021. Treatment patterns were observed from first LoT to metastatic castration resistance, death, or lost-to-follow-up until 3/2022. LoT was defined as first to last date of active drug therapy, not including long-term hormone agonists. First LoT was defined as initial regimen with no new drugs added 30+ days after start date. Patient characteristics, proportion and duration of each LoT, and reasons for early discontinuation were gathered using structured data elements and chart abstraction. Results: The characteristics of the 523 patients in this study were as follows: mean (SD) age 62 (8) years, 60% white and 33% black, 53% with commercial insurance, 75% with ECOG 0-1, and 65% with bone metastasis at diagnosis. Median follow-up time was 2.9 years. The most common LoT 1 regimen was either ADT alone or ADT with first generation androgen receptor inhibitors (FGARI) (table below). 46% received a second and 15% received a third LoT. Mean (SD) duration of first and second active LoTs were 12 (11.8) and 10 (11.1) months, respectively. Among the 65% and 78% patients who discontinued therapy in LoT 1 and 2, respectively, the majority discontinued due to progression of disease (35% LoT 1 and 53% LoT 2) followed by patient choice (23% LoT 1 and 18% LoT 2). Conclusions: Despite recommendations from guidelines on early intensification of therapy in mHSPC, in this contemporary cohort we find that most patients received either ADT alone or ADT ± FGARI in LoT 1 while chemotherapy and nARIs were initiated predominantly in later lines. Most patients discontinued LoT 1 due to disease progression which may suggest undertreatment and need for improved outcomes. Further studies are needed to assess the factors associated with non-intensification of treatments. [Table: see text]

1795. Evaluation of Appropriate Daptomycin Usage in an Academic Medical Center

Abstract Background The usage of daptomycin at our institution has steadily increased, with a threefold increase from Jan 2020 to Jan 2022 according to Days of Therapy Data. The increased usage prompted this study to determine whether daptomycin use at our institution is appropriately indicated and supervised by the infection disease service. Methods We conducted a retrospective descriptive study on 74 patients who were selected randomly from a total of 234 pts who received daptomycin at our facility in Northwest Louisiana over the past two years. We studied the patient's age and gender, type of infection, indications, empiric versus targeted therapy, culture results, infectious disease consultation, and reason for early discontinuation. Results Seventy-four pts were included in the analysis. The median age was 53.50 (22-90 yrs), and 47 pts (63.5%) were male. The most common infections were bone and joint (37, 50.7%), followed by bacteremia (22, 30.1%), followed by infective endocarditis (4, 5.5%). The infectious disease service was consulted before administration of daptomycin in 87.3% (62 patients). In 70.3% (52 patients), daptomycin was used as targeted therapy. MRSA was the most common bacteria for which daptomycin was used (29, 42.6%), followed by Enterococcus faecalis (10, 14.7%) and Coagulase-negative staphylococcus (8, 11.8%). Fifty-five pts (74.3%) received vancomycin before switching to daptomycin. The most common indications was MRSA with vancomycin MIC ≥ 2 mcg/ml (25, 33.8%), followed by as an alternative to vancomycin in acute renal failure (14, 18.9%), followed by clinical or/and microbiological failure on the previous antibiotic regimen (10, 13.5%). Thirty-six pts (48.6%) completed their course, 20 (27%) pts had early discontinuation, 11 pts (14.9%) were lost to follow-up, 4 pts (5.4%) were still on daptomycin at the time of data collection, and 3 pts (4.1%) died during hospitalization. The most common cause of early discontinuation was the culture growing pathogen necessitating discontinuation of daptomycin (7 patients, 35%), followed by insurance issues that account for 15%. Conclusion Most daptomycin usage in our institution was wisely indicated under the supervision of the infectious disease service and was primarily used as targeted therapy. Disclosures All Authors: No reported disclosures.

Real World Outcomes of Brentuximab Vedotin Maintenance after Autologous Stem Cell Transplant in Relapsed/Refractory Classical Hodgkin Lymphoma: An Time-Variable Analysis of the Effect of Dose on Progression Free Survival

