ALBERT

Description: Introduction: Renal impairment (RI) is common in multiple myeloma (MM), with up to 40% of the patients (pts) experiencing this complication during the course of their disease. RI increases risk of early death and affects disease management in multiple ways, as it may complicate treatment options and dosing, and render pts more susceptible to infections and prolonged hospitalizations. Therefore, there is an urgent need to restore renal function in these pts in order to improve their quality of life and prognosis. Bortezomib-based therapies are the most commonly used in pts with RI, but eventually pts may become refractory to bortezomib and other drug classes such as IMIDs. Thus, new therapeutic options are needed in order to manage pts with MM and RI who fail these drugs. Daratumumab, an IgG1κ human monoclonal antibody that targets CD38, has shown durable responses and a favorable safety profile in heavily pretreated pts with relapsed/refractory MM (RRMM) as monotherapy. Pharmacokinetic analyses suggest that there are no clinically important differences in exposure to daratumumab in pts with normal or impaired renal function, but the available data on safety and efficacy of pts with RRMM and severe RI is scarce. Methods: DARE is a prospective, open-label, multicenter, phase 2 study, which completed the enrolment of 38 adult pts with documented RRMM and severe RI, defined as either eGFR

Description: Introduction: Pomalidomide (POM) plus low-dose dexamethasone (POM/LoDex) is a standard of care for patients with relapsed/refractory multiple myeloma (RRMM), who have received ≥2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT). In view of the limited real-world evidence on POM/LoDex effectiveness, this study aimed to provide insight into progression-free survival (PFS), response to treatment and drug utilization patterns in the routine clinical practice in Greece. Methods: 'POWERFUL' (NCT03353545) was a non-interventional, multicenter, retrospective and prospective study of adult RRMM patients, initiated on POM/LoDex between 01-Jan-2016 and 28-Feb-2019 per the approved label. Patients who had received up to one POM/LoDex cycle were consecutively enrolled between 16-Nov-2017 and 21-Feb-2019 (prospective recruitment phase). One month prior to completion of this phase, aiming to facilitate recruitment of the target size, patients, whose treatment with POM/LoDex was ongoing but 〉1 cycles had been received or for whom treatment was discontinued, were consecutively enrolled in reverse chronological order, based on POM/LoDex start date (retrospective recruitment). Patients were observed until the earliest point of disease progression (PD), death, informed consent (IC) withdrawal, treatment discontinuation for reason other than PD or start of next antimyeloma therapy, physician's decision, or last patient enrolled plus up to 12 months of treatment. IC or consent waiver for deceased subjects was obtained. Safety data were collected prospectively. Results: Eligible patients (N=99; 75 with prospective and 24 with a purely retrospective follow-up) were recruited by 18 hematology departments. The median (IQR) observation period was 8.8 (4.2-15.4) months. Baseline patient characteristics are presented in Table 1. Fifty patients (50.5%) started POM/LoDex as third-line treatment. POM was initiated at 4 mg/day on days 1-21 every 28 days in 75.8% of the patients. A median of 8 (range: 1-38) cycles were received at a median POM dose of 4 mg/day (range: 1-4), over 8.3 (range: 0.3-47.6) months. The POM dose reduction and interruption rates were 28.3% and 59.6%, respectively. Of the patients, 37.4% were treated for ≥ one year. Treatment was discontinued in 81.8%, due to PD (56.8%), safety reasons (22.2%), death (6.2%), other reasons (9.9%), and due to loss of follow-up (4.9%). The investigator-assessed overall response rate (≥partial response [PR]) was 32.3%; best response rates were: stringent complete or complete response (7.1%), very good PR (8.1%), PR (17.2%), minimal response (11.1%), stable disease (21.2%), PD (12.1%), and non-evaluable response (23.2%). Median time to response and duration of response in patients achieving ≥PR was 3.2 [95% confidence interval (CI): 2.6-3.6] and 15.8 (95%CI: 11.3-not reached) months, respectively. Over a Kaplan-Meier estimated median follow-up of 13.8 months, the median PFS was 10.5 months (95%CI: 7.4-14.4) [13.0 vs. 8.8 months for patients treated in the third vs. the fourth- and beyond line (log-rank p=0.494), and 13.0 vs. 8.8 months for patients treated with POM/LoDex only vs. those co-administered other antimyeloma agents (log-rank p=0.411)]. The estimated 6-, 12-, 24- and 36-month PFS rates were 70.3%, 48.3%, 20.1% and 12.0%, respectively. Multivariate Cox regression analysis of the impact of baseline characteristics on PFS indicated male sex [hazard ratio (HR)=2.08; 95%CI: 1.12-3.89; p=0.021] and higher than normal serum lactate