Citations

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

SummaryIn young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front‐line setting. Recently, time‐to‐event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post‐autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six‐month [hazard ratio (HR) = 7·68], 12‐month (HR = 6·68), and 18‐month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non‐relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high‐risk group with inferior post‐relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up‐front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

Abstract Purpose: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non–Hodgkin lymphomas with aggressive clinical behavior. We performed comprehensive miRNA profiling in PTCLs and corresponding normal CD4+ Th1/2 and TFH-like polarized subsets to elucidate the role of miRNAs in T-cell lymphomagenesis. Experimental Design: We used nCounter (NanoString Inc) for miRNA profiling and validated using Taqman qRT-PCR (Applied Biosystems, Inc). Normal CD4+ T cells were polarized into effector Th subsets using signature cytokines, and miRNA significance was revealed using functional experiments. Results: Effector Th subsets showed distinct miRNA expression with corresponding transcription factor expression (e.g., BCL6/miR-19b, -106, -30d, -26b, in IL21-polarized; GATA3/miR-155, miR-337 in Th2-polarized; and TBX21/miR-181a, -331-3p in Th1-polarized cells). Integration of miRNA signatures suggested activation of TCR and PI3K signaling in IL21-polarized cells, ERK signaling in Th1-polarized cells, and AKT–mTOR signaling in Th2-polarized cells, validated at protein level. In neoplastic counterparts, distinctive miRNAs were identified and confirmed in an independent cohort. Integrative miRNA–mRNA analysis identified a decrease in target transcript abundance leading to deregulation of sphingolipid and Wnt signaling and epigenetic dysregulation in angioimmunoblastic T-cell lymphoma (AITL), while ERK, MAPK, and cell cycle were identified in PTCL subsets, and decreased target transcript abundance was validated in an independent cohort. Elevated expression of miRNAs (miR-126-3p, miR-145-5p) in AITL was associated with poor clinical outcome. In silico and experimental validation suggest two targets (miR-126→ SIPR2 and miR-145 → ROCK1) resulting in reduced RhoA-GTPase activity and T–B-cell interaction. Conclusions: Unique miRNAs and deregulated oncogenic pathways are associated with PTCL subtypes. Upregulated miRNA-126-3p and miR-145-5p expression regulate RhoA-GTPase and inhibit T-cell migration, crucial for AITL pathobiology.

SummaryZUMA‐1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi‐cel), an autologous CD19‐directed chimaeric antigen receptor (CAR)‐T cell therapy, in refractory large B‐cell lymphoma. To reduce treatment‐related toxicity, several exploratory safety management cohorts were added to ZUMA‐1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end‐points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days −5 through −3), 2 × 106 CAR‐T cells/kg (day 0) and once‐daily oral dexamethasone [10 mg, day 0 (before axi‐cel) through day 2]. Forty patients received axi‐cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty‐eight per cent of patients did not experience CRS or NEs within 72 h of axi‐cel. With a median follow‐up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