Background: In the AETHERA trial, brentuximab vedotin (BV) maintenance after autologous stem cell transplant (ASCT) in patients (pts) with high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL) demonstrated an improvement in 2-year progression free survival (PFS) over placebo [Moskowitz 2015]. However, in clinical practice, pts are rarely able to complete all 16 cycles of BV at full dose due to toxicity. The aim of this retrospective, multicenter study was to investigate the effect of the cumulative maintenance BV dose on 2-year PFS in pts with high-risk r/r cHL. In an earlier analysis of this study, we found that 50-75% of the total cumulative BV dose attains a similar PFS advantage as >75% dose [Wagner 2022], we now report further findings with additional pts and a modified statistical analysis where total cumulative dose was treated as a time varying exposure. Methods: Individual patient data were collected from those who received at least one cycle of BV maintenance after ASCT from 13 institutions across the United States. Pts were required to have at least one high-risk disease feature as defined in AETHERA: primary refractory disease (PRD), extra-nodal disease (END), or relapse < 12 months from the end of frontline therapy (RL <12). Pts were split in to 3 different cohorts based on total cumulative dose of BV maintenance. Cohort 1 (C1) included those who received > 75% of the planned total cumulative dose, cohort 2 (C2) included those who received 51 - 75%, and cohort 3 (C3) included those who received ≤ 50%. In order to avoid bias from conditioning on future exposure, the total cumulative dose was treated as a time varying exposure. We linearly interpolated when each dose was administered based on when the first and last dose of BV maintenance were administered. Pts were excluded if we did not have a date of first or last BV exposure. Adverse events were defined using CTCAE v. 5 criteria. A multivariate analysis was performed assessing the effect of total cumulative BV dose, RL <12, PRD, achieving less than a CR prior to ASCT, receiving two or more salvage therapies and prior BV exposure on 2-year PFS. Descriptive statistics were utilized, and survival outcomes were estimated using Kaplan-Meier. Results: A total of 123 pts were screened for inclusion; 5 did not have documented dates of first or last BV administration and were excluded, for a total of 118 evaluable pts. The median age was 36 (27 - 42) years, 53% being male, and the majority (95%) receiving ABVD as frontline therapy. High risk features were as follows: 50% of pts had PRD, 29% had RL<12 and the remaining 21% relapsed ≥ 12 months after initial therapy with 39% of total pts having END. Twenty-three percent had more than one line of salvage before ASCT. The majority of pts achieved a CR (65%) prior to ASCT and half (49%) had BV exposure prior to ASCT (majority during salvage) (Table 1). The median follow up for the entire cohort was 2.96 years. The median number of BV maintenance cycles completed was 12 with the majority (69/118 = 59%) of pts discontinuing BV maintenance prior to completing all 16 cycles. Reasons for early discontinuation were as follows: 45 for toxicity, 10 for progression, 8 for patient preference, 2 for cost and 4 for other reasons. Forty-eight pts (41%) had a dose-reduction prior to discontinuation or completion of maintenance. Only 14% of pts (16/118) received the full cumulative dose of BV. One patient continued past 16 cycles and received a total of 25 cycles. Grade ≥3 adverse events for neuropathy, neutropenia, and infections were 17%, 7%, and 4% respectively. The 2-year PFS was 89.2% for C1, 86.2% for C2, and 77.9% for C3 (p = 0.70, Figure 1). No variables were significant in the multivariate analysis for PFS (Table 1). Conclusions: The 2-year PFS was robust regardless of cumulative dose of BV maintenance. The 2-year PFS was superior for all groups compared to the original AETHERA trial, which had a 2-year PFS of 65% [Moskowitz 2015]. This difference could be due to higher rates of CR achieved with novel salvage agents prior to ASCT in this population versus the pre-ASCT CR reported in the AETHERA trial (37-38%) [Moskowitz 2015]. PFS was not affected by prior BV exposure during salvage therapy. These data are reassuring for pts who require dose reductions or discontinuation to manage toxicity and suggest that the PFS advantage may still be attained. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Early discontinuation of abiraterone acetate/prednisone (AA/P) in localized prostate cancer.

e17003 Background: Data from STAMPEDE trial supporting systemic therapy intensification with long course AA/P was first presented in 2017. Overall survival benefit was confirmed in 2021. Our institution proceeded with early adoption of addition of 24 months of AA/P to ADT and radiotherapy (RT) in patients with high-risk localized or regional prostate cancer in 2017. In STAMPEDE, only 17% patients discontinued AA/P prior to completion of planned course. Outside of a clinical trial, whether patients adhere to this intense combination therapy that is associated with toxicities and expense is unknown. We hypothesized that adherence to long course AA/P in real-world practice in definitively treated prostate cancer would be poor. Methods: We performed a retrospective study for patients with clinically localized prostate cancer treated with AA/P combined with standard ADT and RT who had at least 6 months of follow-up data. Primary endpoint was rate of early discontinuation (prior to the 24mo) of AA/P. Secondary outcomes included rates of RT completion and disease recurrence and toxicity of intensive therapy. Reasons for early discontinuation were analyzed. Fisher's Exact, Chi-square analysis and Mann-Whitney tests were used to compare variables. SAS 9.4 was used for statistical analysis. Results: We identified 77 patients who met inclusion criteria, including 2 (2%) with high-risk, 30 (39%) with very high-risk, 19 (25%) with regional risk and 26 (34%) with locally recurrent disease after prostatectomy. AA/P was discontinued in 29 (38%) patients prior to completion of 24mo. Among those with early discontinuation, median duration of AA/P was 12.1 mo [0.1-21.7] and median duration of ADT was 17 mo[3.5-32.2]. Common reasons for early AA/P discontinuation included refractory hypokalemia (n = 4), diarrhea (n = 3), heart failure and fluid retention (n = 2 each) and quality of life deterioration (n = 8). Other reasons included hepatotoxicity, arrhythmia, osteoporotic fracture and financial toxicity (n = 1 each). All patients completed definitive RT. Only 1 of 77 patients had disease recurrence and had discontinued AA/P after 14 mo. A statistically significant association between age at diagnosis and treatment completion was noted(p = 0.01); each 1-year increase in age was associated with 9.4% decrease in odds of completing AA/P. Median age at diagnosis in those completing vs not completing AA/P was 65 vs 71 years. Conclusions: Very high rates of early discontinuation of AA/P were observed among patients with localized prostate cancer receiving definitive RT. Patients were less tolerant of toxicity in adjuvant setting compared to in a clinical trial or advanced disease. Shorter durations of AA/P appeared more acceptable but whether similar benefit is derived with a truncated course of AA/P is unknown. Future studies need to explore an optimal duration of AA/P that will reduce toxicity without compromising survival benefit.

