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Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) after AuSCT in pts with MM. Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAM F7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. We report updated results of this phase 2 trial evaluating the efficacy and safety of adding ELO to LEN as maintenance therapy post- AuSCT. Patients and Methods: Between 4/15/2015-1/27/2016, 27 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2, q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=73 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until disease progression (PD). LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity > grade 1 and significant cytopenias (ANC < 1000/mL, platelet count < 100,000/ml). For the 1st 8 weeks, pts The study's primary endpoint is PFS, defined as time from AuSCT to PD or death (whichever occurs first), or censored at date of last contact. Secondary objectives are best response, OS, incidence of second primary malignancies (SPMs) and adverse event (AE) profile. Total enrollment of 100 evaluable pts was completed on 6/5/2019. Patients are followed until death, withdrawal of consent or removal from study. Eligible pts received ≤2 lines of induction therapy, and were 60-210 days post-AuSCT. Results: Pts (n=100) have been treated for a median of 27.5 cycles (4-67). At study entry, 37 (37%) had complete response (CR), 40 (40%) very good partial response (VGPR), 22 (22%) partial response (PR) and 1 (1%) minor response (MR). Best response achieved to date on study is CR in 61 pts (61%), VGPR in 29 pts (29%) and PR in 10 pts (10%). Median time for conversion to CR on study is 1 month. Of pts in CR and tested for minimal residual disease (MRD) to date, 42/48 are negative (flow cytometry on ≥ 2 x106 cells). Eleven of 42 have converted from VGPR to MRD negative CR while on study. With a median follow up of 41 months, 90% of pts (n=90) remain alive. Eighteen pts have had PD; of these, 10 had high-risk cytogenetics. Three died of PD while receiving salvage therapy, 1 of pneumonia, 4 of second malignancies and 1 of unknown cause at another facility. One additional pt died on study in VGPR, after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Estimated 4 year PFS is 75%. High-risk cytogenetics (n =31) adversely affected PFS (p=0.01); 14/31 pts remain on study. Of 23 pts transitioned to another therapy, median 2nd PFS has not been reached. Grade 3-4 Hematologic AEs (no. of pts/102 pts) were: neutropenia 32% (33), febrile neutropenia 15% (15), thrombocytopenia 7% (7), and anemia 10% (10). Grade 3-4 non-Hematologic AEs (no. of pts): hypophosphatemia 29% (30), respiratory infections 21% (21), diarrhea 15% (15), fatigue 12% (12), peripheral neuropathy 8% (8), other infections 7% (7), myalgias 5% (5), dyspnea 5% (5). SPMs include cutaneous basal and squamous cell carcinomas (8), AML (1), B-cell ALL (1), t-MDS (4), osteosarcoma (1), intra-epidermal adenocarcinoma of the neck (1), mucinous appendiceal neoplasm (1), mucinous epidermoid carcinoma of parotid (1), prostate cancer (1). Renal cell carcinoma was diagnosed in 1 pt, 15 months after removal from study for PD. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy on which 38% of pts have had improvement in quality of response while on therapy, including 27% who converted to CR. SPM rates seem consistent with those observed in CALGB 100104 and IFM 2005-02 trials of lenalidomide alone. Longer follow up is required to determine how median PFS and OS will compare with those from lenalidomide monotherapy trials, and how SPM rates will continue to evolve. Table 1 Disclosures Thomas: X4 Pharma: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding. Shah:Karyopharm: Current Employment, Current equity holder in publicly-traded company. Lee:Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy. Manasanch:JW Pharma: Research Funding; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Glaxo Smith Kline: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Research Funding; Sanofi: Honoraria, Research Funding. Patel:Oncopeptides: Consultancy; Takeda: Consultancy, Research Funding; Cellectis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding. Kaufman:Bristol Myers Squibb: Research Funding; Karyopharm: Honoraria; Janssen: Research Funding. Iyer:Trillium: Research Funding; Daiichi Sankyo: Consultancy; Legend Biotech: Consultancy; Merck: Research Funding; Rhizen: Research Funding; Seattle Genetics, Inc.: Research Funding; Target Oncology: Honoraria; Afffimed: Research Funding; CRISPR: Research Funding; Spectrum: Research Funding; Curio Biosciences: Honoraria. Qazilbash:Angiocrine: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding; Bioline: Research Funding; Amgen: Research Funding. Bashir:Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding; Celgene: Research Funding; KITE: Other: Advisory Board. Orlowski:Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy. OffLabel Disclosure: Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against SLAM F7. It is FDA approved in combination with Lenalidomide and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. This is a phase 2 trial evaluating the efficacy and safety of adding ELO to LEN as maintenance therapy post-autologous stem cell transplant.