dehydrogenase levels (HR=2.84; 95%CI: 1.39-5.81; p=0.004) as negative predictors of PFS. Over a median safety data collection period of 7.6 months (range: 0.4-18.6), the POM-related adverse events (ADR) incidence rate in the safety-evaluable population (i.e., 75 patients with prospective follow-up) was 42.7% (73 events). Only neutropenia (13.3%) was reported at a frequency ≥10%. The serious ADR rate was 18.7%, whereas grade ≥ 3 hematological and non-hematological ADR rates were 8.0%, and 5.3%, respectively. Conclusion: In this Real-World dataset from Greek centers, POM/LoDex, administered in the third-line and beyond setting of RRMM, displayed a longer PFS than in controlled clinical trials, which was not impacted by the treatment line and concurrent receipt of other antimyeloma agents. About one-third of patients achieved at least PR with an about 16-month response duration. Disclosures Terpos: Amgen: Honoraria, Research Funding; Sanofi: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; BMS: Honoraria. Repousis:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hatjiharissi:Roche: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Assimakopoulou:Genesis pharma SA: Research Funding. Vassilopoulos:Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding. Pouli:Genesis pharma SA: Research Funding. Spanoudakis:Genesis pharma SA: Research Funding. Michali:Takeda: Research Funding; Genesis pharma SA: Research Funding. Pangalis:Genesis pharma SA: Research Funding. Poziopoulos:Genesis pharma SA: Research Funding. Kyrtsonis:Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pappa:Genesis pharma SA: Research Funding. Symeonidis:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; WinMedica: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Astellas: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi/Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Georgopoulos:Genesis pharma SA: Research Funding. Zikos:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Papadaki:Genesis pharma SA: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dadakaridou:Genesis pharma SA: Research Funding. Karvounis-Marolachakis:Genesis pharma SA: Current Employment. Patos:Genesis pharma SA: Current Employment. Katodritou:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theagenion Cancer Hospital: Current Employment; Takeda: Honoraria, Other: Expenses, Research Funding; Genesis Pharma: Honoraria, Other: Expenses, Research Funding; Abbvie: Research Funding; Karyopharm: Research Funding.

Description: Background Lenalidomide resistance is one of the main emerging therapeutical concerns in MM. SsCD138 levels were shown of prognostic significance in MM at diagnosis while their contribution during disease course has not been evaluated. Aims To evaluate ssCD138 possible prognostic contribution in MM patients treated with Lenalidomide. Patients and methods : Sixty-nine patients treated with Lenalidomide were included in the study. All received dexamethasone (RD) but one maintenance. Medical records were reviewed and frozen sera samples were tested after patient's informed consent. SsCD138 levels were determined by ELISA (Diaclone Research) according to the manufacturer's instructions. Median age of patients was 67 years with 50% women. Immunoglobulin type was IgG in 67% patients, IgA in 22%, Light-Chain in 10% and IgD in 1%. ISS 1, 2 and 3 were 37%, 24% and 39% respectively. ssCD138 were measured at RD initiation, best response and relapse. Median value was used as cut off and any concentrations above median were defined as "High". Median PostLenOS was 27mo, median time to next treatment (TNT) was 12,5mo. Time from RD initiation to the second relapse after RD (LenPFS2) was 24,5mo. Median number of previous treatment lines was 3. Forty healthy individuals were also tested. Statistical analysis was performed using SPSS software v.25. Results: Median ssCD138 was 234 ng/ml (15-841) at RD initiation, 97 ng/ml(12-1500) at plateau and 247(51-395) at relapse while it was 52 ng/ml (21-1070) in Healthy Individuals. Patients achieving VgPR and better had more than 50% reduction in ssynd-1 levels from treatment initiation to plateau (r=0,344, p=0,05). Patients with High ssynd-1 levels at RD initiation presented shorter LenPFS 2 (p=0,011) and TNT (p=0,018). Factors measured at RD initiation impacting on LenPFS2 were ssCD138 levels (HR:2 .p=0,025), abnormal LDH (HR:4,47 ,p=0,0001), ISS (HR=1,54, p=0,008) and b2-microglobulin〉5.5mg/L(HR: 2,23, p=0,009), Bone Marrow Infiltration (BMINF)〉60% (HR : 2,39, p=0,048), albumin5.55mg/L (HR:1,76, p=0,008) and Free Light Chain Ratio(FLCR)〉100 (HR:2,08, p=0,000), albumin60% (HR : 2,18, p=0,01), Hb5.5mg/L (HR:1.61 ,p= 0,031), FLCR〉100 (HR:2,8 , p=0,0001) levels, albumin60% (HR : 2,8, p=0,002). Based on the independent variables patients were assigned a score of 1 with both FLCR〉100 and elevated ssCD138 levels and 0 with both these values normal. Patients with 1 point presented