CPX-351 for Acute Myeloid Leukaemia: Real World Results Are Comparable to Trial Outcomes and Exceeds Them in Non-Adverse Risk Patients- a Multicentre Experience from West Midlands Hospitals on Behalf of West Midlands Research Consortium ( WMRC) UK

Patients with secondary AML or MDS derived AML have poor outcomes compared to de-novo AML. The benefits of intensive chemotherapy without anticipated transplant consolidation have been previously doubted. Outcomes in USA trial centres have not often been closely replicable in real world settings. From November 2018 CPX-351 has been available in the UK for secondary AML, therapy related AML, AML with MDS related Karyotype (AML-MRC) and licensed but not funded for AML with myelodysplastic related changes.ObjectivesHere we report our experience specifically on patient outcomes and toxicity across 5 Hospitals in West Midlands, UKMethodsPatients receiving CPX 351 outcomes were evaluated retrospectively from 2018 to 2021. Baseline genetics, CPX 351 indications, patient's comorbidities, overall survival, remission status, number of cycles delivered, early mortality, reasons for early discontinuation, intensive care admission and time for neutrophil recovery (>0.5) was recorded. Time-to-event outcomes reported here are from a data cut on 01-06-21ResultsIn a total cohort of 57 patients baseline characteristics are shown on table 1 and compared with the original trial CPX-351 group. Median follow up was 376 days (range 21 to 1248 days).The mean age was 63, 17 patients were under 60, 31 males and 26 females.The most common indication for CPX-351 was AML with antecedent MDS/MPN 51% (N=29), therapy related 14% (N=8), MDS related karyotype (AML-MRC) 19% (N=11) and 16% (N=9) other patients.Mean Charleston co-morbidity score was 2.7 (range 0-6), 10.5% (N=6) had previous non myeloid malignancies, 8.7% (N=5) had prior ischaemic heart disease, only 3.5% (N=2) had ejection fractions under 50%.The most common mutations were TP53 21% (N=12), ASXL1 15.7% (N=9), TET2 15.7% (N=9), IDH2 10.5% (N=6), RUNX1 10.5% (N=6), SRSF2 7% (N=4), JAK2 3.5% (N=2), FLT3 5% (N=3), NPM1 5%(N=3) and IDH1 5% (N=3).MRC cytogenetic risk was adverse in 19 patients (33%), intermediate in 35 patients (61%) and favourable in 3 patients (5%).30 patients (53%) had adverse European Leukaemia Network classification, 17 (30%) had intermediate and 10 (17%) had favourable.30-day mortality was 3/57 (5%), 60-day mortality was 6 (10.5%) comparable to the 5.9% and 10.6% rates for the original trial. 9% or 5/57 patients were admitted to ITU with 2 survivors beyond 60 days. Neutropenic fever requiring antibiotics was 100% whereas only 5/57 (9%) had radiological evidence of fungal infection. Only one patient died from COVID 19.The mean time to neutrophil recovery was 35 days with a range of 12 to 84 days.29 patients completed 1 cycle, 25 completed 2 cycles, only 3 completed 3 cycles. The reasons for stopping were death, refractory disease, drop in performance status, alternative chemotherapy chosen or moving to transplantation (39%).Composite remission rate including CRi was 61% 36/57, adverse ELN group demonstrated 50% 15/30, intermediate 76% 13/17 and favourable 80% 8/10. Mutated P53 was associated with a 50% 6/12 rate whereas in wild type P53 the remission rate was 60% 30/45.Overall median survival from diagnosis was 429 days [95% CI 274 to 788 days]. To compare with the original trial, we removed the under 60s and those with less than 1 year follow up, in this cohort of 30 patients the median survival was 289 days (9.5 months) with 95% CI of 255 to 476 days.P53 mutated patients had an estimated median survival of 257 days versus wild type p53 with 524 days hazard ratio of 2.418 (CI 1.077 to 5.248) with p value of 0.032. Median survival for ELN groups was 373 days (adverse), 413 days (intermediate) and not reached for favourable.Of the 36 patients who achieved a remission, 22 went on to receive an allogenic transplant with follow from 254 to 1248 days, median survival estimated 706 days (95% CI 429-not reached). Patients in remission who haven't received a transplant have a similar estimated survival of 788 days (305-not reached) pending longer follow up.ConclusionThis is the first UK multicentre analysis to show comparable results to the landmark trial (median survival 9.5 months in equivalent cases). The improved overall remission rate 61% versus the 47% in the trial and the longer median survival 14 months versus 9.5 months in the trial is expected given the younger age and increase in favourable risk genetics. This study therefore supplies further data of CPX-351 efficacy in younger patients not included in the original studies and may now be used as a standard comparator arm. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of cure rate in patients with hepatitis C virus completing shortened courses of treatment

