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7503 Background: To date, an overall survival (OS) benefit from upfront treatment for new treatment combinations over existing approaches has rarely been shown in first-line classical Hodgkin lymphoma (cHL). With the introduction of newer active therapies for relapsed/refractory disease, demonstration of improved OS with first-line therapy has been challenging. In ECHELON-1 (NCT01712490), 5-year follow-up analyses supported the long-term progression-free survival (PFS) benefit with first-line brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients (pts) with stage III/IV cHL, independent of interim positron emission tomography status. A+AVD had a manageable long-term safety profile, with numerically fewer second malignancies and a greater number of pregnancies reported vs ABVD (Connors et al, NEJM 2018; Straus et al, Lancet Haematol 2021). We report a prespecified OS analysis after approximately 6 years’ follow-up (cut-off, June 1, 2021). Methods: Pts were randomized 1:1 to receive up to 6 cycles of A+AVD (n = 664) or ABVD (n = 670) on day 1 and 15 every 28 days. OS was the key secondary endpoint and was an event-driven, pre-specified, alpha-controlled analysis in the intention to treat population. Results: At a median follow-up of 73 months, 39 and 64 OS events occurred in A+AVD and ABVD arms, respectively: OS significantly favored A+AVD vs ABVD (HR 0.590; 95% confidence interval [CI] 0.396–0.879; p = 0.009). Estimated 6-year OS rates (95% CI) were 93.9% (91.6–95.5) vs 89.4% (86.6–91.7) with A+AVD vs ABVD, respectively. There was a consistent OS benefit for A+AVD vs ABVD across prespecified subgroups. The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR 0.678 [95% CI 0.532–0.863]). Overall, A+AVD had a comparable long-term safety profile to ABVD. Treatment-emergent peripheral neuropathy continued to resolve or improve in both arms, with 86% (379/443) and 87% (249/286) of cases in the A+AVD and ABVD arms either completely resolving (72% vs 79%) or improving (14% vs 8%) by last follow-up. Fewer second malignancies were reported in the A+AVD vs ABVD arm (23 vs 32). More female patients reported pregnancy (49 vs 28) or live births (42 vs 19 in females) in the A+AVD vs the ABVD arm; no stillbirths were reported. No new safety signals were identified. Conclusions: A+AVD treatment resulted in a statistically significant 41% reduction in the risk of death vs ABVD, with a manageable safety profile consistent with prior reports. These outcomes confirm A+AVD as a preferred option for pts with previously untreated stage III/IV cHL. Clinical trial information: NCT01712490.

Abstract Background To describe response to therapy of small bowel (SB) Crohn’s disease (CD) at CT or MR enterography (CTE/MRE) in patients on vedolizumab. Methods Patients with SB CD who underwent CTE/MRE exams greater than 12 months apart on vedolizumab therapy were included. Length (in cm) and inflammation severity (EMBARK score) of inflamed SB segments were assessed. Changes in inflammation length of 3.4 cm or greater or inflammation severity of 2 EMBARK points or greater was categorized as response or progression, as appropriate, with development of newly inflamed segments, strictures, or penetrating complications also indicating progression. Patients not meeting the criteria for response or progression were categorized as having stable disease. Results Of 36 SB CD patients, the large majority had prior surgery (86%; 31), anti-TNF use (92%; 33), and internal penetrating (78%; 28) disease. Thirty-two patients had paired baseline and follow-up CTE/MRE exams without interval surgery, with clinical response observed in 24/32 (75%). Based on imaging response criteria, 22% (7/32; 95% CI: 9%–40%) had response, 50% (16/32; 95% CI: 32%–68%) were stable, and 28% (9/32; 95% CI: 14%–47%) had disease progression. Fifty-six percent of (18/32; 95% CI: 38%–74%) patients had clinical improvement with response or stable disease by imaging. Patients with stable disease had shorter median baseline lengths of SB inflammation (P = .012). Proportion of patients with colonic inflammation, perianal disease, or penetrating complications did not change. Conclusions Most patients on vedolizumab for over 12 months demonstrated response or stable SB disease when using objective cross-sectional radiologic imaging criteria using CTE/MRE.

