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Supplementary Figure from Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study

Supplementary Data from Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study

Purpose:Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton's tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti–PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC.Patients and Methods:Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety and overall response rate (ORR) were co-primary objectives. The secondary objectives were progression-free survival (PFS) and overall survival.Results:Seventy-six patients were evaluated (pembrolizumab, n = 39; pembrolizumab + acalabrutinib, n = 37). Higher frequencies of grade 3–4 treatment-emergent adverse events (AE; 65% vs. 39%) and serious AEs (68% vs. 31%) were observed with combination therapy versus monotherapy. ORR was 18% with monotherapy versus 14% with combination therapy. Median PFS was 2.7 [95% confidence interval (CI), 1.4–6.8] months in the combination arm and 1.7 (95% CI, 1.4–4.0) months in the monotherapy arm. The study was terminated due to lack of clinical benefit with combination treatment. To assess how tumor immune contexture was affected by therapy in patients with pre- and post-treatment biopsies, spatial proteomic analyses were conducted that revealed a trend toward increased CD45+ leukocyte infiltration of tumors from baseline at day 43 with pembrolizumab (monotherapy, n = 5; combination, n = 2), which appeared to be higher in combination-treated patients; however, definitive conclusions could not be drawn due to limited sample size.Conclusions:Despite lack of clinical efficacy, immune subset analyses suggest that there are additive effects of this combination; however, the associated toxicity limits the feasibility of combination treatment with pembrolizumab and acalabrutinib in patients with recurrent or metastatic HNSCC.

Supplementary Figure 2 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Supplementary Figure 4 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Supplementary Methods, Figure Legends 1-6 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Supplementary Figure 6 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Supplementary Figure 3 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Hypoxia inducible factors (HIF) are critical mediators of the cellular response to decreased oxygen tension and are overexpressed in a number of tumors. Although HIF1α and HIF2α share a high degree of sequence homology, recent work has shown that the two α subunits can have contrasting and tissue-specific effects on tumor growth. To directly compare the role of each HIFα subunit in spontaneous tumorigenesis, we bred a mouse model of expanded HIF2α expression and Hif1α+/− mice to homozygotes for the R270H mutation in p53. Here, we report that p53R270H/R270H mice, which have not been previously described, develop a unique tumor spectrum relative to p53R270H/− mice, including a high incidence of thymic lymphomas. Heterozygosity for Hif1α significantly reduced the incidence of thymic lymphomas observed in this model. Moreover, reduced Hif1α levels correlated with decreased stabilization of activated Notch1 and expression of the Notch target genes, Dtx1 and Nrarp. These observations uncover a novel role for HIF1α in Notch pathway activation during T-cell lymphomagenesis. [Cancer Res 2009;69(7):3213–20]

Supplementary Figure 1 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Supplementary Figure 5 from Heterozygosity for Hypoxia Inducible Factor 1α Decreases the Incidence of Thymic Lymphomas in a p53 Mutant Mouse Model

Objectives: As telemedicine has become increasingly utilized during the COVID-19 pandemic, portable otoendoscopy offers a method to perform an ear examination at home. The objective of this pilot study was to assess the quality of otoendoscopic images obtained by non-medical individuals and to determine the effect of a simple training protocol on image quality. Methods: Non-medical participants were recruited and asked to capture images of the tympanic membrane before and after completion of a training module, as well as complete a survey about their experience using the otoendoscope. Images were de-identified, randomized, and evaluated by 6 otolaryngologists who were blinded as to whether training had been performed prior to the image capture. Images were rated using a 5-point Likert scale. Results: Completion of a training module resulted in a significantly higher percentage of tympanic membrane visible on otoendoscopic images, as well as increased physician confidence in identifying middle ear effusion/infection, cholesteatoma, and deferring an in-person otoscopy ( P Conclusions: At-home otoendoscopes can offer a sufficient view of the tympanic membrane in select cases. The use of a simple training tool can significantly improve image quality, though often not enough to replace an in-person otoscopic exam.