BackgroundGuidelines recommend treatment with direct-acting antivirals for a minimum duration of 8 weeks in all patients with hepatitis C virus. Minimizing treatment duration is desirable because of decreased cost and increased adherence. Studies with treatment durations of less than 8 weeks have conflicting data. ObjectiveThe purpose of this study was to evaluate the clinical efficacy of hepatitis C treatment in patients who did not complete the guideline-recommended duration of therapy. MethodsThis was a retrospective, observational case series of patients with hepatitis C virus treated with 7 weeks or less of direct-acting antivirals between November 1, 2017 and July 31, 2019 at a large, academic medical center. The primary end point was cure, defined as sustained virologic response at 12 weeks after the end of treatment. Secondary end points included average duration of therapy, direct-acting antiviral used, and reason for early discontinuation. ResultsOf the 472 patients treated, 13 met criteria for inclusion. Sustained virologic response was achieved in 61.5% of the patients. Two patients (15.3%) were not cured, and 3 patients (23.1%) were lost to follow-up. Median duration of therapy was 4 weeks. All patients who received at least 4 weeks of therapy and remained in care were cured. ConclusionIn situations in which patients inadvertently stop hepatitis C treatment early, there is still the possibility of cure. Further studies are needed to determine which patient population may benefit from a shorter duration of therapy.

A Phase II Study Demonstrates No Feasibility of Adjuvant Treatment with Six Cycles of S-1 and Oxaliplatin in Resectable Esophageal Adenocarcinoma, with ERCC1 as Biomarker for Response to SOX.

Simple SummaryNeoadjuvant chemoradiotherapy followed by surgery is currently standard of care in esophageal adenocarcinoma. However, prognosis remains dismal. The aim of our study was to assess the feasibility of administering six cycles of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy and esophagectomy. Although six cycles of adjuvant S-1 and oxaliplatin were not feasible in pretreated patients, mainly due to toxicity, efficacy results were promising compared to a propensity-score matched cohort. Exploratory biomarker analyses demonstrated potential benefit for patients with Excision repair cross-complementation group 1 (ERCC1) negative tumor expression. A proteomics biomarker model provided valuable information for prediction of survival and pharmacokinetics of 5-FU showed a correlation with treatment-related toxicity. Although it remains unclear if additional chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity, could potentially benefit from this treatment option based on our exploratory biomarker research.We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m2) on day 1 and S-1 (25 mg/m2 twice daily) on days 1–14. The primary endpoint was feasibility, defined as ≥50% completing treatment. We performed exploratory propensity-score matching to compare survival, ERCC1 and Thymidylate Synthase (TS) immunohistochemistry analyses, proteomics biomarker discovery and 5-FU pharmacokinetic analyses. Forty patients were enrolled and 48% completed all adjuvant cycles. Median dose intensity was 98% for S-1 and 62% for oxaliplatin. The main reason for early discontinuation was toxicity (67%). The median recurrence-free and overall survival were 28.3 months and 40.8 months, respectively (median follow-up 29.1 months). Survival was not significantly prolonged compared to a matched cohort (p = 0.09). Patients with ERCC1 negative tumor expression had significantly better survival compared to ERCC1 positivity (p = 0.01). Our protein signature model was predictive of survival [p = 0.04; Area under the curve (AUC) 0.80]. Moreover, 5-FU pharmacokinetics significantly correlated with treatment-related toxicity. To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research.

A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib As Frontline Therapy for Patients with MYC-Aberrant Lymphoid Malignancies: The Daciphor Regimen

A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib As Frontline Therapy for Patients with MYC-Aberrant Lymphoid Malignancies: The Daciphor Regimen

Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a Lysa Multicenter, Phase II Study. “the TOTAL Trial”

Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a Lysa Multicenter, Phase II Study. “the TOTAL Trial”

Abstract ES8-3: Everything Comes at a Price - Toxicity, Cost and Adherence to Endocrine Therapy

Abstract Despite the proven efficacy of aromatase inhibitors (AIs) for the treatment of hormone-sensitive breast cancer (BC) adherence to therapy for the full duration of 5-years is suboptimal. Adherence is likely even lower for extended adjuvant therapy for up to 10-years. Issues related to non-adherence are increasingly important, as analyses from prospective randomized trials show compliance to endocrine therapy is associated with improved disease-free survival. The reasons for non-adherence to hormonal therapy are multifactorial. Barriers to compliance include patient, physician, medication and system related variables and poor compliance is usually associated with a combination of these factors. Characteristics associated with non-adherence include very high and low age, minority race, being single, increased number of comorbidities, lack of knowledge about efficacy of AI therapy, history of non-adherence to other chronic medications, limited insurance status, and higher out of pocket costs. Side effects from hormonal therapy is the most common reason for early discontinuation. AI arthralgia has been estimated to affect 45-60% of patients, many of whom report severe or continuous pain. One study reported an overall AI discontinuation rate of 32.4% within 2 years due to adverse effects, 24.3% specifically due to musculoskeletal symptoms, which was the primary reason for discontinuation. There is no consensus on the best treatment for AI arthralgia. The most commonly used therapy is NSAIDs, although there are no formal data testing their efficacy for AI arthralgia, and they are associated with potentially severe adverse effects. Randomized controlled trials have shown benefits from exercise (aerobic and strength training exercises), acupuncture, omega-3-fatty acids and duloxetine compared to placebo for AI arthralgia. Studies have also demonstrated improvement in symptoms over time even among patients receiving placebo. Various educational interventions have also been studied to improve adherence. A systematic review of behavioral interventions to enhance adherence to hormone therapy found five articles that met inclusion criteria and none reported the interventions significantly enhanced adherence compared to usual care. All evaluated educational interventions with or without reminders or navigation. In addition, a multicenter randomized clinical trial of patients with early stage breast cancer on AI’s found that bi-weekly unidirectional text messages for 36 months focused on overcoming potential barriers to medication adherence did not result in improved adherence to hormonal therapy. It is likely that improving long-term adherence will likely require sustained behavioral interventions and support. Citation Format: DL Hershman. Everything Comes at a Price - Toxicity, Cost and Adherence to Endocrine Therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES8-3.

