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45 citation(s) found for "Vermeulen, T D".

A56-23 Effect of Sex on the Relationship Between Perioperative Risk Factors and Postoperative Pulmonary Complications After Non-Cardiothoracic Surgery in Asa III Patients
Mirza, S, Fernandez-Bustamante, A, Frendl, G, Juraj, S, Subramaniam, B, Martinez-Ruiz, R, Lee, J W, Bartels, K, Giquel, J, Schultz, M, Vermeulen, T D, Leu, C -S, Melo, M F Vidal, Frendl, György , Fernandez-Bustamante, Ana , Subramaniam, Bala , Martinez-Ruiz, Ricardo, Bartels, Karsten , Giquel, Jadelis, Vermeulen, Tom D

Mayo Clinic

American Journal of Respiratory and Critical Care Medicine | May 18, 2026 | Volume: 212 | Issue: Supplement_1 | Pages: No page available

10.1093/ajrccm/aamag162.4640 Get It

Abstract Rationale Postoperative pulmonary complications (PPCs) importantly contribute to postoperative morbidity and mortality, particularly for American Society of Anesthesiologists (ASA) physical status III patients. It remains unclear whether risk factors for PPCs depend on sex. We hypothesised that sex modifies the relationship between perioperative risk factors and PPCs in ASA III patients undergoing noncardiothoracic surgery with general anesthesia. Methods We performed a secondary analysis of prospective data from 1,202 ASA III patients undergoing non-cardiothoracic surgery. Data consisted of preoperative demographics, comorbidities, intraoperative physiology, medications, and procedure information. The primary outcome was a composite of PPCs by postoperative day 7. Mixed-effects linear models incorporated sex as main effect and interaction with covariates. Results Age, chronic obstructive pulmonary disease, upper abdominal surgery, surgical duration, and emergency surgery significantly increased the odds of ≥ 1 PPC by postoperative day 7. Male patients presented a higher rate of ≥ 3 PPCs, and mechanical ventilation was less protective in female patients. Yet, sex did not significantly modify the relationship between perioperative factors and the primary outcome (no p<0.05 for the interaction effect with sex). In the secondary analysis, gastroesophageal reflux disease affected atelectasis more strongly in male than female patients (relative odds-ratios for female versus male =0.27; 95% CI 0.13 to 0.57). Conclusions In ASA III patients undergoing non-cardiothoracic surgery with general anesthesia, perioperative factors are predominantly not significantly modified by sex in their relationship to PPCs. GERD’s association with atelectasis in male patients could be explored in future prospective studies as a target for reducing pulmonary complications. This abstract is funded by: NHLBI - UH3 HL140177
Abstract 5051: A multi-center hospital-based case-control study of lymphoid and myeloid neoplasms (AsiaLymph): Study design and initial findings for education, body mass index, and family history
Lan, Qing, Chan, John K., Lam, Tai Hing , Chen, Kexin, Kwong, Yok Lam, Xu, Caigang , Chiu, Brian CH, Liang, Raymond , Dennis, Ip, Hu, Wei, Bassig, Bryan A. , Purdue, Mark, Xu, Jun, Locke, Sarah J. , Wang, Sophia S., Berndt, Sonja, Hofmann, Jonathan N., Shi, Jianxin , Yu, Kai, Gadalla, Shahinaz, Jones, Rena, Dai, Hongji, Lyu, Zhangyan, Qiu, Lugui , Liu, Wei, zhang, huilai, Wang, Xianhuo, Chanock, Stephen, Linet, Martha, Vermeulen, Roel, Rothman, Nathaniel, Lan, Qing , Hurwitz, Lauren M. , Chan, John K.C., Chen, Kexin , Chiu, Brian C.‐H. , Cerhan, James R. , Hofmann, Jonathan N. , Gadalla, Shahinaz M. , McReynolds, Lisa J. , Jones, Rena R. , Qiu, Lugui , Liu, Wei , Zhang, Huilai , Wang, Xianhuo , Morton, Lindsay M. , Linet, Martha S. , Friesen, Melissa C. , Vermeulen, Roel , Rothman, Nathaniel

Mayo Clinic

Cancer Research | April 3, 2026 | Volume: 86 | Issue: 7_Supplement | Pages: 5051-5051