AbstractThis phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

Abstract Introduction Brentuximab vedotin (BV) is an ADC directed against CD30, a receptor expressed by malignant Reed-Sternberg (RS) cells present in the inflammatory/immune cell microenvironment of classical Hodgkin lymphomas (cHL). Through induction of immunogenic cell death, BV may prime an antitumor immune response via microtubule disruption of CD30-expressing RS cells (Gardai 2015). Tumor cells expressing PD-1 ligands use the PD-1 pathway to evade an immune response. Nivolumab (Nivo) blocks the PD-1 receptor, inhibits binding of PD-1 ligands, and restores an effective antitumor immune response. Targeted killing of CD30-expressing RS cells, concurrent with restoration of the immune response, may lead to higher complete response (CR) rates in patients (pts) with relapsed or refractory cHL (R/R HL), as well as improved durability of responses post autologous stem cell transplant (ASCT). Here we present updated results from the phase 1/2 study of BV + Nivo in pts with R/R HL. Methods BV + Nivo was evaluated in cHL that had relapsed or was refractory to frontline (FL) chemotherapy in adult pts (NCT02572167). Pts were excluded if they had received prior salvage therapy, BV or immuno-oncology therapy, or allogeneic SCT or ASCT. Pts were treated in 21-day cycles for up to 4 cycles. In Parts 1 and 2 of the trial, BV (1.8 mg/kg) was given on Cycle 1 Day 1 and Nivo (3 mg/kg) on Cycle 1 Day 8. For Cycles 2-4, BV and Nivo were given on Day 1. After the Cycle 4 response assessment, pts were eligible to undergo ASCT. The investigators assessed response per the Lugano Classification (Cheson 2014). Results 62 pts with R/R HL were enrolled in Parts 1 and 2; 61 pts received BV + Nivo, of whom 58 completed treatment (tx). 4 pts discontinued the study due to pt decision (2), AE (1), and investigator decision (1). Median age was 36 years, 52% were female, and 90% had received FL ABVD. 45% of pts had primary refractory disease and 31% experienced relapse within 1 year of FL therapy. Infusion-related reactions (IRRs) occurred in 41% of pts. Tx emergent AEs occurred in 98% of pts prior to ASCT (33% G3, 5% G4). Excluding IRRs, potential immune-related AEs (IrAEs) occurred in 84% of pts (10% G3, 3% G4) with 5 pts (8%) treated with systemic steroids for G4 pneumonitis, G4 pneumonitis and colitis, G2 pneumonitis, G3 diarrhea and G2 colitis, and G3 AST elevation. Among the 60 efficacy-evaluable pts, the CR rate was 62%, (48% of CR pts had Deauville ≤ 2) with an objective response rate of 85%; 5 pts (8%) had stable disease and 4 pts (7%) progressed on tx. At the time of this analysis, 39 pts had initiated ASCT with a median 5.1x106 CD34+ cells/kg (range; 3-60) collected. Median times to neutrophil and platelet engraftment were 12 and 15 days, respectively. Pts were followed for a median of 3 months from ASCT (N=39, range; 0-12) and 5.7 months from first dose (N=61, range; 1-17). BV and Nivo effects on the immune system were evaluated by peripheral blood immunophenotyping, serum cytokine/chemokine analyses, T-cell receptor sequencing, and intracellular cytokine staining. The first dose of BV resulted in elevation of pro-inflammatory cytokines and chemokines and concurrent reduction in serum TARC levels, with these results maintained post Nivo. We observed a reduction in Tregs and other T cell subsets after the first dose of BV with an elevation of T cell subsets post BV + Nivo. While TCR clonality in the periphery did not change over the course of the trial, T cell clonal expansion was observed post BV + Nivo, concurrent with T cell elevation measured by flow cytometry. Ex vivo peptide stimulation of PBMCs isolated from blood revealed the enhanced ability of T cell subsets to respond to MHC I and MHC II antigens following BV + Nivo compared to baseline: e.g., effector memory CD8+ T cells from some pts displayed increased intracellular IL-2, and TNFa after stimulation with MHCI and MHCII peptide pools compared to baseline, potentially indicating elevated activation status of the immune system following combination tx. Conclusion R/R HL remains an unmet clinical need despite recent medical advances. These data suggest the combination BV + Nivo is a well tolerated and an active salvage therapy with a high rate of CR (62%) that has no adverse impact on stem cell collection. The safety and activity of this novel combination support further exploration in an ongoing pivotal phase 3 trial in pts with R/R HL who have either already received or are considered ineligible for ASCT (NCT03138499). Disclosures Herrera: Seattle Genetics: Research Funding; Merck: Consultancy; Genentech: Consultancy; BMS: Consultancy; Pharmacyclics: Consultancy. Moskowitz: Seattle Genetics: Honoraria, Research Funding; Takeda: Honoraria; Incyte: Research Funding; ADC Therapeutics: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding. Bartlett: Novartis: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Millenium: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Affimed: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Bristol-Meyers Squibb: Research Funding; Merck & Co: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Vose: Merck: Research Funding; Kite: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Allos Therapeutics: Research Funding; Acerta: Research Funding; Incyte: Research Funding; Onyx: Research Funding; Seattle Genetics: Research Funding; US Biotest: Research Funding; Bristol-Myers Squibb: Research Funding. Ramchandren: Seattle Genetics: Consultancy; MERCK: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding. Feldman: AbbVie: Speakers Bureau; Janssen: Speakers Bureau; Kite Pharma: Speakers Bureau; Celgene: Speakers Bureau; Pharmacyclics: Speakers Bureau; Seattle Genetics: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy. LaCasce: BMS: Consultancy; Forty Seven: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding. Ansell: Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Celldex: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding. Moskowitz: Celgene: Consultancy; Seattle Genetics: Consultancy, Other: Ad Board, Research Funding; Genentech BioOncology: Consultancy; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding. Fenton: Seattle Genetics: Employment, Equity Ownership. Ogden: Seattle Genetics: Employment, Equity Ownership. Taft: Seattle Genetics: Employment, Research Funding. Zhang: Seattle Genetics: Employment, Research Funding. Kato: Bristol-Myers Squibb: Employment, Equity Ownership; Seattle Genetic: Research Funding. Campbell: Seattle Genetics: Employment, Equity Ownership; CTI BioPharma: Employment, Equity Ownership. Advani: Agensys: Research Funding; Pharmacyclics: Research Funding; Regeneron: Research Funding; FortySeven: Research Funding; Nanostring: Consultancy; Celgene: Research Funding; Pharmacyclics: Consultancy; Merck: Research Funding; Juno Therapeutics: Consultancy; Kura: Research Funding; Janssen: Research Funding; Millennium: Research Funding; Seattle Genetics: Research Funding; Gilead: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Spectrum: Consultancy; Bayer Healthcare Pharmaceuticals: Research Funding; Infinity: Research Funding; Genentech: Research Funding; Cell Medica: Research Funding; Sutro: Consultancy.