Aerobic capacity attainment and reasons for cardiopulmonary exercise test termination in people with cancer: a descriptive, retrospective analysis from a single laboratory.

Aerobic exercise prescriptions in clinical populations commonly involve target intensities based on cardiopulmonary exercise tests (CPET). CPETs are often discontinued prior to a patient achieving true maximum oxygen consumption (VO2 max) which can adversely affect exercise dose and efficacy monitoring; however, reasons for early discontinuation are poorly reported. Accordingly, we explored the CPET termination reasons in persons with cancer participating in exercise intervention studies. This study comprised of an exploratory, descriptive analysis of retrospective CPET data (VO2 and anaerobic threshold) and termination reasons in a convenience sample of people with cancer participating in exercise intervention studies in a single laboratory. CPETs were standardized using the modified Bruce treadmill protocol with expired gas collection and analysis using a metabolic cart. VO2 max was considered "met" when participants demonstrated (a) oxygen consumption plateau or (b) two of the following criteria: rating of perceived exertion ≥ 9/10, respiratory exchange ratio ≥ 1.15, and/or heart rate of 95% of age-predicted maximum. The frequency and distribution of reasons for test termination relative to the number of CPET exposures for the participants were reported. Forty-four participants engaged in exercise studies between February 2016 and March 2018 provided data for the analysis. Participants completed up to three CPETs during this period (total of 78 CPETs in the current analysis). Eighty-six percent of all CPETs were terminated prior to achieving VO2 max verification criteria and no tests resulted in an oxygen consumption plateau. For those that did not demonstrate achievement of VO2 max verification criteria, reasons for discontinuation were distributed as follows: equipment discomfort-49%, volitional peak-36%, and physical discomfort-14.9%. For those who met VO2 max criteria, volitional peak was the most common reason for test termination (45.5%), followed by physical discomfort (36.4%), and equipment discomfort (18.2%). In our sample of cancer survivors, VO2 max criteria were infrequently met with equipment discomfort being a primary reason for participant-driven test termination. Protocol and equipment considerations are necessary for interpretation and application of CPET findings in clinical practice.

Skin Reaction Associated With Vortioxetine: Purpuric Rash

Cognitive impairments continue during the symptomatic period and remission in patents with major depressive disorder. Sexual dysfunctions may be seen in depression and also represent a frequent side effect of antidepressant treatment and one of the major reasons for early discontinuation of medications. Case Report: In this case report we present a 38-year-old female patient who experienced a side effect while receiving treatment for major depression. The patient was switched to vortioxetine 10 mg/day after 3 months of treatment with fluoxetine 40 mg/day due to continuing cognitive dysfunction and antidepressant-associated decreased libido. The patient developed an extensive purpuric rash on the anterior thighs on the third day of the treatment. The treatment was discontinued. The same side effect occurred after the re-initiation of vortioxetine treatment at a dose 5 mg/day. Reporting of observed side effects may be useful for clinicians since the number of case reports on vortioxetine is limited.

Treatment persistence with a fixed-dose combination of tadalafil (5 mg) and tamsulosin (0.4 mg) and reasons for early discontinuation in patients with benign prostatic hyperplasia and erectile dysfunction.

PurposeThe primary aim of this study was to assess treatment persistence with a fixed-dose combination (FDC) of tadalafil (5 mg) and tamsulosin (0.4 mg). This study also evaluated the reasons for early treatment discontinuation.Materials and MethodsThis retrospective observational study included patients with benign prostatic hyperplasia and erectile dysfunction who started an FDC treatment of tadalafil (5 mg) and tamsulosin (0.4 mg) between July 2017 and February 2018. Treatment persistence and reasons for early discontinuation were evaluated during the first 6 months. The cumulative discontinuation rate and differences in various parameters were assessed using Kaplan–Meier analysis and the log-rank test, respectively. Factors related to persistence were analyzed using a Cox proportional hazard model.ResultsOverall, 97 patients were included in the study. The cumulative persistence rate at 30, 90, and 180 days was 88.7%, 66.0%, and 54.6%, respectively. The cumulative persistence over 6 months differed significantly according to the administration of FDC therapy (log-rank p=0.005) and age (log-rank p=0.024). Younger patients (odds ratio, 2.049; p=0.021) and treatment-naive patients (odds ratio, 2.461; p=0.006) were more likely to discontinue therapy within 6 months. The common reasons for discontinuing therapy were side effects (63.6%) and perceived poor efficacy (22.7%).ConclusionsSide effects were reported to be the main reason for treatment discontinuation. Thus, to improve compliance for a once-daily FDC of tadalafil (5 mg) and tamsulosin (0.4 mg), it is recommended to select patients who show adaptation to a combination of α-blockers and phosphodiesterase type 5 inhibitors prior to FDC treatment.