Abstract Background Use of inflammatory biomarkers is common practice in ulcerative colitis (UC) management1. This study examined the utility of faecal calprotectin (FCP), C-reactive protein (CRP), and albumin biomarkers and their combination, for predicting outcomes of clinical remission and disease control (composite of clinical, endoscopic and histologic disease activity measures2) in patients (pts) with UC under therapy with vedolizumab (VDZ) or adalimumab (ADA) in the VARSITY study. Methods VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-control trial evaluating VDZ (anti-α 4β 7 integrin) vs ADA (anti-tumour necrosis factor-α) treatment in pts aged 18–85 years with moderate-to-severe UC (NCT02497469; EudraCT:2015-000939-33). Pts received either VDZ IV infusions (300 mg) on Day 1 and at Weeks (WKs) 2, 6, 14, 22, 30, 38, and 46 or ADA SC injections (40 mg), total dose 160 mg at WK1, 80 mg at WK2, and 40 mg every 2 weeks thereafter until WK50. In this post hoc analysis of data from 769 pts, the probability of clinical remission (total Mayo score ≤2, no subscore >1) and disease control (pt-reported outcome-2 [PRO2, Mayo subscores of stool frequency and rectal bleeding]; Mayo endoscopic subscore ≤1 [endoscopic improvement], and Robarts Histopathology Index score <5, [absence of histologic active disease]) were assessed at WK52 based on baseline and WK14 levels of dichotomized FCP (high-risk: ≥100 µg/g), CRP (high-risk: ≥5mg/L), and albumin (high-risk: <45 g/L) including the composite of high-risk CRP and FCP termed ‘inflammatory burden’ (IB). Results In comparison with biomarkers measured at baseline, FCP at WK14 was the most predictive of WK52 clinical remission after VDZ or ADA treatment3; WK14 FCP was also predictive of disease control using a combined endpoint of PRO2, endoscopy and histologic remission/response. VDZ-treated pts with low-risk FCP (<100 µg/g) at WK14 had a 76% chance of achieving WK52 clinical remission vs 35% for pts with high-risk FCP (70% vs 33% for ADA-treated pts with low and high-risk FCP, respectively). VDZ-treated pts with IB (high-risk levels of FCP and CRP) at WK14 had a 16% chance of clinical remission at WK52 vs a 57% probability for this endpoint in pts without IB at WK14; the risk difference for this composite biomarker was 42% (Table). Conclusion The addition of CRP to FCP as a composite biomarker of IB at WK14 after treatment initiation can be a useful negative predictor of pts who are likely to achieve significant long-term benefits, including remission and disease control, with VDZ or ADA treatment. References 1. Turner D, et al. Gastroenterology 2021;160(5):1570-38. 2. Danese S, et al. J Crohn’s Colitis 2021;15(Suppl1):S305–S305. 3. Dulai PS, et al. Gastroenterology 2021;160(6):S-46–7.

Abstract Background Darvadstrocel (DVS) is a suspension of expanded allogeneic adipose-derived mesenchymal (stromal) stem cells approved for the treatment of complex Crohn’s perianal fistulas (complex CPF). The INSPIRE (EUPAS24267) registry is a European observational, post-approval study designed to evaluate the real-world effectiveness and safety of DVS in patients with complex CPF for up to 36 months after DVS administration. Here we report clinical and safety outcomes from the first interim analysis at 6 months post treatment. Methods Patients with complex CPF treated with DVS according to local standard practice were eligible to enrol. Primary outcomes were clinical response (defined as closure despite gentle finger compression of ≥50% of external openings treated with DVS that were draining at baseline) and clinical remission (defined as closure despite gentle finger compression of all external openings treated with DVS that were draining at baseline). Outcomes were evaluated in the All Treated (AT) and Treated Per Protocol (PP) cohorts (Table 1) 6 months post treatment in patients who had received a single administration of DVS. The number and nature of adverse events (AEs), serious AEs (SAEs) are reported for the AT cohort. Results As of September 2021, 230 patients had enrolled, 225 met the inclusion criteria and 205 had complete treatment data and comprised the AT cohort, of these, 176 were treated per protocol. A total of 138 (AT) and 120 (PP) patients were 6 months post treatment, 66% (92/138) and 58% (69/120) had a 6-month visit, of which, 85% (78/92) and 100% (69/69) had evaluable data at Month 6, respectively. Baseline demographics and clinical and fistula characteristics are shown in Tables 1 and 2. In the AT and PP cohorts, respectively, 73% (57/78) and 74% (51/69) of patients had a clinical response, and 65% (51/78) and 65% (45/69) had clinical remission. Changes in Crohn’s disease (CD) activity (assessed with the Harvey–Bradshaw Index) post treatment were minimal, and most patients had no change in CD activity from baseline. In the AT cohort, 20% (41/205) of patients had ≥1 AE and 9.3% (19/205) had ≥1 SAE. There were no reports of ectopic tissue formation and no deaths. Conclusion This is the first real-world, multi-centre study reporting the effectiveness and safety data after DVS treatment for complex CPF. These interim analysis data are consistent with the pivotal ADMIRE-CD study in terms of effectiveness and safety. The ongoing status of the registry and small number of evaluable patients mean these data should be interpreted with caution, pending future analyses in larger numbers of patients with longer follow-up times.