10.1158/1538-7445.am2026-5051 Get It

Abstract Background: Epidemiologic and other studies have identified environmental, occupational, and genetic risk factors for lymphoid and myeloid malignancies, but most studies have been conducted in Western populations. Investigations in populations with differing exposure patterns, distributions of disease subtypes, and genetic architecture are needed to fully understand hematopoietic tumor etiology. Methods: We conducted a large, multicenter, hospital-based case-control study of lymphoid and myeloid neoplasms in East Asia (AsiaLymph), including 5,671 lymphoid cases, 1,879 myeloid cases, and 3,858 controls. Participants completed a computer-assisted personal interview and provided biospecimens. Cases underwent central pathology review and were coded into the WHO Classification. Herein, we describe the study methods in detail and report association results for education, body mass index, and family history. Results: Greater BMI at age 20 but not at age 40 was associated with odds of total lymphoid neoplasm (per 5 kg/m2 increase: OR [95% CI]: 1.18 [1.09-1.27]), total myeloid neoplasm (OR [95% CI]: 1.17 [1.05-1.29]), and several subtypes. Greater educational attainment was associated with increased odds of total lymphoid neoplasm (for college vs. less than primary education: OR [95% CI]: 1.41 [1.21-1.65]) but not myeloid neoplasm (OR [95% CI]: 1.17 [0.95-1.45]; p-heterogeneity=0.02). There were also positive associations between family history of hematologic cancer in first degree relatives and odds of lymphoid neoplasm (OR [95% CI]: 1.53 [1.15-2.03]) and myeloid neoplasm (OR [95% CI]: 1.65 [1.11-2.44]) and specific subtypes. None of the evaluated risk factors were associated with NK/T-cell lymphoma, which supports a distinct etiology for this subtype. Conclusion: The AsiaLymph Study is one of the largest molecular epidemiology studies of both lymphoid and myeloid neoplasms with standardized World Health Organization classification of histopathologic subtypes and will serve as a valuable resource for etiologic investigations into risk factors for these malignancies. Citation Format: Qing Lan, Lauren M. Hurwitz, John K. Chan, Tai Hing Lam, Kexin Chen, Yok Lam Kwong, Xu Caigang, Brian CH Chiu, Raymond Liang, Ip Dennis, Wei Hu, Bryan Bassig, Mark Purdue, Jun Xu, Sarah Locke, Sophia S. Wang, James R. Cerhan, Sonja Berndt, Jonathan N. Hofmann, Jianxin Shi, Kai Yu, Shahinaz Gadalla, Lisa J. McReynolds, Rena Jones, Hongji Dai, Zhangyan Lyu, Lugui Qiu, Wei Liu, Huilai Zhang, Xianhuo Wang, Lindsay M. Morton, Stephen Chanock, Martha Linet, Melissa C. Friesen, Roel Vermeulen, Nathaniel Rothman. A multi-center hospital-based case-control study of lymphoid and myeloid neoplasms (AsiaLymph): Study design and initial findings for education, body mass index, and family history [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5051.
Circulating levels of insulin‐like growth factor I ( IGF ‐I) and risk of multiple myeloma: An observational and Mendelian randomisation study
Benavente, Yolanda, Hermosa, Sara, Clay‐Gilmour, Alyssa, Brown, Elizabeth , Hofmann, Jonathan N., Rothman, Nathaniel, Lan, Qing, Berndt, Sonja I., Albanes, Demetrius, Purdue, Mark, Chanock, Stephen J., Norman, Aaron, Kumar, Shaji K., Vachon, C M, Novak, Anne J. , Ghesquieres, Herve, Bracci, Paige M., Holly, Elizabeth, Griffin, Rosalie G., Vermeulen, Roel , Hjalgrim, Henrik, Smedby, Karin Ekström, Cheah, Simon , Monnereau, Alain, Arslan, Alan, Zhang, Yawei, Camp, Nicola J., Sborov, Douglas W., Ziv, Elad , Joseph, Vijai, Teras, Lauren R., Patel, Alpa V. , Vajdic, Claire M., Cocco, Pierluigi, Alemany, Laia, McKay, James, Casabonne, Delphine , Monnereau, Alain , Brown, Elizabeth E , Machiela, Mitchell J , Slager, Susan L , Cerhan, James R , Rajkumar, S Vincent , Novak, Anne J , Habermann, Thomas , Salles, Gilles A , Hildebrandt, Michelle A T , Jayasekara, Harindra , Cheah, Simon , Kane, Eleanor , Guilloteau, Adrien , Casabonne, Delphine , Ziv, Elad , Benavente, Yolanda , Papadimitriou, Nikos , Clay‐Gilmour, Alyssa , Hofmann, Jonathan N. , Rothman, Nathaniel , Lan, Qing , Berndt, Sonja I. , Albanes, Demetrius , Machiela, Mitchell J. , Chanock, Stephen Jacob , Bhatti, Parveen , Cozen, Wendy , Slager, Susan L. , Cerhan, James R. , Rajkumar, S. Vincent , Habermann, Thomas M. , Link, Brian K. , Salles, Gilles , Ghesquières, Hervé , Bracci, Paige M. , Waller, Rosalie G. , Hildebrandt, Michelle A.T. , Kolijn, Pieter Martijn , Hjalgrim, Henrik , Jayasekara, Harindra , Chen, Yu , Camp, Nicola J. , Sborov, Douglas W. , Osman, Afaf E.G. , Vivo, Immaculata De , Teras, Lauren R. , Kane, Eleanor , Vajdic, Claire M. , Alemany, Laia, Sáinz, Juan , McKay, James, Birmann, Brenda M.