Preliminary Outcomes of Letermovir Use for Cytomegalovirus Prophylaxis: A Retrospective Assessment at a Single Center

Introduction Cytomegalovirus (CMV) is associated with significant morbidity and mortality in the hematopoietic cell transplant (HCT) population. In the absence of prophylaxis, reactivation occurs in upwards of 80% of seropositive allogeneic HCT recipients and primary infections in roughly 15% of CMV-mismatched HCTs. Agents used to prevent clinically significant CMV (csCMV) including ganciclovir and foscarnet can be associated with toxicities including renal dysfunction and myelosuppression. Letermovir is a novel antiviral targeting the viral terminase complex and has demonstrated efficacy in preventing csCMV in adult CMV seropositive allogeneic HCT recipients with minimal associated toxicities. Objectives To describe a single center experience of the use of letermovir as primary and secondary prophylaxis in adult allogeneic HCT recipients. Methods This retrospective analysis assessed 25 adult HCT patients receiving letermovir for primary or secondary prophylaxis between January 1, 2018 and September 24, 2018. Primary prophylaxis per hospital protocol was given through approximately d+100 in CMV seropositive recipients and also allowed in CMV seronegative recipients with seropositive donors. csCMV was defined as CMV viremia necessitating preemptive therapy or CMV disease. Patients were evaluated for development of csCMV on letermovir prophylaxis, early cessation of prophylaxis due to perceived toxicities, and development of csCMV post-cessation of primary prophylaxis. Results Twenty-two patients received letermovir for primary CMV prophylaxis. The primary underlying disease was AML (7/22, 32%). CMV serostatus was as follows: D-/R+ (9/22, 41%), D+/R+ (9/22, 41%), D+/R- (4/22, 18%). Letermovir was initiated ata median of 5.5 days post-transplant. Median letermovir duration was 95 days post-transplant. Early cessation due to perceived toxicities occurred in 41% (7/22) of patients. Reasons for early discontinuation were ongoing cytopenias (4/7, 44%) and nausea (3/7, 33%). No csCMV developed during therapy. In patients completing the intended primary prophylaxis (n = 10), thus far no patients have developed csCMV within a median duration of 150 days post letermovir cessation. Three patients received letermovir for secondary prophylaxis. All were CMV seropositive and high risk on basis of haploidentical donors (2/3, 67%) and use of cord blood (1/3, 33%). Therapy was initiated a median of 57 days post-transplant with no patients developing csCMV on therapy. Conclusions Letermovir was an effective antiviral in both primary and secondary CMV prophylaxis and was generally well tolerated. Side effects directly related to letermovir were difficult to assess in this complex patient population. Close monitoring is required following cessation of primary prophylaxis. Prospective studies defining the optimal duration for letermovir prophylaxis are needed.

Ruxolitinib for the Treatment of Inadequately Controlled Polycythemia Vera without Splenomegaly: 156-Week Follow-up from the Phase 3 Response-2 Study