Problem definition: We study sourcing behavior in severe conditions where supply disruptions are rare but carry the potential of wiping out several rounds worth of a firm’s profit. Academic/practical relevance: The tradeoff between scale economies from supplier consolidation and risk mitigation from supplier diversification is at the core of firms’ sourcing strategy and one that is empirically understudied. Methodology: We study supplier diversification through a behavioral lens and test theoretically derived predictions under controlled laboratory conditions. Results: Our data provide strong evidence for under-diversification. We posit that this pattern is partly because of the fact that investing in supplier diversification involves an upfront cost to achieve a delayed, and rarely encountered, benefit. Managerial implications: Under-diversification bias is costly, and its causes are difficult to overcome, presenting firms with the daunting task of devising debiasing mechanisms that reinforce a supplier diversification strategy when the rarity of disruptions almost always render supplier consolidation the ex post preferred strategy.

ispartof: HEMASPHERE vol:5 issue:2 ispartof: location:United States status: published

Purpose: Programmed cell death-1 (PD-1) receptor inhibitors have shown efficacy in head and neck squamous cell carcinoma (HNSCC), but treatment failure or secondary resistance occurs in most patients. In preclinical murine carcinoma models, inhibition of Bruton's tyrosine kinase (BTK) induces myeloid cell reprogramming that subsequently bolsters CD8+ T cell responses, resulting in enhanced antitumor activity. This phase 2, multicenter, open-label, randomized study evaluated pembrolizumab (anti–PD-1 monoclonal antibody) plus acalabrutinib (BTK inhibitor) in recurrent or metastatic HNSCC. Patients and Methods: Patients received pembrolizumab 200 mg intravenously every 3 weeks, alone or in combination with acalabrutinib 100 mg orally twice daily. Safety and overall response rate (ORR) were co-primary objectives. The secondary objectives were progression-free survival (PFS) and overall survival. Results: Seventy-six patients were evaluated (pembrolizumab, n = 39; pembrolizumab + acalabrutinib, n = 37). Higher frequencies of grade 3–4 treatment-emergent adverse events (AE; 65% vs. 39%) and serious AEs (68% vs. 31%) were observed with combination therapy versus monotherapy. ORR was 18% with monotherapy versus 14% with combination therapy. Median PFS was 2.7 [95% confidence interval (CI), 1.4–6.8] months in the combination arm and 1.7 (95% CI, 1.4–4.0) months in the monotherapy arm. The study was terminated due to lack of clinical benefit with combination treatment. To assess how tumor immune contexture was affected by therapy in patients with pre- and post-treatment biopsies, spatial proteomic analyses were conducted that revealed a trend toward increased CD45+ leukocyte infiltration of tumors from baseline at day 43 with pembrolizumab (monotherapy, n = 5; combination, n = 2), which appeared to be higher in combination-treated patients; however, definitive conclusions could not be drawn due to limited sample size. Conclusions: Despite lack of clinical efficacy, immune subset analyses suggest that there are additive effects of this combination; however, the associated toxicity limits the feasibility of combination treatment with pembrolizumab and acalabrutinib in patients with recurrent or metastatic HNSCC.

Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.

The non-receptor tyrosine kinase Src activation plays a role in the malignant progression of breast cancer, including development of endocrine therapy resistance and survival of bone metastases. This study investigated whether adding Src kinase inhibitor dasatinib to aromatase inhibitor (AI) therapy improved outcomes in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer (MBC). Postmenopausal patients with ER-positive, HER2-negative MBC (0–1 prior chemotherapies and no prior AI for MBC) were eligible for this non-comparative, parallel group, phase-II study. Patients were randomized to letrozole (2.5 mg/day PO) alone or with dasatinib (100 mg/day PO). Patients with disease progression on letrozole alone could crossover to dasatinib plus continued letrozole. The primary endpoint was clinical-benefit-rate (CBR; complete response + partial response + stable disease ≥6 months). A total of 120 patients were randomized. The CBR of 71% (95% CI 58–83%) was observed with letrozole + dasatinib versus the projected CBR of the combination of 56%. The CBR of 66% (95% CI 52–77%) with letrozole alone also exceeded the projected CBR of 39% with letrozole alone. The CBR was 23% in the crossover arm of letrozole plus dasatinib in patients progressing on letrozole alone. Median progression-free survival with the combination was 20.1 months and 9.9 months with letrozole alone. Letrozole plus dasatinib was well tolerated, although 26% of patients required dasatinib dose reductions. In this non-comparative phase-II trial, the CBR of 71% and the median PFS of 20.1 months with letrozole + dasatinib are encouraging and suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.