Abstract Introduction: A number of cytogenetic abnormalities (CAs) are associated with poorer prognosis in MM, including del(17p), t(4;14), t(14;16), and amp1q21. There is a general consensus that treatment with proteasome inhibitors (PIs) benefits pts carrying these CAs (Sonneveld Blood 2016). This meta-analysis of four phase 3 studies assesses PFS benefit in pts receiving the oral PI ixa vs pbo regarding the specific adverse CAs. Methods: Pts in TOURMALINE-MM1 (N=722; relapsed/refractory MM; Moreau N Engl J Med 2016) and MM2 (N=705; newly diagnosed MM; Facon Blood 2021) received ixa plus lenalidomide-dexamethasone (Rd) vs pbo-Rd (1:1). Pts in TOURMALINE-MM3 (N=656; Dimopoulos Lancet 2019) and TOURMALINE-MM4 (N=706; Dimopoulos J Clin Oncol 2020) received ixa vs pbo (3:2) as maintenance following autologous stem cell transplant or as post-induction maintenance in transplant-ineligible pts, respectively. In TOURMALINE-MM1/MM2, CAs were centrally assessed on CD138 positive sorted cells from bone marrow samples collected at study entry using fluorescence in situ hybridization (FISH). Cutoff values for defining the presence of del(17p), t(4;14), and t(14;16) were 5%, 3%, and 3% positive cells, respectively, based on the false-positive rates (technical cutoffs) of the FISH probes used, and cutoff values of 3% (MM1) and 20% (MM2) were used for amp1q21. In TOURMALINE-MM3/MM4, cytogenetic assessment was performed locally using FISH or conventional karyotyping with locally defined thresholds for positivity. Results: 270/1227 (22%) vs 227/1019 (22%) evaluable pts receiving ixa-based vs pbo-based therapy had high-risk CAs [del(17p), t(4;14), t(14;16)]: 75 vs 62 in MM1, 60 vs 63 in MM2, 61 vs 54 in MM3, and 74 vs 48 in MM4. 957/1227 (78%) vs 792/1019 (78%) had complementary standard-risk CAs: 200 vs 216 in MM1, 231 vs 234 in MM2, 252 vs 152 in MM3, and 275 vs 190 in MM4. 555/1142 (49%) vs 479/955 (50%) evaluable pts receiving ixa-based vs pbo-based therapy had expanded high-risk CAs (high-risk CAs ± amp1q21): 155 vs 154 in MM1, 134 vs 146 in MM2, 116 vs 88 in MM3, and 150 vs 91 in MM4. 587/1142 (51%) vs 476/955 (50%) had complementary standard-risk CAs: 122 vs 126 in MM1, 164 vs 153 in MM2, 154 vs 89 in MM3, and 148 vs 108 in MM4. After a median follow-up in the pooled analysis of 25.6 months (mos; 12.7, 54.6, 29.7, and 21.3 mos in MM1, MM2, MM3, and MM4, respectively), the hazard ratio (HR) for PFS with ixa-based vs pbo-based therapy in pts with high-risk CAs was 0.74 (95% confidence interval [CI] 0.59-0.93; median 17.8 vs 13.2 mos) and 0.70, (95% CI 0.62-0.80; median 26.3 vs 17.6 mos) in pts with standard-risk CAs. In the subgroup analyses of expanded high-risk CAs, the HR for PFS with ixa-based vs pbo-based therapy in pts in the expanded high-risk group was 0.75 (95% CI 0.64-0.87; median 18.1 vs 14.1 mos; Figure 1) and 0.71 (95% CI 0.59-0.85; median 36.1 vs 21.4 mos) in the complementary standard-risk group. Analyses of PFS according to the presence of individual CAs (Figure 2) indicated differing magnitudes of PFS benefit. Notably, in pts with t(4;14) (n=124 vs n=102), the HR for PFS with ixa-based vs pbo-based therapy was 0.68 (95% CI 0.48-0.96; median 22.4 vs 13.2 mos), while for pts with amp1q21 (n=380 vs n=312), the HR was 0.77 (95% CI 0.63-0.93; median 18.8 vs 14.5 mos) and for pts with del(17p) (n=141 vs n=107) the HR was 0.80 (95% CI 0.59-1.09; median 15.7 vs 13.2 mos). Conclusions: This pooled analysis demonstrated a PFS benefit with ixa-based therapy vs pbo-based therapy regardless of the presence of specific adverse CAs, with a similar magnitude of benefit in pts with (expanded) high-risk CAs and the respective complementary standard-risk groups. However, due to the differences in study eligibility criteria and pt populations, ixa combined with Rd or as single-agent maintenance therapy may not abrogate the negative impact of high-risk CAs. Analyses of PFS in subgroups with specific CAs indicated that the greatest magnitudes of benefit (lowest HRs) with ixa-based vs pbo-based therapy were in pts with t(4;14) (HR 0.68) and pts with amp1q21 (HR 0.77), suggesting that the improved outcome with ixa-based vs pbo-based therapy in the expanded high-risk subgroup was primarily driven by PFS differences in pts with these more common CAs. Further study is needed, and additional sensitivity analyses will be presented in subsequent publications. Figure 1 Figure 1. Disclosures Chng: BMS/Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; Johnson and Johnson: Honoraria, Research Funding. Lonial: BMS/Celgene: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria. Morgan: Takeda: Honoraria. Iida: Amgen: Research Funding; Daiichi Sankyo: Research Funding; Glaxo SmithKlein: Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Chugai: Research Funding; Abbvie: Research Funding; Janssen: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding. Moreau: Sanofi: Honoraria; Celgene BMS: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Oncopeptides: Honoraria. Kumar: Bluebird Bio: Consultancy; Carsgen: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Novartis: Research Funding; Oncopeptides: Consultancy; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Beigene: Consultancy; Merck: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Twumasi-Ankrah: Takeda: Current Employment. Kumar: Takeda: Current Employment, Current holder of stock options in a privately-held company. Dash: Takeda: Current Employment, Current equity holder in publicly-traded company. Vorog: Takeda: Current Employment. Zhang: Takeda: Current Employment. Suryanarayan: Takeda: Current Employment. Labotka: Takeda: Current Employment. Dimopoulos: Janssen: Honoraria; Takeda: Honoraria; Beigene: Honoraria; BMS: Honoraria; Amgen: Honoraria. OffLabel Disclosure: Use of the oral proteasome inhibitor ixazomib for the initial treatment of multiple myeloma and as maintenance treatment following stem cell transplantation or induction therapy in newly diagnosed patients

Abstract Background: Two global, randomized, placebo (pbo)-controlled phase 3 studies of single-agent ixazomib (ixa) maintenance therapy are currently ongoing for newly diagnosed MM patients following primary therapy that included autologous stem cell transplantation (ASCT) (MM3, NCT02181413) or excluded ASCT (MM4, NCT02312258). Both trials have demonstrated statistically significant and clinically meaningful improvement in their primary endpoint of progression-free survival (PFS): for MM3, median 26.5 months (mos) ixa vs 21.3 mos pbo (hazard ratio [HR] 0.720, 95% confidence interval [CI] 0.582-0.890, P=0.002); for MM4, median 17.4 mos for ixa vs 9.4 mos for pbo (HR 0.659, 95% CI 0.542-0.801, P<0.001). Data for the key secondary endpoint, OS, have not previously been published. Methods: Full methods have previously been reported (Dimopoulos, Lancet 2019; Dimopoulos, J Clin Oncol 2020). Eligible patients (MM3, N=656; MM4, N=706) were randomized 3:2 to receive maintenance therapy with single agent ixa or pbo for a maximum of approximately 24 mos (26 cycles, to the nearest complete cycle) or until progressive disease or unacceptable toxicity, whichever occurred first. Results: At the most recent data cut-off (MM3, 29 January 2021; MM4, 15 October 2020), with median follow up of 64 mos and 36 mos, respectively, 27% (MM3, 174/656) and 29% (MM4, 203/706) of the intention-to-treat (ITT) population had OS events. In MM3, the 5-year Kaplan-Meier estimate for OS was 74% for ixa and 73% for pbo, though the median OS had not yet been reached in either arm (HR 1.008, 95% CI 0.744-1.367, P=0.958; Figure). In MM4, the 5-year Kaplan-Meier OS estimate was 55% for ixa and 56% for pbo, though the median OS had also not yet been reached in either arm (HR 1.136, 95% CI 0.853-1.514, P=0.382; Figure). No new safety signals were identified, and the incidence of new primary malignancies in both studies was similar between ixa and pbo. Conclusions: These most current OS data for MM3 and MM4 have not demonstrated a statistically significant difference for the ixa or the pbo arm to date. After 64 mos of follow-up in MM3, the risk of OS does not differ between the study arms. After 36 mos of follow-up in MM4, the OS HR shows a trend that favors the pbo arm. Because interim analyses of OS may be overrepresented by deaths in patients who did not benefit from maintenance therapy, it is not known to what extent these results will be reflective of the ITT population at the time of the final analyses. As treatment options, including anti-CD38 mAb and other new mechanisms of action, for salvage therapies following progression continue to expand, OS is increasingly being confounded by subsequent therapies. Hence, demonstrating OS advantage for early line MM therapies is becoming increasingly challenging. OS data continue to be collected in these studies for later analyses. Figure 1 Figure 1. Disclosures Dimopoulos: Takeda: Honoraria; Amgen: Honoraria; Beigene: Honoraria; Janssen: Honoraria; BMS: Honoraria. Lonial: AMGEN: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Merck: Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Chng: Johnson and Johnson: Honoraria, Research Funding; BMS/Celgene: Honoraria, Research Funding; Takeda: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Iida: Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Chugai: Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Glaxo SmithKlein: Research Funding; Amgen: Research Funding; Abbvie: Research Funding; Bristol-Myers Squibb: Research Funding. Mateos: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Oncopeptides: Honoraria. Morgan: BMS: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Kumar: Takeda: Current Employment, Current holder of stock options in a privately-held company. Suryanarayan: Takeda: Current Employment. Vorog: Takeda: Current Employment. Fergus: Takeda: Current Employment. Labotka: Takeda: Current Employment. OffLabel Disclosure: Use of the oral proteasome inhibitor ixazomib as maintenance treatment for multiple myeloma following stem cell transplantation or induction therapy in newly diagnosed patients.