BACKGROUNDRuxolitinib (RUX), a potent Janus kinase (JAK)1/JAK2 inhibitor, is approved for hydroxyurea (HU)-resistant/-intolerant patients (pts) with polycythemia vera (PV) based on findings from the RESPONSE study (NCT01243944). RUX proved superior to best available therapy (BAT) in maintaining hematocrit (Hct) control without phlebotomy eligibility, normalizing blood cell count, reducing spleen volume, and improving symptoms in pts with PV with splenomegaly who are resistant to or intolerant of HU. RESPONSE-2 (NCT02038036) is a global, multicenter, open-label, phase 3 trial comparing RUX with BAT in HU-resistant or -intolerant pts with PV without splenomegaly. In the primary analysis at wk 28, RUX proved superior to BAT in controlling Hct without phlebotomy eligibility, normalizing blood cell count, and improving symptoms. Responses were durable at 80 wk of follow-up. Here we evaluate the long-term safety and efficacy of RUX after a follow-up of 156 wk.METHODSPatients were randomized 1:1 to RUX 10 mg twice daily or BAT; BAT patients could cross over to RUX starting at wk 28. The primary endpoint was Hct control at wk 28 (absence of phlebotomy eligibility [Hct >45% and ≥3% higher than baseline, or >48%] from wk 8 to 28, with ≤1 phlebotomy eligibility up to wk 8). The key secondary endpoint was complete hematologic remission (CHR; Hct control, white blood cell count <10×109/L, platelet count ≤400×109/L) at wk 28. Other endpoints included changes in patient-reported outcomes and in JAK2 V617F allele burden over time. Durability of Hct control (ie, primary response), CHR, and safety were evaluated at wk 156.RESULTSAt data cutoff (April 6, 2018), 65/74 RUX pts were still on treatment. Primary reasons for discontinuation were adverse events (AEs; 5.4%), consent withdrawal (2.7%), death, disease progression, and physician decision (1.4% each). All 75 BAT pts had discontinued; 58 pts had crossed over to RUX; 46 were ongoing. Reasons for early discontinuation in crossover pts were AEs (13.8%), consent withdrawal (3.4%), death (1.7%), and disease progression (1.7%). Median exposure was 168.5 wk for RUX, 28.4 wk for BAT, and, in crossover pts, 137.0 wk for RUX.At wk 156, durable Hct control was achieved in 41.9% of RUX pts (31/74). The Kaplan-Meier estimated median duration of Hct control had not been reached (Figure A). Durable CHR was achieved in 24.3% of RUX pts (18/74; estimated median duration, 35.9 weeks; Figure B). RUX also led to durable improvements in PV-associated symptoms, with approximately half of RUX pts (48%) continuing to achieve a ≥50% reduction in MPN-SAF TSS at wk 156. Pts in the RUX arm also continued to experience improvements in all 5 dimensions of the EQ-5D-5L assessment. Pts who crossed over to RUX derived benefits from RUX therapy as well, achieving Hct control following crossover, with Hct decreasing over time. As seen in RUX pts, crossover pts experienced a reduction in JAK2 V617F allele burden over time from the time of crossover.The safety profile of RUX was consistent with previous reports. The most common AEs were anemia (exposure-adjusted rate per 100 pt-years, 10.7), increased weight (8.5), arthralgia (6.8), and hypertension (6.0) in the RUX arm and anemia (12.8), nasopharyngitis (7.1), and increased weight (6.4) in pts after crossover. Of interest, exposure-adjusted rates of herpes zoster were 3.8 with RUX and 5.0 in crossover pts. Overall, exposure-adjusted rates of AEs with RUX were lower than those reported at 80 wk of follow-up. The exposure-adjusted rate of thromboembolic events was higher in the BAT arm (3.7; RUX, 2.6). As expected given prior HU exposure, nonmelanoma skin cancer was the most common second malignancy in RUX-treated pts (randomized, 3.4; crossover, 2.8). No RUX-treated pts developed AML; 1 pt (RUX arm; 0.4) developed myelofibrosis. Three pts died on study: 1 in the RUX arm (metastatic melanoma), 1 in the BAT arm (septic shock), and 1 after crossover (general health deterioration).CONCLUSIONSIn this 156-wk follow-up, RUX provided durable Hct control and CHR in pts with PV without splenomegaly. RUX was well tolerated, with 88% of randomized pts and 79% of crossover pts still receiving RUX at the time of this analysis. AEs were consistent with previous reports, and no new safety signals were observed. Overall, findings are consistent with those from RESPONSE and support RUX as the standard of care for second-line therapy in pts with inadequately controlled PV. [Display omitted] DisclosuresPassamonti:Novartis: Consultancy, Honoraria, Speakers Bureau. Palandri:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Saydam:Gilead: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria. Devos:Novartis: Consultancy; Takeda: Consultancy; Celgene: Consultancy. Vannucchi:Celgene: Membership on an entity's Board of Directors or advisory committees; ITALFARMACO: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Bensasson:Novartis: Employment. Kandra:Novartis: Employment, Research Funding. Morando:Novartis: Employment, Equity Ownership. Griesshammer:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Clinical Outcomes of the Oral Suspension vs Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections

Background Posaconazole is effective prophylaxis for invasive fungal infections (IFIs). We compared incidence of breakthrough IFI (bIFI) and early posaconazole discontinuation between patients receiving delayed-release tablet and oral suspension formulations.Methods This was a retrospective cohort study of patients receiving posaconazole at Oregon Health & Science University Hospital between 1/1/2010 and 6/30/2016. Oral suspension was the preferred formulation until 2/2014; afterwards the tablet was preferred. We included all courses of primary prophylaxis for each patient during the study period. Data were extracted from an electronic health record repository and via chart review. Three independent reviewers identified bIFI using European Organization for Research and Treatment of Cancer criteria. We assessed rationale for early discontinuation of posaconazole for patients that were still indicated for antifungal prophylaxis based on National Comprehensive Cancer Network (NCCN) criteria.Results547 patients received 859 courses of posaconazole (53% oral suspension and 48% tablet). Prophylaxis was indicated according to NCCN criteria in 91% of courses. The primary indications for prophylaxis were acute myelogenous leukemia (68%), graft-vs-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indication between patients receiving the different formulations. The overall incidence rate of bIFI was 4.15/10,000 posaconazole-days (16 total bIFI events). Incidence of bIFI was not significantly different between patients receiving the different formulations (P = 0.92). Posaconazole was discontinued early in 147 (17%) courses; frequency of discontinuation was not significantly different between the tablet (20%) and oral suspension (15%) formulations (P = 0.10). The primary reasons for early discontinuation were elevated liver function tests or QT prolongation (25%), inability to take an oral formulation (17%), and drug cost (17%).Conclusion Among patients receiving posaconazole prophylaxis, incidence of bIFI was low and not significantly different between those receiving the tablet vs oral suspension formulations.Disclosures J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. J. S. Lewis II, Merck & Co.: Consultant, Consulting fee. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant

Early clinical progression in patients with gynecologic malignancies receiving immunomodulatory antibody therapy.