Background: Idiotypic determinants of the surface immunoglobulin (Ig) associated with a given pt's B-cell lymphoma are unique to that tumor, and can thus serve as a tumor-specific marker. This study aims to use an idiotype DNA vaccine to lengthen the smoldering phase of WM without inducing cross-resistance to available therapies. Administered vaccine used recombinant plasmid DNA encoding a fusion protein, consisting of autologous lymphoma scFv (pt-specific idiotype) and human CCL20 (macrophage inflammatory protein-3 alpha - MIP-3α) chemokine. Targeted delivery of this fusion protein to antigen-presenting cells, and subsequent processing and presentation, is hypothesized to break tolerance and generate an immune response against the idiotype, promoting eradication of antigen-expressing B-cell lymphoma cells. Methods: Pts with sWM received 3 intradermal vaccinations of pt-specific DNA vaccine at 4-week (wk) intervals (wks 0, 4 and 8). Two dose levels (500 µg; 2500 µg) were evaluated in a 3+3 design. The primary objective was to evaluate the vaccine's safety and identify the maximum tolerated dose. Secondary objectives were to assess immunogenicity of the vaccine to generate tumor-specific cellular immune responses. Results: Between 1/2016 - 1/2019, 9 pts (7 men) were treated (500 µg: n = 3; 2500 µg: n = 6). Median age at enrollment was 67 yrs (range 56-78); median time from diagnosis to 1st vaccination was 26.5 mos (8.8-120.9). MYD88 L265P + (6 pts). CXCR4 WHIM + (1 pt). With median follow up of 38 months (range: 8.8-51), 8 pts are known alive; 1 has been lost to follow up. Six have maintained stable disease; 3 have progressed to symptomatic WM at 8, 25, and 28 months respectively, from 1st vaccination). All pts completed planned therapy. No DLTs or Grade 4 AEs occurred. Ten mos. after the 3rd vaccination, 1 pt had a grade 3 pleural effusion and leukopenia with an increase in rheumatoid factor (23.1 IU/mL [normal range 0.0-15.9]) and ANA titer of 1:80; all resolved within 2 mos. Grade 1-2 AEs observed in > 3pts include: leukopenia (6), nausea (5), anemia (4), increased creatinine (4), fatigue (4). Immune correlatives have now been completed in all 9 patients. Analysis is ongoing, and complete data will be presented at the meeting. Serial pre- and post- vaccine samples analyzed by single-cell RNA seq from 3 representative patients (LPL 005, LPL 007, LPL 008) treated at the 2500 mg dose are shown in the Figure. DNA vaccine treatment significantly reduced the number of clonal B-cells in the bone marrow compartment of the 2 patients who have maintained SD (LPL 007 and LPL 008). DNA vaccine treatment also induced increases in monocytes in the tumor microenvironment of these 2 patients. In addition, T-cell receptor (TCR) sequence analysis revealed clear increases in TCR clonal expansions, consistent with a vaccine effect. In contrast, LPL 005, who had the earliest progression to symptomatic phase WM, had an increase in tumor B cells on post vaccine samples, and TCR clonotypes showed no changes. Similar changes were observed with serial bone marrow samples from the remaining patients treated on the trial, correlating with clinical outcome. Conclusions: Idiotype (scFv-CCL20) DNA vaccine therapy appears to be safe in pts with sWM. Preliminary results of serial single cell RNAseq analysis suggest that the tumor immune microenvironment is favorably altered after chemokine-tumor antigen DNA vaccine treatment and these vaccine-induced changes may correlate with clinical outcome. The immunologic changes observed suggest response to this vaccine, and warrant further investigation in a Phase II trial, possibly in combination with immune checkpoint blockade. Disclosures Thomas: Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Genentech: Research Funding; Pharmacyclics: Other: Advisory Boards; Xencor: Research Funding; X4 Pharma: Research Funding. Lee:GlaxoSmithKline: Consultancy, Research Funding; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Genentech: Consultancy; Sanofi: Consultancy; Genentech: Consultancy. Manasanch:Adaptive Biotechnologies: Honoraria; Glaxo Smith Kline: Honoraria; BMS: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Merck: Research Funding; JW Pharma: Research Funding; Novartis: Research Funding; Sanofi: Honoraria, Research Funding. Patel:Nektar: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Oncopeptides: Consultancy. Orlowski:Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; STATinMED Research: Consultancy; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees. Neelapu:Takeda Pharmaceuticals: Patents & Royalties; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; N/A: Other; Acerta: Research Funding; Karus Therapeutics: Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Unum Therapeutics: Other, Research Funding; Calibr: Other; Adicet Bio: Other; Legend Biotech: Other; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Precision Biosciences: Other: personal fees, Research Funding; Celgene: Other: personal fees, Research Funding; Novartis: Other: personal fees; Pfizer: Other: personal fees. Kwak:CJ Healthcare: Consultancy; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Xeme Biopharma/Theratest: Other: equity; Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. OffLabel Disclosure: This study aims to use a novel idiotype DNA vaccine to lengthen the smoldering phase of WM without inducing cross-resistance to available therapies.

Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) after myeloablative AuSCT in pts with MM. Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAM F7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of MM pts who have received 1-3 prior therapies. The objective of this phase 2 trial is to evaluate the efficacy and safety of adding ELO to LEN as maintenance therapy post-myeloablative AuSCT. We report updated results of the primary (PFS) and secondary (overall survival [OS] and toxicity) endpoints. Patients and Methods: Between 4/15/2015-1/27/2016, 27 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2, q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=57 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until disease progression (PD). LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity > grade 1 and significant cytopenias (ANC < 1000/mL, platelet count < 100,000/ml). For the 1st 8 weeks, pts The study's primary endpoint is PFS, defined as time from AuSCT to PD or death (whichever occurs first), or time of last contact. Secondary objectives are best response, OS, incidence of second primary malignancies (SPMs) and adverse event (AE) profile. Total enrollment of 100 pts is planned. Patients are followed until death, withdrawal of consent or removal from study. Eligible pts received ≤2 lines of induction therapy, and are 60-210 days post-AuSCT. Results: Pts (n=84) have been treated for a median of 16 cycles (2-43). At study entry, 27 (32%) had complete response (CR), 36 (43%) had very good partial remission (VGPR), 20 (24%) had partial remission (PR) and 1 (2%) had minor remission (MR). Best response achieved to date on study is CR in 44 pts (52%), VGPR in 31 pts (37%) and PR in 9 pts (11%). For those who have converted to CR on study, median time to CR was 2 months. Of 22 pts in CR who have been tested for minimal residual disease (MRD) to date, 20 are negative by flow cytometry (minimum of 2 million cells evaluated). Three of 20 have converted from VGPR to MRD negativity while on study. With a median follow up of 23 months, 96% of pts (n=81) remain alive. Ten pts have had PD; of these, 6 had high risk cytogenetics. Two died of PD while receiving salvage therapy. One additional pt died on study in VGPR, after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Four pts withdrew for personal reasons, 4 were removed at physician discretion (prolonged cytopenias [1], drug rash [1], worsening memory impairment [1], therapy related myelodysplastic syndrome (t-MDS) [1]), and 2 lost insurance coverage. Estimated 3 year PFS is 81%. High risk cytogenetics adversely affected PFS (p=0.02). Grade 3-4 Hematologic AEs (no. of pts) were: neutropenia 32% (27), febrile neutropenia 15% (13), thrombocytopenia 8% (7), and anemia 7% (6). Grade 3-4 non-Hematologic AEs (no. of pts): respiratory infections 17% (15), diarrhea 14% (12), fatigue 13% (11), other infections 8% (7), peripheral neuropathy 7% (6), myalgias 6% (5), nausea/vomiting 4% (3), dizziness 2% (2), memory impairment 2% (2), maculopapular rash 2% (2), edema 1% (1). SPMs include intra-epidermal adenocarcinoma of the neck (1), mucinous appendiceal neoplasm (1), t-MDS (1), prostate cancer (1), and melanoma (1). Renal cell carcinoma was diagnosed in 1 pt, 15 months after removal from study for PD. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy during which 33% of 84 pts had improvement in quality of response while on therapy, including 20% who converted to CR. The number of pts experiencing improvement may be underestimated due to ELO interference with paraprotein measurement on electrophoretic studies. Additional follow up is required to determine if the improved quality of responses translate into improvements in PFS and OS. Available data supports conduct of a Phase 3 trial. Disclosures Thomas: Array Pharma: Research Funding; Amgen Inc: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding. Shah:Karyopharm Therapeutics: Employment. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patel:Abbvie: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Poseida Therapeutics, Inc.: Research Funding.

Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) and after myeloablative AuSCT in patients (pts) with multiple myeloma (MM) (Attal et al. NEJM 2012, McCarthy et al. NEJM 2012,). Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAMF7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of pts with MM who have received 1-3 prior therapies. The objective of this phase 2 trial is to evaluate the efficacy and safety of adding ELO to LEN as maintenance therapy post-myeloablative AuSCT. We report preliminary results of the primary (PFS) and secondary (overall survival and toxicity) endpoints. Patients and Methods: Between 4/15/2015-1/27/2016, 28 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2 and q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=27 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until progression. LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity > grade 1 and significant cytopenias (ANC < 1000/mL, platelet count < 100,000/ml). For the 1st 8 weeks, pts The primary endpoint of the study is PFS, defined as the time from AuSCT to clinical progression or death (whichever occurs first), or the time of last contact. Secondary objectives include best response, overall survival, incidence of second primary malignancies and adverse event (AE) profile. Total enrollment of 100 pts is planned. Pts will be followed for 48 months after the last patient is enrolled in the trial. Eligible pts had received no more than 2 lines of induction therapy, and were between 60-210 days post-AuSCT. Results: Patients (n=55) have been treated for a median of 14 cycles (2-30). At study entry, 13 pts (24%) had complete response (CR), 27 (49%) had very good partial remission (VGPR), 14 (25%) had partial remission (PR) and 1 (2%) had minor remission (MR). Best response achieved to date on study is CR in 28 pts (51%), VGPR in 23 pts (42%) and PR in 4 pts (7%). For those who have converted to CR on study, median time to CR has been 5 months. Of 14 pts in CR who have been tested for MRD while on study, 13 are negative by flow cytometry (minimum of 2 million cells evaluated; sensitivity 10 -4-10-5). Two of these 13 have converted from VGPR to MRD negativity at 4 and 14 months on study, respectively. With a median follow up of 21 months, 95% of pts (n=52) remain alive. Three pts (all with high risk disease) had disease progression at 4 (del 17p), 9 (t [4;14]), and 13 (gain 1q) months; of these, 2 have died of progressive disease while receiving salvage therapy. One patient, in VGPR, died on study after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Two pts withdrew for logistical reasons; 2 have been taken off study per physician discretion (prolonged cytopenias (1), drug rash (1)). Grade 3-4 Hematologic AEs (no. of pts) were: neutropenia 35% (16), thrombocytopenia 9% (4), febrile neutropenia 7% (3), and anemia 7% (3). Grade 3-4 non-Hematologic AEs (no. of pts): diarrhea 17% (8), fatigue 17% (8), pneumonia 15% (7), other infections 15% (7), peripheral neuropathy 11% (5), myalgias 9% (4), nausea/vomiting 7% (3), maculopapular rash 4% (2), dizziness 4% (2), edema 2% (1), memory impairment 2% (1). Renal cell carcinoma was diagnosed in 1 patient, 15 months after removal from study for disease progression. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy on which 44% of 55 pts have had improvement in quality of response while on therapy, including 28% who have converted to CR and 24% who have tested MRD negative. The number of pts who have experienced improvement on study may, in fact, be underestimated in this analysis due to elotuzumab interference with measurement on electrophoretic studies. Additional follow up is required to determine if the improved quality of responses translate into improvements in PFS and OS. Disclosures Thomas: Bristol Myers Squibb: Research Funding; Celgene: Research Funding. Shah: Kayopharm: Employment. Lee: Pimera Inc: Consultancy; Eutropics Pharmaceuticals: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Manasanch: merck: Research Funding; adaptive biotechnologies: Consultancy; sanofi: Research Funding; celgene: Consultancy; takeda: Consultancy; quest diagnostics: Research Funding. Patel: Juno: Consultancy; Celgene: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Orlowski: BioTheryX: Consultancy, Membership on an entity's Board of Directors or advisory committees.