Abstract Background: SUMOylation, a post-translational modification analogous to ubiquitination, attaches a small, ubiquitin-like modifier (SUMO) to target proteins. SUMOylation plays a central role in the immune system by regulating type I interferon (IFN-I) expression, thereby functioning to constrain the innate immune response (Decque Nat Immunol 2016), and limit tumor immune surveillance. The SUMOylation pathway is often overexpressed in multiple myeloma (MM) and is associated with poor outcomes (Driscoll Blood 2010). TAK-981 is a first-in-class, small-molecule inhibitor of SUMO-activating enzyme, which blocks the SUMOylation cascade (Langston J Med Chem 2021) and increases IFN-I production and signaling in innate immune cells (Nakamura AACR 2019). In ex vivo assays, TAK-981 activated the IFN-I pathway, increased phagocytic activity of monocyte-derived macrophages, and increased natural killer (NK) cell cytotoxicity via IFN-I signaling (Nakamura AACR 2019). The ability of TAK-981 to promote activation of macrophages and NK cells provides a mechanistic rationale for its use in combination with monoclonal antibodies (mAbs) reliant on antibody-dependent cellular cytotoxicity and phagocytosis; in vivo experiments have demonstrated synergistic activity between TAK-981 and rituximab, and between TAK-981 and the anti-CD38 mAbs daratumumab (dara) (Nakamura SITC 2020) or mezagitamab (meza; TAK-079; Figure 1). Patients with MM who have disease refractory to the three most effective classes of anti-myeloma therapies (proteasome inhibitors [PIs], immunomodulatory drugs [IMiDs], and anti-CD38 mAbs) have a poor prognosis, with median survival 9.2 months (Gandhi Leukemia 2019). Given the incurable nature of advanced MM and the highly complex mechanisms of resistance, continued efforts to better understand MM biology at the time of relapse and to translate this into effective treatment combinations are needed. Combination therapies that engage the immune system to treat MM may offer substantial clinical benefit. Methods: To be eligible for this multicenter, open-label, Phase 1b/2 trial (NCT04776018), patients must have failed at least 3 prior lines of anti-myeloma therapy, have MM disease that is triple-class refractory (defined as refractory/intolerant to ≥1 PI and ≥1 IMiD, and refractory to ≥1 anti-CD38 mAb), and have demonstrated disease progression on their last therapy. Prior CAR-T therapy is allowed. Patients will be assigned to TAK-981 plus subcutaneous (SC) meza (Phase 1 Part 1) or SC dara (dara and hyaluronidase-fihj; Phase 1 Part 2). The primary objectives of Phase 1b are to determine safety and tolerability, and to select the recommended Phase 2 dose (RP2D) and schedule for TAK-981 with each mAb; secondary objectives are to evaluate preliminary antitumor activity, to characterize TAK-981 pharmacokinetics (PK), and to explore pharmacodynamic (PD) markers of TAK-981 target engagement and SUMOylation pathway inhibition. Approximately 30 patients will participate in the Phase 1b Part 1 dose escalation of TAK-981 plus meza (~15 patients per dosing schedule), and ~15 patients will participate in the Phase 1b Part 2 dose escalation of TAK-981 plus SC dara. The primary objective of Phase 2 is to evaluate the efficacy of TAK-981 at the RP2D in combination with an anti-CD38 mAb; ~36 patients will be enrolled. In Phase 1b, patients will receive TAK-981 via a 1-hour intravenous infusion either on days 1, 4, 8, 11, and 15 (twice weekly; BIW) or on days, 1, 8, 15, and 22 (weekly; QW) for 2x 28-day cycles, then 8x every other week, then monthly. Meza 600 mg SC or dara 1800 mg SC will be given 8x weekly, 8x every other week, then monthly, in a 28-day cycle (Figure 2). Treatment will continue until disease progression or unacceptable toxicity (max. 24 cycles). TAK-981 dose escalation will proceed from 60 mg BIW, a dose shown to be pharmacologically active in a first-in-human, single-agent TAK-981 study (TAK-981-1002; data on file). Dose escalation will be guided by Bayesian Optimal Internal Design with Informative Prior (iBOIN) plus consideration of other safety, clinical, PK, and PD data. The iBOIN design selects the true maximum tolerated dose (if any) with high accuracy by allocating more patients to dose levels with a prior dose-limiting toxicity probability closest to the target of 0.3. This study is currently enrolling patients, with the first patient dosed in May 2021. Figure 1 Figure 1. Disclosures Lonial: AMGEN: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Research Funding; Merck: Honoraria; Abbvie: Consultancy, Honoraria. Boccia: BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Morphosis: Honoraria, Speakers Bureau. Yimer: Beigene: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau; Janssen: Speakers Bureau; GSK: Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Texas Oncology: Current Employment. Levy: Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Dova: Consultancy, Other: Promotional speaker; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; GSK: Consultancy, Other: Promotional speaker; Epizyme: Consultancy, Other: Promotional speaker; Novartis: Consultancy, Other: Promotional speaker; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau. Abonour: Takeda: Research Funding; GSK: Consultancy, Honoraria, Research Funding; Celgene-BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jensen: Honoraria, Research Funding. Mohan: Medical College of Wisconsin: Current Employment. Girnius: BMS: Honoraria, Speakers Bureau; Celgene: Speakers Bureau; Genentech: Honoraria; GSK: Honoraria, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Speakers Bureau. Rosenbaum: Takeda: Honoraria; Akcea: Honoraria; Janssen: Honoraria. Nadeem: Karyopharm: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Berg: Takeda: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Chao: Takeda: Current Employment. Berger: Takeda Development Center Americas, Inc.: Current Employment. Nakamura: Takeda Development Center Americas, Inc.: Current Employment. Zhang: Takeda: Current Employment. Song: Takeda Pharmaceuticals International Co.: Current Employment. Ward: Takeda: Current Employment. Proscurshim: Takeda Pharmaceuticals: Current Employment, Current holder of individual stocks in a privately-held company. Kumar: Novartis: Research Funding; Tenebio: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Beigene: Consultancy; Bluebird Bio: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Oncopeptides: Consultancy; Amgen: Consultancy, Research Funding; Carsgen: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. OffLabel Disclosure: Study of the investigational agent TAK-981 in combination with daratumumab and hyaluronidase-fihj or the investigational agent mezagitamab (TAK-079).

Abstract Introduction: Depth of response is associated with long-term outcomes in multiple myeloma (MM); however, the effect of response kinetics on outcomes in NDMM is variable and less clear. Although some studies have shown that achieving a ≥very good partial response (VGPR) at 4 months (mos) from diagnosis is associated with increased overall survival (Garderet Leukemia 2018), other reports have shown worse outcomes in pts with early vs late responses (Yan Blood Adv 2019). The double-blind, randomized TOURMALINE-MM2 (NCT01850524) trial (Facon Blood 2021) showed a clinical meaningful progression-free survival (PFS) benefit with IRd vs pbo-Rd (median 35.3 vs 21.8 mos; hazard ratio, 0.830; 95% confidence interval, 0.676-1.018; P=0.073; median follow-up, 53.3 and 55.8 mos, respectively) in NDMM pts. Safety data were consistent with the established toxicity profile of IRd. We evaluated PFS and duration of response (DOR) by depth of best confirmed response and time to best response in TOURMALINE-MM2. Methods: Pts were randomized to receive oral ixazomib 4 mg (n=351) or placebo (n=354) on days 1, 8, and 15, plus oral lenalidomide 25 mg (10 mg if creatinine clearance ≤60 mL/min) on days 1-21 and oral dexamethasone 40 mg (20 mg in pts aged >75 years) on days 1, 8, 15, and 22 in 28-day cycles. After 18 cycles, treatment was continued without dexamethasone and reduced doses of ixazomib (3 mg) and lenalidomide (10 mg) until progressive disease (PD)/toxicity. Response assessments were performed every cycle until PD, or every 4 weeks in pts who discontinued treatment prior to PD. PFS and DOR were analyzed post-hoc in subgroups defined by depth of response and in subgroups defined by time to best confirmed response; 'early' and 'late' responses were defined by time to best confirmed response of 0-4 and >4 mos, respectively (additional analyses were performed by time to best confirmed response of 0-6 and >6 mos). Pts in either subgroup could have recorded an initial response prior to their best response. PFS and DOR were evaluated from randomization to progression and time of initial response to progression, respectively. To address potential guarantee-time bias in the PFS analysis, and to eliminate potential bias due to transient responses in DOR analysis, sensitivity analyses were conducted in pts with PFS / DOR of ≥6 mos. Results: Among the 705 pts in the intention-to-treat (ITT) population, 20% (26% IRd vs 14% placebo-Rd) had a best confirmed response of complete response (CR) or stringent CR, 35% (37 vs 34%) had VGPR, 26% (19 vs 32%) had PR, 10% (9 vs 10%) had stable disease (SD), 3% (1 vs 4%) had PD. 7% (8 vs 6%) of pts were not evaluable. In a pooled analysis