Background: Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is approved for treatment of adult pts with R/R LBCL after ≥ 2 lines of systemic therapy. In the pivotal ZUMA-1 study, axi-cel demonstrated durable responses and a largely manageable safety profile (Locke FL, et al. Lancet Oncol. 2019). ZUMA-9 (NCT03153462), a multicenter, open-label study, provided pts with R/R LBCL with expanded access to axi-cel until commercial availability (Cohort 1 [C1]) and later, if commercially manufactured product did not meet commercial release specification(s) (Cohort 2 [C2]). Safety and efficacy of axi-cel (C1 and C2) and translational analyses (C2) are presented. Methods: Eligible adults had histologically confirmed R/R LBCL, ECOG ≤ 1, and received prior CD20-targeting and an anthracycline-containing regimen. C2 pts must have had commercial OOS product. Pts underwent leukaphersis and conditioning chemotherapy (cyclophosphamide 500 mg/m2/day and fludarabine 30 mg/m2/day) for 3 days followed by a single axi-cel infusion (target dose, 2 × 106 CAR T cells/kg). C1 and C2 pts with high disease burden could receive bridging therapy before conditioning at investigator's discretion. Endpoints included frequency of adverse events (AEs), objective response rate (ORR) per standard-of-care imaging assessment, overall survival (OS) for C1 and C2, and blood CAR T cells levels and serum cytokines for C2 only. Outcomes were contextualized with the primary analysis of ZUMA-1 C1+2 (n = 101; ≥ 6 mo of follow-up; Neelapu SS, et al. NEJM. 2017). Results: As of 11/29/2019 (C1) and 3/15/2020 (C2), 25 C1 pts and 36 C2 pts received axi-cel with a median follow-up of 27.1 mo (range, 23.6 - 29.6) and 13.2 mo (range, 0.4 - 25.7), respectively. In C1, median age was 56 y (range, 28 - 76), 60% were male, 80% had DLBCL, 48%/0% had ECOG1/≥2, 44% had IPI ≥3, and 64% had ≥ 3 prior lines of therapy. In C2, median age was 61 y (range, 24 - 81), 75% were male, 78% had DLBCL, 58%/17% had ECOG 1/≥2, 56% had IPI ≥3, and 69% had ≥ 3 prior lines of therapy. In C2, 50% of pts had OOS product with low viability, 28% had high IFN-γ, 14% had low IFN-γ, 14% received a low dose, and 6% had high transduction ratio. The ORR was 76% (64% complete response [CR]) for C1, 53% (36% CR) for C2, and 82% (54% CR) for ZUMA-1 C1+2. Median OS was 23.8 mo (95% CI, 13.5 - NE) for C1 and not reached (95% CI, 3.4 - NE) for C2, respectively. ORR and OS were consistent in C2 OOS subgroups (Table). Grade ≥ 3 AEs were reported in 88% and 89% of C1 and C2 pts, respectively. Grade ≥ 3 CRS (Lee et al, Blood. 2014) was not observed in C1 but was reported in 3% of C2 pts (13% in ZUMA-1 C1+2). Grade ≥ 3 neurologic events (NEs) occurred in 36% and 19% of pts in C1 and C2, respectively, and 28% of pts in ZUMA-1 C1+2. No Grade 5 CRS or NEs occurred in C1 or C2. All CRS and NEs resolved in C1, and most CRS (29/30) and NEs (19/24) resolved in C2 as of the data cutoff. Of 3 Grade 5 AEs in C1, 2 were unrelated to axi-cel (clostridial sepsis [on Day (D) 6] and respiratory failure [on D212]) and 1 was related to conditioning (myelodysplastic syndrome [on D563]). Of 3 Grade 5 AEs in C2, 2 were unrelated to axi-cel (multiple organ dysfunction syndrome [on D6] and cardiac arrest [on D482]) and 1 was related to axi-cel (systemic mycosis [on D30]). Median peak CAR T cell levels and median CAR T cell expansion (area under the curve in the first 28 days) were lower in ZUMA-9 C2 (n = 32/36; 12 cells/µL [range, 0 - 442] and 112 cells/µL × days [range, 0 - 3413]) vs ZUMA-1 C1+2 (n = 96/101; 42 cells/µL [range, 1 - 1514] and 462 cells/µL × days [range, 5 - 14,329]). Serum IFN-γ levels peaked within 8 days after axi-cel infusion (median, 170 pg/mL [range, 8 - 1876]) and were lower vs ZUMA-1 C1+2 (median, 477 pg/mL [range, 8 - 8209]). Axi-cel in ZUMA-9 C2 contained fewer, less differentiated CCR7+ naïve and central memory T cells, and a greater proportion of more differentiated CCR7- effector memory and effector T cells vs ZUMA-1 C1+2. No cases of replication-competent retroviruses were reported in C1 or