Mayo Clinic

British Journal of Haematology | March 24, 2026 | Volume: 208 | Issue: 6 | Pages: 1942-1953

10.1111/bjh.70444 | PMID 41873017 Get It

Summary Evidence for an association between insulin‐like growth factors (IGF) and multiple myeloma (MM) is inconsistent. We examined total IGF‐I concentrations and risk of MM by combining baseline serological data among UK Biobank participants ( n = 444 187; 732 incident MM) with a two‐sample Mendelian randomisation (MR) analysis using identified genetic variants associated with circulating total IGF‐I and IGF‐binding protein 3 (IGFBP‐3) in the InterLymph consortium (2434 MM and their 2567 controls). Finally, additional lymphoid neoplasm (LN) subtypes were included for comparison with the main hypothesis. Circulating IGF‐I level was positively associated with MM risk Hazard ratio‐HR‐per one standard deviation‐SD‐increase (HR 1‐SD = 1.11, 95% confidence interval [CI]: 1.01–1.22; p ‐value = 0.03), especially closer to diagnosis. Genetically inferred IGF‐I levels were associated with increased MM risk (odds ratio [OR] = 1.27, 95% CI: 1.05–1.54) but not with any other LNs. Genetically inferred IGFBP‐3 levels showed no associations with any LN evaluated. Corroborating previous findings, in a secondary analysis, IGF‐I levels were associated with the risk of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in males with higher body mass index (HR 1‐SD in obese male = 1.36, 95% CI: 1.14–1.61). Our serological and MR analyses suggest a contributing role of IGF‐I in the susceptibility of MM; the CLL/SLL findings warrant further investigation considering sex‐specific adiposity.
Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers
Blechter, Batel , Wang, Xiaoyu , Karsonaki, Christiana, Shi, Jianxin , Shiraishi, Kouya , Choi, Jiyeon , Matsuo, Keitaro , Chen, Tzu‐Yu , Kim, Young Tae , Choudhury, Parichoy Pal , Williams, Jacob , Landi, Maria Teresa , Yin, Zhihua , Zhou, Baosen , Seow, Wei Jie , Song, Lei , Chang, I‐Shou , Chien, Li-Hsin , Wong, Maria Pik , Richardson, Brian Douglas , Li, Shilan , Breeze, Charles E. , Bassig, Bryan A. , Sm, Jason Yy Wong, Chung, Lap Ping, Zhang, Xu‐Chao , Caporaso, Neil E. , Chang, Jiang , Ho, Jcm , Momozawa, Yukihide , Kobayashi, Masashi , Okubo, Kenichi , Honda, Takayuki , Kunitoh, Hideo , Watanabe, Shun-ichi, Hamamoto, Ryuji , Goto, Kōichi , Minamiya, Yoshihiro, Wakai, Kenji , Murakami, Yoshinori , Shimizu, Kimihiro , Suzuki, Hiroyuki , Ohtaki, Yoichi , Tanaka, Kazumi , Wu, Tangchun , Wei, Fusheng, Kim, Yeul Hong , Chang, Gee-Chen , Chen, Kuan‐Yu, Chen, Yuh-Min, Park, Jae Yong , Kweon, Sun-Seog, Gao, Yu‐Tang , Schwartz, Ann G. , Gorlov, Ivan , Wu, Xifeng , Yang, Ping , Lam, Stephen , Bojesen, Stig E. , Ji, Bu‐Tian , Wichmann, H. E., Christiani, D.C., Brennan, Paul , McKay, James , Field, John K. , Shete, Sanjay , Marchand, Loı̈c Le, Liu, Geoffrey , Andrew, Angeline S. , Zienolddiny-Narui, Shan, Grankvist, Kjell , Taylor, Fiona, Aldrich, Melinda C. , Jeon, Hyo‐Sung, Hu, Zhibin , Burdett, Laura, Yeager, Meredith, Hutchinson, Amy , Hicks, Belynda , Liu, Jia , Berndt, Sonja I, Wu, Wei , Wang, Junwen , Choi, Jin Eun , Park, Kyong Hwa , Sung, Sook Whan , Tan, Wen , Sihoe, Alan , Choi, Yi Young, Hung, Hsiao-Han , Vermeulen, Roel , Wu, Junjie , Tsai, Fang-Yu , Chan, John K. C., Li, Jihua , Lin, Hsien-Chih, Liu, Jie , Sawada, Norie , Yamaji, Taiki , Wyatt, Kathleen , Qi, T. Y., Li, Xuelian , Ren, Yangwu , Chao, Ann, Zhu, Junjie , Chen, Chih‐Yi , ScD, Chien-Jen Chen, Stevens, Victoria L. , Fraumeni, Joseph F., Lin, Kuang , Walters, Robin G., Chen, Zhengming, Chatterjee, Nilanjan , Gorlova, Olga Y. , Hsiung, Chao A. , Chanock, Stephen J, Rothman, Nathaniel , Kohno, Takashi , Lan, Qing, Kartsonaki, Christiana , Liu, Geoffrey , Field, John K , Matsuo, Keitaro , Wang, Junwen , Bojesen, Stig E , Grankvist, Kjell , Chen, Chih-Yi , Dai, Juncheng , Hung, Rayjean J. , Chen, Kexin , Shu, Xiao-Ou , Choudhury, Parichoy Pal , Lin, Dongxin , Zheng, Wei , Wang, Jiucun , Hu, Wei , Cai, Qiuyin , Hong, Yun‐Chul , Kim, Hee Nam , Wu, Yi-Long Lung Cancer , Richardson, Brian Douglas , Zhang, Tongwu , Wang, Zhaoming , Kim, Jin Hee , Albanes, Demetrius , Shin, Min‐Ho , Chung, Lap-Ping, Yang, Yang , Zheng, Hong , Dai, Hong , Yatabe, Yasushi , Kim, Young‐Chul , Daigo, Yataro , Kamatani, Yoichiro , Kobayashi, Masashi , Hosgood, Howard Dean , WATANABE, Shun-ichi J. , Miyagi, Yohei , Matsumoto, Shingo , Horinouchi, Hidehito , Tsuboi, Masahiro , Takahashi, Atsushi , Goto, Akiteru , Hara, Megumi , Nishida, Yuichiro , Takeuchi, Kenji , Matsuda, Koichi , Murakami, Yoshinori, Suzuki, Hiroyuki , Saito, Motonobu , Machiela, Mitchell J. , Oh, In‐Jae , Lee, Victor , Su, Wu‐Chou , Seow, Adeline , Kweon, Sun-Seog , Liu, Jianjun , Houlston, Richard S. , Tardón, Adonina , Chen, Chu, Johansson, Mattias , Risch, Angela , Bickeböller, Heike , Rennert, Gad , Arnold, Susanne M. , Davies, Michael P.A. , Kiemeney, Lambertus A. , Cox, Angela , Yuan, Jian-Min , Lazarus, Philip J. , Schabath, Matthew B. , Jiang, Shih Sheng , Chen, Chung–Hsing , Hsiao, Chin‐Fu , Yeager, Meredith , Liu, Jia , Berndt, Sonja I. , Li, Yuqing , Kang, Chang Hyun , Wang, Wen‐Chang , Xu, Jun, Guan, Peng , Yu, Chong‐Jen , Yang, Gong , Park, In Kyu , Cheng, Iona C. , Song, Bao, Wyatt, Kathleen , Ma, Hongxia , Zhu, Meng , Wang, Yifan , Qi, Tianchen, Iwasaki, Motoki , Wu, Guoping , Yang, Pan‐Chyr , Walters, Robin G. , Chatterjee, Nilanjan , Amos, Christopher I. , Shen, Hongbing , Rothman, Nathaniel , Lan, Qing , Zhang, Haoyu