Seventeen lesions diagnosed as teat sinus and duct adenomatous hyperplasia were identified in 10 dogs. All of the dogs were small breeds. Six were spayed female and 4 were male, 3 castrated and 1 intact. In 5 cases, the lesions involved multiple teats. They were pink to black, flattened to round, and sometimes crusted. Histologically, the lesions were usually pigmented (16/17), plaque-like to nodular masses composed of polygonal cells arranged in anastomosing trabeculae and bilayered ducts and/or cysts, with a fibrous to mucinous (Alcian blue-positive) stroma and squamous cysts (12/17). Scattered epithelial cells contained single, discrete, clear cytoplasmic vacuoles. Atypia was mild, and the mitotic count per 2.37 mm2 varied from 0 to 15 (average 2.7). Immunohistochemistry was performed on 14 of the lesions from 8 dogs. Epithelial cells were 100% panCK+ and included basally located CK14+/CK5_6+/p63+/calponin− cells and nonbasal CK19+/CK7+ cells. Cells manifesting squamous differentiation were usually panCK+/CK14+/CK5_6+/CK19−/CK7−/p63±/calponin−. In addition to fibroblasts, vimentin positivity was found in disseminated, round to stellate stromal and intraepithelial cells that often had black, granular, cytoplasmic pigment (consistent with dendritic/phagocytic cells and/or melanocytes). Of the 8 dogs for which clinical follow-up information was available, all were still alive and well, with no significant teat changes, development of mammary lesions or other masses 4 to 22 months (median 12.5) after biopsy. The histologic, immunohistochemical, and clinical findings were consistent with teat duct and sinus adenomatous hyperplasia. This is an uncommon, benign proliferative lesion that can involve multiple teats of female and male, small breed dogs.

Objectives: Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma. Material and methods: Patients enrolled in Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and were naïve to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75 × 106 CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE; CRS and ICANS by ASTCT). Results: As of the February 2021 data cutoff (median follow-up: 5.8 months [2.5–9.8]), 20 patients (65% male; median age 60 years [38–75]) received cilta-cel; 1 patient was treated in an outpatient setting. Patients (n = 12