C2. Conclusion: Axi-cel treatment demonstrated a manageable safety profile and meaningful clinical benefit in this expanded access and OOS product study. While CAR T cell therapy showed clinical benefit in C2 (OOS product), the lower CR rate was corroborated by lower CAR T cell expansion and a more differentiated product vs ZUMA-1 C1+2, warranting further investigation. ZUMA-9 C2 is enrolling pts and evaluation is ongoing. Disclosures Jacobson: Precision Biosciences: Consultancy, Honoraria, Other: travel support; Celgene/BMS: Consultancy, Honoraria, Other: travel support; Novartis: Consultancy, Honoraria, Other: travel support; AXIS: Speakers Bureau; Nkarta: Consultancy, Honoraria, Other: travel support; Clinical Care Options: Speakers Bureau; Pfizer: Research Funding; Lonza: Consultancy, Honoraria, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: travel support. Locke:Calibr: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Wugen: Consultancy; GammaDelta Therapeutics: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Cellular Biomedicine Group: Other: Consultancy with grant options; Allogene: Consultancy. Miklos:Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding; Miltenyi Biotec: Research Funding; Janssen: Consultancy, Other: Travel support; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Vose:Incyte: Research Funding; Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Allogene: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Miltenyi Biotec: Honoraria; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Kite, a Gilead Company: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Verastem: Consultancy, Honoraria; Wugen: Honoraria; Celgene: Honoraria; Roche/Genetech: Consultancy, Honoraria, Other. Lin:Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Vineti: Consultancy; Gamida Cells: Consultancy; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding. Budde:Roche: Consultancy; Merck: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Consultancy; Gilead Sciences: Consultancy; Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding. Maloney:Celgene: Consultancy, Honoraria, Research Funding; A2 Biotherapeutics: Consultancy, Current equity holder in publicly-traded company, Honoraria; Gilead Sciences: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Patents are pending, but not issued, licensed, no royalties, no licensees., Research Funding; Bioline Rx: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Jaglowski:Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy; Novartis: Consultancy, Research Funding. Riedell:MorphoSys: Research Funding; Kite/Gilead: Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Karyopharm Therapeutics: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding. Perales:Celgene: Honoraria; MolMed: Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Research Funding; Miltenyi Biotec: Research Funding; Merck: Consultancy, Honoraria; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: 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; Cidara Therapeutics: Other; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Medigene: Membership on an entity's Board of Directors or advisory committees, Other; NexImmune: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Honoraria, Research Funding. Kim:Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Kawashima:Kite, a Gilead Company: Current Employment; Gilead Sciences: Other: stock or other ownership . Yang:Kite, a Gilead Company: Current Employment. Rossi:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Goyal:Kite, a Gilead Company: Current Employment. Neelapu:Legend Biotech: Other; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Unum Therapeutics: Other, Research Funding; Adicet Bio: Other; Novartis: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Precision Biosciences: Other: personal fees, Research Funding; Poseida: Research Funding; Calibr: Other; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Karus Therapeutics: Research Funding; Cellectis: Research Funding; N/A: Other.