Mayo Clinic

JNCI: Journal of the National Cancer Institute | September 18, 2025 | Volume: 118 | Issue: 2 | Pages: 231-249

10.1093/jnci/djaf272 | PMID 41032288 Get It

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.
Genetically determined body mass index is associated with diffuse large B‐cell lymphoma in polygenic and Mendelian randomization analyses
Moore, Amy , Teras, Lauren R. , Machiela, Mitchell J. , Arias, Joshua , Monnereau, Alain , Wang, Zhaoming , Vermeulen, Roel , Smedby, Karin E. , Spinelli, John J., Nieters, Alexandra , Bracci, Paige M. , Camp, Nicola J. , Hjalgrim, Henrik, Adami, Hans‐Olov , Albanes, Demetrius, Becker, Nikolaus, Benavente, Yolanda , Clavel, Jacqueline , Curtin, Karen , Ghesquières, Hervé, Glimelius, Bengt, Lan, Qing , Liebow, Mark , McKay, James , Offit, Kenneth, Padoan, Marina, Patel, Alpa V. , Ríboli, Elio , Severson, Richard K., Tinker, Lesley F. , Weinstein, Stephanie J. , Zheng, Tongzhang, Chanock, Stephen J., Rothman, Nathaniel , Berndt, Sonja I. , Teras, Lauren R , Wang, Zhaoming , Vajdic, Claire M , De Vivo, Immaculata , Boffetta, Paolo , Brooks-Wilson, Angela R , Canzian, Federico , Southey, Melissa C , Cerhan, James R , Berndt, Sonja I , Clavel, Jacqueline , Machiela, Mitchell J , Riboli, Elio , Kane, Eleanor , Panagiotou, Orestis A. , Doo, Nicole Wong , Slager, Susan L. , Vajdic, Claire M. , Vijai, Joseph , Giles, Graham G. , Link, Brian K. , Arslan, Alan A. , Salles, Gilles , Cozen, Wendy , Vivo, Immaculata De , Albanes, Demetrius , Bisanzi, Simonetta , Brennan, Paul E. , Brooks‐Wilson, Angela , Canzian, Federico , Conde, Lucía , Cox, David G. , Foretová, Lenka , Glimelius, Bengt , Habermann, Thomas M. , Hofmann, Jonathan N. , Lan, Qing , Lincoln, Anne , Maynadié, Marc , Melbye, Mads , Miligi, Lucia , Milne, Roger L. , Molina, Thierry Jo , Morton, Lindsay M. , North, Kari E. , Offit, Kenneth, Piro, Sara , Purdue, Mark P. , Ravichandran, Vignesh , Southey, Melissa C. , Staines, Anthony , Travis, Ruth C. , Wang, Sophia , Weiderpass, Elisabete , Rothman, Nathaniel , Birmann, Brenda M. , Cerhan, James R.

Mayo Clinic

International Journal of Cancer | September 5, 2025 | Volume: 158 | Issue: 1 | Pages: 45-59

10.1002/ijc.70039 | PMID 40910475 Get It

Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.
Evidence-based guideline: premature ovarian insufficiency,
Panay, Nick , Anderson, Richard A. , Bennie, Amy , Cedars, Marcelle I. , Davies, Melanie , Ee, Carolyn , Gravholt, Claus Højbjerg , Kim, Kimberly Q, Rocca, Walter A. , POI, ESHRE, ASRM, CREWHIRL, and IMS Guideline Group on, Yeganeh, Ladan , Giri, Rinky, Flanagan, M. , Mousa, Aya , Nappi, Rossella E , Rocca, Walter A , Teede, Helena , Vermeulen, Nathalie , Vincent, Amanda J , Gravholt, Claus H , Kalantaridou, Sophia , Kallen, Amanda Nicole , Misrahi, Micheline , Ruan, Xiangyan , Vogt, Elinor , POI, ESHRE, ASRM, CREWHIRL, and IMS Guideline Group on, Flanagan, Madeline