of both arms, achieving a deeper response was associated with longer PFS (Figure, A) and DOR (median not reached [NR], 42.8, and 15.0 mos for pts with ≥CR, VGPR, and PR, respectively). In 570 pts with ≥PR (288 IRd; 282 pbo-Rd), 152 (53%) and 136 (47%) in the IRd arm and 143 (51%) and 139 (49%) pts in the pbo-Rd arm were defined as early (0-4 mos) and late (>4 mos) responders, respectively. For early vs late responders, 46% vs 40% were aged ≥75 years, 21% vs 12% had International Staging System stage III MM, and 44% vs 33% had expanded high-risk cytogenetic abnormalities. Median PFS was prolonged among late vs early responders with IRd (65.7 vs 21.2 mos) and pbo-Rd (62.6 vs 18.2 mos), as was median DOR (IRd, NR vs 22.6 mos; pbo-Rd, 64.1 vs 17.2 mos). The PFS sensitivity analysis among pts with PFS of ≥6 mos confirmed the association of late response with improved outcomes; among late vs early responders achieving ≥PR, median PFS was 65.7 vs 23.9 mos with IRd and 62.6 vs 18.4 mos with pbo-Rd (Figure, B), and among late vs early responders achieving ≥VGPR, median PFS was 65.7 vs 35.3 mos with IRd and 64.4 vs 21.7 with pbo-Rd. Conclusions: Achieving a deeper response was associated with prolonged PFS and DOR in NDMM patients in TOURMALINE-MM2. PFS benefit on the ITT analysis was driven by the higher rates of deep responses (≥VGPR) with IRd vs pbo-Rd. PFS and DOR were also longer in pts achieving a late vs early best confirmed response of ≥PR or ≥VGPR. Consistent with results from a similar analysis in relapsed/refractory MM in the TOURMALINE-MM1 trial (Garderet Leukemia 2018), our findings support the continuation of therapy with the aim of achieving a deeper response over time. Additional sensitivity analyses will be presented. Figure 1 Figure 1. Disclosures Richardson: Sanofi: Consultancy; AstraZeneca: Consultancy; Celgene/BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; Oncopeptides: Consultancy, Research Funding; Protocol Intelligence: Consultancy; Secura Bio: Consultancy; Janssen: Consultancy; Takeda: Consultancy, Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding. Venner: Takeda: Honoraria; BMS: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; GSK: Honoraria. Bahlis: GlaxoSmithKline: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Genentech: Consultancy; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. White: Amgen: Consultancy, Honoraria; Antengene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Forus: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Karlin: Celgene-BMS: Honoraria, Other: member of advisory board; Sanofi: Honoraria; oncopeptide: Honoraria; Janssen: Honoraria, Other: member of advisory board, travel support; Abbvie: Honoraria; GSK: Honoraria, Other: member of advisory board; Amgen: Honoraria, Other: travel support and advisory board ; Takeda: Honoraria, Other: member of advisory board. Rigaudeau: Takeda: Membership on an entity's Board of Directors or advisory committees. Suzuki: Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; ONO: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Abie: Honoraria; Janssen: Consultancy, Honoraria. Shibayama: Mundi Pharma: Honoraria; Otsuka: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Nippon Shinyaku: Honoraria; Fujimoto: Honoraria; Daiichi Sankyo: Honoraria; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Essentia Pharma Japan: Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Avvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Celgene: Research Funding. Zhang: Takeda: Current Employment. Kumar: Takeda: Current Employment, Current holder of stock options in a privately-held company. Twumasi-Ankrah: Takeda: Current Employment. Labotka: Takeda: Current Employment. Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Fresenius-Kabi: Membership on an entity's Board of Directors or advisory committees; Coherus: Membership on an entity's Board of Directors or advisory committees; McKesson: Current Employment, Current equity holder in publicly-traded company; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb (Celgene): Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Lonial: AMGEN: Consultancy, Honoraria; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Honoraria. Kumar: Antengene: Consultancy, Honoraria; Carsgen: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; Roche-Genentech: Consultancy, Research Funding; Novartis: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Moreau: Amgen: Honoraria; Oncopeptides: Honoraria; Janssen: Honoraria; Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria. OffLabel Disclosure: Use of the oral proteasome inhibitor ixazomib in newly diagnosed multiple myeloma patients who are ineligible for transplant.