an estimated TNT of 4 Vs 14 months (p=0,001) and shorter LenPFS of 11 Vs 28 months (p=0,001). The estimated PostLenOS was 15 Vs 33 months in patients with 1 and 0 point respectively (p=0,005). Conclusion SsCD138 levels in MM patients treated with RD were significantly associated with LenPFS2 and TNT. A Prognostic score based on ssCD138 and FLCR〉100 was shown effective for the prediction of PostLenOS, LenPFS2 and TNT. These results suggest that soluble syndecan-1 levels can discriminate patients at risk to the lenalidomide resistant early. Indeed validation in larger cohort is necessary. Disclosures Panayiotidis: ASH: Honoraria; Phizer: Honoraria; Roche: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Takeda: Honoraria; Novartis: Honoraria, Research Funding; Genesis: Honoraria, Research Funding; Janssen: Honoraria; Gilead: Honoraria. Kyrtsonis:Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Osteolytic lesions (OL) is a devastating characteristic of multiple myeloma (MM) that decreases patients (pts) quality of life. The interaction between MM plasma cells and the bone microenvironment leads to intracellular and intercellular pathways that adversely alter the delicate balance between bone formation and bone resorption. Pre-clinical studies have shown that anti-CD38 therapy inhibit osteoclast formation. Daratumumab (dara), an IgG1κ human monoclonal antibody that targets CD38, has shown deep hematological responses in heavily pre-treated pts with relapsed/refractory MM (RRMM) as monotherapy. The aim of the REBUILD study is to evaluate the effect of dara monotherapy on bone metabolism in advanced RRMM pts. Methods: REBUILD is a prospective, open-label, multicenter, phase 2 study which has completed the enrolment of 57 pts with documented RRMM and ≥2 prior lines of therapy, including lenalidomide and a proteasome inhibitor. Pts had a Karnofsky Performance Status score of ≥70, and a creatinine clearance of ≥30 mL/min. Exclusion criteria included previous treatment with dara or other anti-CD38 therapy. Pts receive dara at a weekly dose of 16 mg/kg for Cycles 1-2, every 2 weeks for Cycles 3-6 and every 4 weeks thereafter. The primary endpoint of this study was the change from baseline in the bone resorption markers C-terminal telopeptide of collagen type I (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) after 4 months of dara monotherapy. Secondary endpoints include the change at 4 months from baseline in bone formation markers (bone-specific alkaline phosphatase [bALP], osteocalcin [OC], and procollagen type-I N-propeptide [PINP]); markers of osteoclast regulation (receptor activator of nuclear factor kappa-B ligand [RANKL], osteoprotegerin [OPG] and chemokine (C- C motif) ligand-3 [CCL-3]); markers of osteoblast control (sclerostin [SCL], dickkopf-1 [DKK-1]), and progression-free survival (PFS). This preliminary analysis included pts who received the first dose of study treatment at least 5 months before the cut-off date (01/05/2020). Results: Fifty-one pts were enrolled in 6 sites; among them 29 pts had bone markers and clinical data available on baseline and after 4 months of study treatment and are included in the present analysis. Median age was 73 years, and approximately half of them were female (15 pts, 52%). Median number of previous therapies was 3 (range: 2-5). Fifteen pts (52%) had 〉10 osteolytic lesions at study initiation, and only 4 pts (14%) received bisphosphonates together with dara monotherapy. The median changes in CTX and TRACP-5b levels for all pts (n=29) after 4 months in study treatment were 3.9% and -2.2%, respectively. Overall, 10 pts (35%) had ≥ 30% reduction in CTX and 5 pts (17%) in TRACP-5b levels. The median changes after 4 months of dara monotherapy for pts with a response [pts who achieved partial response or better (≥PR; n=18, 62%)] were 3% for CTX and -3% for TRACP-5b; among pts with no response [minimal response, stable disease, disease progression, or no response assessment prior to death (n=11; 38%)] 4% for CTX, and 9% for TRACP-5b. The median changes in bone formation markers for all pts after 4 months of dara were 24.5% for bALP, 116.8% for OC, and 15.7% for PINP. The differences for pts with a response versus pts without a response were respectively 26% versus 18% for bALP, 190% versus -61% (p=0.020) for OC, and 22% versus -3% for PINP. Other major differences in 4 months of dara monotherapy were the decrease in DKK-1 by 49% in pts with a response versus 2% increase in pts with no response, and the decrease in CCL3 by 15% in pts with response versus 101% increase in pts with no response (p=0.039). The median PFS for all 51 pts was 4.6 months (95% CI: 2.8-7.2). Conclusions: Monotherapy with dara has a positive effect on bone metabolism even in these highly pre-treated pts with MM. Reduction of TRACP-5b and of CCL-3 in responsive pts suggests an inhibitory effect on osteoclasts by dara. Interestingly, we found that there is a