Mayo Clinic

Human Reproduction Open | November 12, 2024 | Volume: 2024 | Issue: 4 | Pages: No page available

10.1093/hropen/hoae065 | PMID 39660328 Get It

Abstract STUDY QUESTION How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature? SUMMARY ANSWER The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI. WHAT IS KNOWN ALREADY Premature ovarian insufficiency (POI) presents a significant challenge to women’s health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessments were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials (RCTs) on POI included in the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH >25 IU is required for diagnosis of POI, and guidance that AMH testing, repeat FSH measurement, and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care. LIMITATIONS, REASONS FOR CAUTION The guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides health care professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women's Health in Reproduction Life (CRE-WHiRL), and International Menopause Society (IMS), covering expenses associated with the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive payments. N.P. declared grants from Bayer Pharma (research and consultancy) and NIHR—research POISE; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex, Viatris; honoraria from Astellas, Bayer, Besins, Gedeon Richter, Theramex, Viatris; support for attending meetings and/or travel from Astellas, Bayer, Theramex, Viatris; President, International Menopause Society, Medical Advisory Committee member, British Menopause Society, Patron Daisy Network. A.J.V. declared grants from Amgen Australia, Australian NHMRC, and Australian MRFF; consulting fees from IQ Fertility; honoraria from the Australasian Menopause Society; participation on a Data Safety Monitoring Board or Advisory Board of Astellas; Board Member of the International Menopause Society (2020 to current) and Past president of the Australasian Menopause Society (2017–2019); R.A.A. declared grants from Roche (Research support, to institution), and participation on a Data Safety Monitoring Board of Bayer. M.C. declared grants from NHI; payments or honoraria from Up-to-Date (as editor/reviewer); Board Member of American Society of Reproductive Medicine, and of American Gynecological and Obstetrical Society. M.D. declared (NIHR—HTA Reference Number: NIHR133461; NIHR—HTA Reference Number: NIHR128757; Action Medical Research and Borne: GN2818) consulting fees from a small personal medical practice, support for attending meetings and/or travel from ESHRE, Bayer and UCLH special Trustees; Participation on the Advisory Board of the British Menopause Society, UKSTORE project, the Progress Educational Trust, and the Turner Syndrome Support Society UK; Leadership or fiduciary roles in the British Fertility Society (Trustee), Elizabeth Garrett Anderson Hospital Charity (chair of Trustees), and the Essex Wynter charitable trust (Trustee). C.E. declared being Chair of a SIG from the Royal Australian College of General Practitioners Integrative Medicine Specific Interest Group and Program Lead for Next Practice Western Sydney Integrative Health. C.H.G. declared grants from Novo Nordisk Foundation (Nos. NNF15OC0016474 and NNF20OC0060610), sygesikringen danmark (No 2022-0189), and the Independent Research Fund Denmark (Nos. 0134-00406 and 0134-00130B); consulting fees from Novo Nordisk, Merck, and Astra Zeneca. S.K. declared grants from Roche diagnostics. A.K. declared grants from NIH R01 5R01HD101475; consulting fees as Medical Reviewer for Flo and for Healthline; honoraria as Medical Consultant for Summus; support for attending meetings from the Reproductive Scientist Development Program; Society for Reproductive Investigation Council Member and Society for Assisted Reproduction Registry/Validation Chair; R.E.N. declared consulting fees from Astellas, Bayer Pharma, Besins Healthcare, Fidia, Theramex; honoraria from Abbott, Astellas, Exeltis, Fidia, Gedeon Richter, Merck & Co, Novo Nordisk, Shionogi Limited, Theramex, Viatris; payment for expert testimony from Vichy Laboratories; Participation in Data Safety Monitoring Board of Advisory board from Astellas and Bayer Healthcare; President elect of the International Menopause Society (IMS). H.T. declared a grant from NHMRC Centre for Research Excellence for women’s health in reproductive life. A.B. declared being chair of the Daisy Network Charity. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, ASRM, CRE-WHiRL, and IMS, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. The collaborating societies make no warranty, expressed or implied, regarding the clinical practice guidelines and specifically exclude any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.)
O-111 Premature ovarian insufficiency: new data and updated guidance
Panay, Nicholas , Bennie, A, Cedars, Marcelle I. , Davies, Melanie , Kim, K., Rocca, Walter A. , Anderson, Richard A. , Bennie, Amy , Ee, Carolyn , Gravholt, Claus Højbjerg , Kalantaridou, Sophia , Kallen, Amanda Nicole , Misrahi, Micheline , Nappi, Rossella E , Ruan, Xiangyan , Teede, Helena , Vermeulen, Nathalie , Vogt, Elinor , Vincent, Amanda J