Abstract Introduction Systemic immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys. Management of the disease relies primarily on off-label use of multiple myeloma therapies. No treatments are approved for AL amyloidosis in the relapsed/refractory setting. In the phase 3, open-label TOURMALINE-AL1 trial (NCT01659658), patients with relapsed/refractory AL amyloidosis were randomized 1:1 to receive either oral ixazomib plus dexamethasone (Id) or physician's choice (CH) in 28-day cycles, and followed until progression or unacceptable toxicity. An interim analysis demonstrated that Id was well tolerated and, although the primary endpoint of hematologic response rate was not met, time-to-event efficacy analyses consistently favored Id. We report an analysis of patient-reported outcome (PRO) data on health-related quality of life (HRQOL) and AL amyloidosis symptoms from TOURMALINE-AL1; such data for AL amyloidosis in general have been limited. Methods Four PRO instruments were used to collect data to support PRO-related secondary endpoints during the treatment period: the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG-Ntx), an amyloidosis symptom questionnaire (ASQ), the EuroQoL 5-Dimension 3-Level (EQ-5D-3L), and the Visual Analogue Scale (EQ VAS) were collected at screening, day 1 of each cycle, and end of treatment (EOT), and the 36-item Short Form General Health Survey version 2 (SF-36v2) was collected at screening, day 1 of every third cycle, and EOT. Analysis of PRO data included descriptive summaries of means and change from baseline and a linear mixed model (LMM) for repeated measures for patients in the intent-to-treat (ITT) population with a baseline and at least one postbaseline PRO-specific assessment. No adjustment was made for multiple comparisons. Data cutoff date was 20 February 2019. Results The ITT population included 168 patients (Id: n=85; CH: n=83), who completed up to 58 cycles (Id) and up to 43 cycles (CH); median treatment duration was 11.7 vs 5.0 months, respectively. PRO compliance in the treatment period was high for all instruments (Figure). Baseline HRQOL as measured by the SF-36v2 and EQ VAS was similar between treatment arms. During the treatment period, SF-36v2 Mental and Physical Component Summary (MCS and PCS) scores remained stable relative to baseline and were similar between arms; the 8 subscale scores were also generally maintained over time, and mostly similar between arms. Least-squares (LS) mean changes from baseline were significantly higher (better HRQoL) for Id compared with CH at several cycles in the SF-36v2 Role Physical and Vitality subscales (p<0.05) (Figure); no subscales demonstrated significant differences favoring CH. Symptom burden as measured by the FACT/GOG-Ntx and ASQ was low at baseline, leaving little room for improvement. FACT/GOG-Ntx scores were generally maintained over time. In the treatment period, there were small but significant differences in LS mean changes from baseline favoring Id over CH at multiple cycles for 7 of the 11 individual items and the neurotoxicity and sensory summary scores; there were small but significant differences favoring CH over Id for 1 individual item (trouble hearing) at a few later cycles. The ASQ total score trended downward slightly (lower burden) during treatment after the first few cycles in both arms. There were significant differences per the LMM favoring Id over CH at cycles 7 and 21 (p<0.05). In both arms, EQ VAS scores trended upward (better HRQoL) during treatment and then declined slightly at EOT. (LMM analyses were not conducted for EQ-5D.) At EOT, a slight deterioration from baseline was observed in actual scores for SF-36v2 domains and summary scales, FACT/GOG-Ntx neurotoxicity and sensory subscales, and ASQ items and total score for both Id and CH. Conclusions Relapsed/refractory AL amyloidosis patients treated with Id experienced HRQOL and symptoms that were similar to or trended better than patients treated with CH. These data suggest that treatment with Id, although with a substantially longer treatment duration, did not have a negative impact on HRQOL in patients with relapsed/refractory AL amyloidosis, a population with currently no approved treatment options. Figure 1 Figure 1. Disclosures Sanchorawala: Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Pfizer: Honoraria; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Prothena: 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; Takeda: Research Funding; Celgene: Research Funding. Wechalekar: Caelum Biosciences: Other: Clinical Trial Funding; Alexion, AstraZeneca Rare Disease: Consultancy; Janssen: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria. Kim: Janssen, BMS: Research Funding. Schönland: Janssen: Honoraria, Other: Travel grants, Research Funding; Takeda: Honoraria, Other: Travel grants; Sanofi: Research Funding; Prothena: Honoraria, Other: Travel grants; Pfizer: Honoraria. Landau: Takeda, Janssen, Caelum Biosciences, Celgene, Pfizer, Genzyme: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Genzyme: Honoraria. Fiona: Pfizer: Research Funding. Suzuki: Janssen: Consultancy, Honoraria; Abie: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; ONO: Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Dispenzieri: Sorrento Therapeutics: Consultancy; Oncopeptides: Consultancy; Pfizer: Research Funding; Alnylam: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Comenzo: Karyopharm: Research Funding; Takeda: Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Janssen: Patents & Royalties: WO2016187546A1, Research Funding; Prothena Biosciences: Consultancy, Research Funding; Caelum: Consultancy, Research Funding. Cherepanov: Takeda: Current Employment, Current equity holder in publicly-traded company. Hayden: Takeda: Current Employment, Current equity holder in publicly-traded company. Kumar: Takeda: Current Employment, Current holder of stock options in a privately-held company. Labotka: Takeda: Current Employment. Faller: Takeda Pharmaceuticals Co.: Current Employment; Viracta Therapeutics, Inc: Current holder of stock options in a privately-held company, Ended employment in the past 24 months, Membership on an entity's Board of Directors or advisory committees; Briacell, Inc: Current holder of stock options in a privately-held company. Kastritis: Amgen, Genesis Pharma, Janssen, Takeda: Consultancy; Amgen, Janssen, Pfizer: Research Funding; Amgen, Genesis Pharma, Janssen, Takeda, Pfizer: Honoraria.