e17087 Background: The success of immunomodulatory antibodies have led to their increasing investigation in GYN cancers. Many of these patients, however, discontinue the drugs early in treatment due to symptomatic progression, making it challenging to assess clinical benefit and late responses associated with these agents. Here, we describe the clinical characteristics underlying early progression requiring immunotherapy discontinuation in order to better guide patient selection for such trials. Methods: A retrospective analysis was performed on all GYN cancer patients treated with immunomodulatory antibodies at MSKCC between 1/2013 and 6/2016. Patients were defined as early progressors if they had clinical/radiographic disease progression before 12 weeks which required therapy discontinuation. Logistic regression was applied to model the relationship between baseline clinical and radiographic characteristics and early progression. P&lt;0.05 was considered to be statistically significant. Results: A total of 105 patients met the inclusion criteria, with 74 (71%) with ovarian cancer. Therapeutic targets included CTLA-4 (3%), and PD-1/PD-L1 alone and in combination with other targets (97%). Of these, 55 (52%) met the criteria for early progression requiring therapy discontinuation (median therapy duration 7 weeks, range 1.6-12.1). There was an increased risk for early progression in patients with pre-treatment ascites (p=0.005, OR 6.4, 95% CI 1.7-23.7), and with baseline bulky disease, defined by at least one tumor measuring ≥ 5cm, compared to patients with tumors &lt;5cm (p=0.001, OR 4.1, 95% CI 1.7-9.9). Clinical symptoms/deterioration were the reason for early discontinuation in 35 (64%) of the patients, with symptomatic ascites and abdominal pain as the most common complaints. Conclusions: Symptomatic clinical progression of peritoneal disease leading to early discontinuation of immunomodulatory antibody therapy is common in patients with GYN cancers and is associated with increased pre-treatment disease volume. The extent of peritoneal disease should be taken into strong consideration when selecting GYN cancer patients for trials with immunomodulatory antibody therapy.

Feasibility and Efficacy of Dose Adjusted Melphalan - Prednisone - Bortezomib (MPV) in Elderly Patients ≥ 75 Years of Age with Newly Diagnosed Multiple Myeloma; the Non-Randomised Phase II HOVON 123 Study

BACKGROUNDThere is a high rate of toxicity-related discontinuation in elderly patients with NDMM, which in general is higher in patients ≥75 years. Therefore, we investigated the feasibility of a dose-adapted MPV scheme in patients ≥75 years and whether the International Myeloma Working Group frailty score (fit, unfit, and frail) predicts feasibility. Moreover, geriatric assessments, including functional assessments, were performed in order to design a model for more precise prediction of feasibility of treatment.METHODSPatients were treated with 9 cycles of MPV: Mel 6 mg/m2, day 1-4; Pred 30 mg/m2, day 1-4; and Bort 1.3 mg/m2 day 1,8,15 and 22 of a 35-day cycle. This first planned analysis on discontinuation rate was restricted to the first 100 eligible consecutive patients out of 240 planned patients. A preliminary analysis of grip strength and walking speed was performed, comparing tertiles.RESULTSOf the 96/100 evaluable patients, none were fit (because of age ≥75 years), 23/96 (24%) were unfit and 64/96 (67%) were frail (9/96 (9%) unknown). 28/64 (44%) frail patients were aged 75-80, and 8/64 (13%) patients were defined frail based on age >80 years only. Frail patients were found to have significantly less grip strength and lower walking speed as compared to unfit patients (see table 1), both for men and women. However, 19% (male) and 15% (female) of the patients with low grip strength were not frail, but unfit. For slow walking speed these percentages were 13% and 7% respectively, indicating these tools might be complementary to the IMWG frailty score in predicting outcome.The median follow up was 16 months. The discontinuation rate of MPV in the total population was 49%; 30% in unfit and 55% (including 7% discontinuation of bortezomib only) in frail patients (p=0.055). In patients >80 years (by definition frail) discontinuation rate was higher (69% (including 11% bortezomib only)) than in patients aged 75-80 years (37%; p=0.003). Reasons for early discontinuation in unfit versus frail were: progressive disease 1/7 vs 4/31, toxicity 3/7 vs 10/31, death 0/7 vs 4/31, non-compliance 1/7 vs 8/31, other 2/7 vs 5/31. In 72% 6 cycles of MPV were found to be feasible, both in unfit (78%) and frail (73%) patients.Response on protocol was ≥PR 69%, ≥VGPR 29% and ≥CR 7%, not significantly different in unfit versus frail patients. Median progression free survival (PFS) was 17 months: 22 for unfit and 17 months for frail patients (p=0.38). Overall survival (OS) at 18 months was 76%: 88% for unfit and 71% for frail (p=0.26) patients.ConclusionsTreatment of elderly NDMM patients ≥75 years with 9 cycles of dose-adjusted MPV results in a high discontinuation rate of 49%: 30% in unfit versus 55% in frail patients, indicating the need for further treatment adjustment and more precise selection of patients. Concerning the first; 6 cycles were found to be feasible in the majority of both unfit and frail patients. Concerning the latter; a preliminary analysis of functional geriatric assessments showed significantly lower performance in frail compared to unfit patients. Moreover, the results of functional geriatric assessments were found to add to the IMWG frailty score, hopefully leading to a better prediction of the feasibility of treatment in elderly NDMM patients.Functional assessments in unfit versus frail patients 1 p=0.18 2 p=0.012 3 p=0.0374 p=0.014Additional cognitive and nutritional geriatric assessments and biomarkers (sarcopenia and senescence markers) were performed in all patients.FISH analysis of isolated plasma cells will be available in the majority of patients.This trial was registered at www.trialregister.nl (NTR 4244), EudraCT 2013-000320-33, and supported by the Dutch Cancer Society (project number VU 2013-6411 ) and by an unrestricted grant from Janssen-Cilag. [Display omitted] DisclosuresZweegman:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Ypma:Advisory Board Sanofi (Plerixafor): Membership on an entity's Board of Directors or advisory committees. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. van de Donk:BMS: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Amgen: Research Funding. Sonneveld:Karyopharm: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.