Background: Umbralisib is an oral, once-daily, novel, dual inhibitor of phosphatidylinositol-3-kinase-delta (PI3Kδ) and casein kinase-1ε (CK1ε) that exhibits improved selectivity for the delta isoform of PI3K. Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity that targets a unique epitope on CD20. U2 has been well-tolerated and demonstrated promising activity in heavily pre-treated CLL patients. Herein, results are presented for the randomized, multicenter, Phase 3 UNITY-CLL trial (NCT02612311), which evaluated U2 vs O+Chl in patients with TN and R/R CLL. Methods: Patients ≥18 years of age with treatment-naïve (TN) or relapsed/refractory (R/R) CLL requiring treatment per iwCLL criteria with adequate organ function and ECOG PS ≤2 were eligible. Stratification factors included treatment status (TN vs R/R) and del(17p) status. Patients were initially randomized 1:1:1:1 to receive U2, O+Chl, umbralisib monotherapy, or ublituximab monotherapy. Following establishment of contribution comparing U2 to the single agents, patients were randomized 1:1 to U2 or O+Chl. Umbralisib was given orally at 800 mg once-daily until progression or removal from treatment for other reasons. Ublituximab was administered intravenously at 900 mg on Days 1/2 [split 150/750 mg], 8, and 15 of Cycle 1, Day 1 of Cycles 2 - 6, and on Day 1 every 3 cycles after Cycle 6. O was given intravenously at 1000 mg on Days 1/2 [split 100/900], 8, and 15 of Cycle 1, and Day 1 of Cycles 2 - 6. Chl was given orally at 0.5 mg/kg on Day 1 and 15 of Cycles 1 - 6. Each cycle was 28 days. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS) of U2 vs O+Chl. Key secondary endpoints included IRC-assessed overall response rate (ORR), complete response (CR), undetectable minimal residual disease (uMRD), duration of response (DOR), and safety (assessed from the first dose until 30 days after the last dose of study medication in each arm) as well as contribution of umbralisib and ublituximab to the U2 combination. Results: From Feb 2016 - Oct 2017, 421 pts were randomized to the U2 (n=210) or O+Chl (n=211) arms. The median age was 67 y (range, 36-91); 57% of patients (n=240) were treatment-naïve; 43% (n=181) had R/R CLL (median number of prior treatments = 1); 10% had del(17p), 20% del(11q), and 56% were IgHV unmutated. 66% were male. Demographics were well-balanced between treatment arms. At a median follow-up of 36.2 mos, U2 significantly prolonged PFS vs O+Chl (median 31.9 mos vs 17.9 mos; HR 0.546, 95% CI 0.413-0.720, P The median treatment duration was 23 mos for U2 (range, 0.1 - 49 mos) and 5 mos (range, 0.1 - 7 mos) for O+Chl. G3/4 AEs of interest regardless of causality (U2 vs O+Chl) included neutropenia (30.6% vs 34.7%), thrombocytopenia (3.4% vs 13.1%), diarrhea (12.1% vs 2.5%), infusion related reaction (1.9% vs 3.5%), elevated AST/ALTs (8.3% vs 2%), colitis (3.4% vs 0%) and pneumonitis (2.9% vs 0%). AEs led to treatment discontinuation in 34 patients (16.5%) on U2 and 16 patients (7.6%) on O+Chl. Conclusions: UNITY-CLL is the first randomized Phase 3 study in CLL of a PI3Ki vs. chemoimmunotherapy, and the first randomized study of a PI3Ki in treatment-naive CLL. U2 exhibited a well-tolerated safety profile, and significantly improved PFS vs. standard of care chemoimmunotherapy in patients with treatment-naive and relapsed/refractory CLL. Figure Disclosures Gribben: Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Celgene: Research Funding; Abbvie: Honoraria. Jurczak:Celgene: Research Funding; Afimed: Research Funding; Sandoz-Novartis: Consultancy; European Medicines Agency,: Consultancy; AstraZeneca: Consultancy; Takeda: Research Funding; Janssen China R&D: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Bayer: Research Funding; Acerta: Consultancy, Research Funding; Pharmacyclics: Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; MEI Pharma: Research Funding; Nordic Nanovector: Research Funding; Servier: Research Funding; Merck: Research Funding; Gilead Sciences: Research Funding; Epizyme: Consultancy; Roche: Research Funding; MorphoSys: Research Funding; TG Therapeutics, Inc.: Research Funding; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months. Jacobs:Sanofi Genzyme: Speakers Bureau; Genentech: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Verastem: Consultancy; Seattle Genetics: Consultancy; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; TG Therapeutics, Inc.: Research Funding. Giannopoulos:BMS-Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Honoraria. Wrobel:Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau. Zafar:Bristol Meyers Squibb: Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Florida Cancer Specialists and Research Institute: Current Employment; Sarah Canon Research Institute: Research Funding; Karyopharm: Honoraria; AstraZeneca: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Danilov:Nurix: Consultancy; Celgene: Consultancy; Astra Zeneca: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Gilead Sciences: Research Funding; Verastem Oncology: Consultancy, Research Funding; Pharmacyclics: Consultancy; Abbvie: Consultancy; BeiGene: Consultancy; Takeda Oncology: Research Funding; Karyopharm: Consultancy; TG Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Rigel Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Research Funding; Bayer Oncology: Consultancy, Research Funding. Burke:Gilead: Consultancy; Epizyme: Consultancy; Adaptive: Consultancy; Kura: Consultancy; Astra Zeneca: Consultancy; Bayer: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; Morphosys: Consultancy; Verastem: Consultancy; Roche: Consultancy; Seattle Genetics: Speakers Bureau; Celgene: Consultancy. Goldschmidt:Bristol-Myers Squibb: Speakers Bureau; Amgen: Consultancy; Blue Ridge Cancer Care: Current Employment. Huntington:Genentech: Consultancy; Astrazeneca: Honoraria; TG Therapeutics: Research Funding; Pharmacyclics: Honoraria; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; AbbVie: Consultancy; DTRM: Research Funding. Pinilla Ibarz:AstraZeneca: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Novartis: Consultancy; Sunesis Pharmaceuticals: Consultancy; TG Therapeutics: Consultancy; Sanofi: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Sharman:Bristol Meyers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; BeiGene: Research Funding. Siddiqi:AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Juno: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Oncternal: Research Funding; TG Therapeutics: Research Funding; Janssen: Speakers Bureau; Seattle Genetics: Speakers Bureau. Brander:MEI Pharma: Other, Research Funding; Pfizer: Consultancy, Other; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Tolero: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; NCCN: Other; Verastem: Consultancy, Honoraria, Other, Research Funding; Teva: Consultancy, Honoraria; Novartis: Consultancy, Other; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; NCCN: Other; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding. Kolibaba:TG Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Sumitomo Dainippon Pharma Oncology: Consultancy, Other; Verastem: Honoraria; Genentech: Research Funding; Gilead: Research Funding; Janssen: Research Funding; McKesson Life Sciences: Consultancy; Novartis: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Atara Biotech: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Cell Therapeutics: Research Funding; Compass Oncology: Ended employment in the past 24 months. Ghosh:Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol-Myers Squibb: Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Kite/Gilead: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding. Sportelli:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Miskin:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. O'Connor:Astex Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria, Other: Data Safety Monitoring Committee, Research Funding; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Kymera Therapeutics: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nomocan: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Mundipharma: Other: Consulting; Servier: Consultancy. Weiss:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Flinn:Iksuda Therapeutics: Consultancy; Curis: Research Funding; Infinity Pharmaceuticals: Research Funding; F. Hoffmann-La Roche: Research Funding; Vincera Pharma: Consultancy; Karyopharm Therapeutics: Research Funding; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Triphase Research & Development Corp.: Research Funding; Trillium Therapeutics: Research Funding; TG Therapeutics: Consultancy, Research Funding; Teva: Research Funding; Seattle Genetics: Consultancy, Research Funding; ArQule: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Incyte: Research Funding; Forma Therapeutics: Research Funding; Loxo: Research Funding; BeiGene: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Forty Seven: Research Funding; Genentech, Inc.: Research Funding; Great Point Partners: Consultancy; IGM Biosciences: Research Funding; Juno Therapeutics: Consultancy, Research Funding; Acerta Pharma: Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Research Funding; Johnson & Johnson: Other; Yingli Pharmaceuticals ≠: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Roche: Consultancy, Research Funding; Curio Science: Consultancy; Nurix Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Calithera Biosciences: Research Funding; Merck: Research Funding; Constellation Pharmaceuticals: Research Funding; Agios: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Pfizer: Research Funding; Novartis: Research Funding.

The 7th Heidelberg Myeloma Workshop was held on April 5th and 6th, 2019 at the University Hospital Heidelberg. Main topics of the meeting were (1) diagnostics and prognostic factors, (2) role of immunotherapy in multiple myeloma (MM), (3) current therapy of MM, (4) biology and genomics of MM as well as (5) novel treatment concepts. A debate on the status of minimal residual disease (MRD) driven therapy was held. Diagnostics and treatment of newly diagnosed and relapsed MM are continuously evolving. While advances in the field of (single cell) genetic analysis now allow for characterization of the disease at an unprecedented resolution, immunotherapeutic approaches and MRD testing are at the forefront of the current clinical trial landscape.