Mayo Clinic

Human Reproduction | July 3, 2024 | Volume: 39 | Issue: Supplement_1 | Pages: No page available

10.1093/humrep/deae108.122 Get It

Abstract Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with significant implications both physically and emotionally. Despite its life-altering impact, there remain substantial unknowns in the causes this condition and how to optimally manage its various sequelae While such unknows provide direction for future research, they also underscore the need for clinical guidance. In 2015, under the auspices of ESHRE, a group of experts evaluated the existing best evidence and published the first European guideline on the management of premature ovarian insufficiency. The update of this Guideline was performed in an international collaboration of experts representing American Society for Reproductive Medicine (ASRM), International Menopause Society (IMS), and the Centre for Research Excellence in Women’s Health in Reproductive Life (CRE WHiRL). The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including musculoskeletal health, cardiovascular health, neurological health, sexual function and general well being, and treatment options, including hormone therapy. The list of clinical questions was expanded from the questions included in the guideline from 2015. Based on a scoping survey and appreciation of emerging knowledge of POI, questions were added on the role of AMH in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for hormone treatment in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. The draft guideline published for stakeholder review includes a total of 142 recommendations. One third of these recommendations were formulated as good practice points. Of the evidence-based recommendations, almost 80% were formulated as strong recommendations, even if the evidence base for most evidence-based recommendations was limited to observational data (level very low or low), supporting a call for future research. The guideline group hope that the new POI Guideline will improve the clinical management of this devastating condition.
Plain Language Summary of the MAIA Study of Daratumumab Plus Lenalidomide and Dexamethasone for the Treatment of People with Newly Diagnosed Multiple Myeloma
Kumar, Shaji , Plesner, Torben , Orlowski, Robert Z. , Hulin, Cyrille , Goldschmidt, Hartmut , Macro, Margaret , Leleu, Xavier , Wang, Jianping , Rampelbergh, Rian Van , Uhlar, Clarissa, Vermeulen, Jessica, Duran, Joana , Borgsten, Fredrik, Usmani, Saad Z. , Orlowski, Robert Z. , Usmani, Saad , Facon, Thierry T.F. , Moreau, Philippe , Bahlis, Nizar Jacques , Basu, Supratik , Nahi, Hareth , Quach, Hang , Perrot, Aurore , Weisel, Katja C , Raje, Noopur , Frenzel, Laurent

Mayo Clinic

Future Oncology | May 22, 2023 | Volume: 19 | Issue: 13 | Pages: 887-895

10.2217/fon-2023-0082 | PMID 37212642 Get It

Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone: Update of the Phase 3 MAIA Tria
Kumar, Shaji , Plesner, Torben , Hulin, Cyrille , Goldschmidt, Hartmut , Venner, Chris , Mace, Joseph R., Tiab, Mourad, Macro, M. , Leleu, Xavier , Fastenau, John , Gries, Katharine S. , Ho, Kai Fai, Mistry, Pankaj , Tromp, Brenda, Delioukina, Maria , Vermeulen, Jessica, Perrot, Aurore , Facon, Thierry T.F. , Orlowski, Robert Z. , Moreau, Philippe , Bahlis, Nizar Jacques , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Weisel, Katja C , Raje, Noopur , Frenzel, Laurent , Liu, Kevin , Usmani, Saad Z.