strong bone formation effect in all pts treated with dara monotherapy, especially in those who responded to therapy, i.e. OC had a 2-fold increase after 4 months of therapy. This is at least partially due to the reduction of DKK-1 (osteoblast inhibitor) in responding patients. Based on these positive results a preclinical study on the effect of dara on bone cells is currently being performed. Disclosures Terpos: Amgen: Honoraria, Research Funding; BMS: Honoraria; Sanofi: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding. Kastritis:Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Hatjiharissi:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Abbvie: Honoraria; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Katodritou:Theagenion Cancer Hospital: Current Employment; Karyopharm: Research Funding; Abbvie: Research Funding; Genesis Pharma: Honoraria, Other: Expenses, Research Funding; Takeda: Honoraria, Other: Expenses, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Verrou:Abbvie: Honoraria; Amgen: Honoraria; Genesis: Honoraria; Roche: Honoraria; Takeda: Honoraria; Karyopharm: Research Funding; Janssen Cilag: Honoraria, Research Funding. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Leonidakis:Health Data Specialists S.A.: Current Employment. Delimpasi:Janssen: Honoraria; GENESIS: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Kyrtsonis:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Papaioannou:Gilead: Honoraria; Genesis Pharma: Honoraria; Janssen-Cilag: Honoraria; Alexion: Membership on an entity's Board of Directors or advisory committees. Symeonidis:Sanofi/Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; WinMedica: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Astellas: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees.

Description: Introduction Venetoclax, a novel BCL2 inhibitor, used either as monotherapy or in combinations, induces rapid disease control , with durable clinical remissions, especially in patients with deep responses. In the Venetoclax era, minimal residual disease(MRD) is a new endpoint in CLL studies. MRD negativity is associated with better clinical outcomes (Jain N, et al. ASH 2019, abstract 186, Tam CS, et al. ASH 2019, abstract 642). Aim We present our single-center MRD data from a cohort of patients with relapsed/refractory(RR) CLL, treated with venetoclax monotherapy. Patients and Methods We collected data from 24 R/R CLL patients who have been treated with venetoclax monotherapy until progression, in the context of VENICE-1 study (NCT02756611) in our department between 11/2016 and 1/2018. MRD was locally evaluated with 10-colour flow cytometry(FC) according to ERIC guidelines, with the cut off of 1%) cut off as high-positive. Peripheral blood(PB) MRD was assessed every 3-6 months. At week48 (1 year), CT scans were performed for response assessment. Bone marrow (BM) biopsy and BM MRD at week48 were also performed in pts with CT confirmed CR. Results Between 11/2016 and 1/2018, 24 patients started treatment with venetoclax monotherapy. Our patients' baseline characteristics are shown in table 1. Disease responses and patients' treatment status as of end-July 2020 are shown in table 2. Progression free survival(PFS) and overall survival at 34 months is estimated 91.6% and 87.5% respectively. Four patients (16.7%) had to reduce their daily Venetoclax dose due to hematological toxicity: 2 to 300mg due to neutropenia and 2 to 200 and 100mg due to thrombocytopenia. MRD results at week 48 are shown in table 3. Sixteen patients have paired PB and BM MRD results (15 at week 48 and 1 at week 24) with 87.5% concordance (14 patients). In seven MRD negative patients MRD conversion (2 consecutive samples) was observed, after a median time of 16 m(6-28): six patients to low-positive and one to high-positive. The high-positive MRD-converted patient presented clinical relapse at the 2nd high-MRD positive sample, according to iwCLL criteria. One of 6 low-positive MRD-converted patients, became MRD negative again at a later time-point. Conclusion Our single-center data from 24 CLL patients enrolled in the Venice-1 study reveal high concordance of PB and BM MRD at week48. Higher PB MRD negativity rate at week 48 is observed (79.2%) in comparison to Venice trial (Kater A, et al. EHA 2020, S156) due to differences in MRD methodology/number of evaluable patients. Our FC MRD data show that MRD conversion from negative to low-positive may be observed during continuous Venetoclax treatment, without clinical disease progression. This observation, along with high PFS at 34 months (91.5%) confirms the importance of continuing Venetoclax therapy in RR CLL patients when given as monotherapy. Disclosures Kyrtsonis: Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Panayiotidis:Genesis: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Janssen: Honoraria; Gilead: Honoraria; Takeda: Honoraria; Phizer: Honoraria; ASH: Honoraria.