Mayo Clinic

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 1655-1655

10.1182/blood-2021-144421 Get It

Abstract Introduction: Multiple myeloma (MM) is a chronic hematologic malignancy with a high symptom burden that can have a substantial negative impact on patients' (pts) health-related quality of life (HRQoL). The introduction of novel triplet regimens for newly diagnosed MM (NDMM) has extended progression-free survival (PFS) and overall survival (OS); however, adverse events and demanding administration and monitoring schedules have a further negative effect on HRQoL, especially among pts who are transplant ineligible (TIE) due to older age and/or frailty. Optimizing initial treatment is particularly important in older pts, many of whom receive only 1 line of therapy. The phase 3 MAIA trial compared daratumumab, lenalidomide, and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd) in TIE pts with NDMM. At a median follow-up of 28 months, D-Rd significantly prolonged PFS and was associated with faster and sustained clinically meaningful improvements in patient-reported outcomes (PROs) vs Rd. Results of an updated analysis with longer follow-up recently confirmed a significant benefit in OS with D-Rd vs Rd as well as a continued significant PFS benefit and higher rates of complete response or better and very good partial response or better. Here we present an update of the HRQoL analysis with additional follow-up. Methods: MAIA (NCT02252172) is a randomized, open-label, active controlled, multicenter, phase 3 study of TIE pts with NDMM who were randomly assigned 1:1 to receive D-Rd or Rd until disease progression (PD) or unacceptable toxicity. PROs were recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EQ-5D-5L visual analog scale. EORTC QLQ-C30 has 30 items comprising 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaires were completed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, and every 6 months thereafter until PD. Analyses were conducted on all pts with a baseline and ≥1 post-baseline PRO assessment. Pts were censored at PD or discontinuation of study treatment. Thresholds for meaningful improvement and worsening were defined a priori based on published literature (≥10-point change). Treatment effect was analyzed using a mixed-effects model for repeated measurements including baseline value, visit, treatment, visit by treatment interaction, and randomization stratification factors as fixed effects and individual subject as random effect. Results: At a median follow-up of 56.2 months, discontinuation rates were lower with D-Rd than Rd (56.8% vs 80.8%). For GHS, physical functioning, fatigue, pain, and dyspnea, PROs that are particularly relevant to pts with MM, a numerically greater proportion of pts achieved a meaningful improvement with D-Rd vs Rd (Table 1). Differences were significant for physical functioning, fatigue, and dyspnea. The proportion of pts achieving a meaningful worsening on therapy was similar in both treatment groups (Table 1). The median time to improvement was numerically shorter with D-Rd vs Rd for physical functioning and pain and with Rd vs D-Rd for GHS and fatigue; differences were not significant (Table 2). The median time to worsening of fatigue was similar between groups, numerically longer for D-Rd vs Rd for GHS, and significantly longer with D-Rd than Rd for physical functioning, pain, and dyspnea (Table 2). Median time to worsening of pain with D-Rd vs Rd was 39.43 vs 17.97 months, reflective of an additional ~21 months without worsening pain among pts treated with D-Rd. Between-group differences for least squares mean change from baseline for these 5 PROs favored D-Rd vs Rd at all assessment time points except cycle 3 for physical functioning and cycle 6 for fatigue; differences were significant at ≥1 timepoint for each scale. Conclusions: These updated PRO analyses from the MAIA study demonstrate sustained and clinically meaningful improvements in HRQoL with D-Rd vs Rd with almost 5 years of follow-up. These results are consistent with the clinical benefits of superior PFS, OS, and deep responses observed with D-Rd compared with Rd and support the use of D-Rd in older pts. Figure 1 Figure 1. Disclosures Perrot: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar: Roche-Genentech: Consultancy, Research Funding; Novartis: Research Funding; Celgene: 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; Sanofi: Research Funding; Bluebird Bio: Consultancy; Tenebio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Plesner: Takeda: Research Funding; Oncopeptides: Other: Advisor, Research Funding; Genentech: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; AbbVie: Other: Advisor, Research Funding; Celgene: Other: Advisor, Research Funding; Janssen: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Oncopeptides: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene BMS: Honoraria; Amgen: Honoraria; Abbvie: Honoraria. Bahlis: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: Takeda: Honoraria; Sanofi: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; abbvie: Honoraria. Quach: CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Goldschmidt: Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. O'Dwyer: ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Bristol Myers Squibb: Research Funding. Venner: BMS: Honoraria; Amgen: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Weisel: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria, Other: Travel accomodation, Research Funding; Janssen: Honoraria, Other: Travel accomodation, Research Funding; Celgen/BMS: Honoraria. Leleu: Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau: Janssen: Current Employment, Current equity holder in publicly-traded company. Gries: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Ho: DRG Abacus: Consultancy; Janssen: Consultancy; Emalex Biosciences: Consultancy. Mistry: Janssen: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Usmani: Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau.