Abdallah, Al-Ola

Goodman, Aaron

McClune, Brian

Mohyuddin, Ghulam Rehman

Prasad, Vinay

eScholarship - University of California

UCSFUC San Francisco Previously Published WorksTitleMultiple myeloma triplet therapies: baseline characteristics and control groupsPermalinkhttps://escholarship.org/uc/item/8q14t32gJournalThe Lancet, 397(10285)ISSN0140-6736AuthorsMohyuddin, Ghulam RehmanAbdallah, Al-OlaMcClune, Brianet al.Publication Date2021-05-01DOI10.1016/s0140-6736(21)00274-9Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, availalbe at https://creativecommons.org/licenses/by/4.0/ Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaCorrespondence1620 www.thelancet.com   Vol 397   May 1, 2021women’s, children’s, and adolescents’ health—totalling US$20 billion—will be amplified by the PMNCH as part of this call.I urge the global health community to support Patel and Phillips’ call for a moral imagination that makes us think about how we frame solutions to old and new problems. We are morally obliged to heed that call.I declare no competing interests.© 2021 World Health Organization. Published by Elsevier Ltd. All rights reserved.Helga Fogstadfogstadh@who.intPartnership for Maternal, Newborn and Child Health, World Health Organization, CH 1211 Geneva, Switzerland1 Patel MS, Phillips CB. COVID-19 and the moral imagination. Lancet 2021; 397: 648–50.2 Roberton T, Carter ED, Chou VB, et al. Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study. Lancet Glob Health 2020; 8: e901–08.1 Bozorgmehr K. Power of and power over COVID-19 response guidelines. Lancet 2020; 396: e67.2 Stoeklé HC, Hervé C. COVID-19: act first, think later. Am J Bioeth 2020; 20: W1.3 Massé R. Anthropology of morals and ethics. Presses de l’Université de Laval 2015; 221: 340 (in French).4 Stoeckle HC, Hervé C. COVID-19: what’s next for bioethics? Can J Bioeth 2020; 3: 93–94 (in French).will happen after the COVID-19 pandemic, which is far from over, to prepare for any possible pandemics in the future.4Health-care providers and research institutions worldwide should engage in a veritable reflection of practical ethics to adapt their guidelines to the clinical and scientific reality during this time and to improve the experience of doctors and scientists. Over the past few months, these specialists have been confronted with an entirely new situation that merits the development of an ethical vision of actions. The legitimate needs and fears of populations also need to be factored in, without forgetting the constraints inherent in an increasingly globalised world.This reflection should lead to the embodiment of practical ethics that can mediate tensions between health and economics, and between individuals and the community, by distinguishing cultural and temporal aspects. Indeed, identifying identical solutions for all countries and transforming hetero-geneous health systems is difficult. A practical, pragmatic, and rational ethical reflection is therefore needed to include these different elements.At the start of the COVID-19 pan-demic, it was time to act and apply guidelines.2 Almost a year later, the goal is to define an ethical vision capable of bringing countries together, while considering their specific char-acteristics. Now is the time to call into question the subsidiarity of health at a worldwide level to arrive at useful functional coexistences between systems on the basis of different standards and cultural values.We declare no competing interests.Henri-Corto Stoeklé, Achille Ivasilevitch, *Christian Hervéchristian.herve@parisdescartes.frDepartment of Ethics and Scientific Integrity, Foch Hospital, Suresnes, France (H-CS, AI, CH); Laboratory of Business Law and New Technologies, Paris-Saclay University, Montigny-Le-Bretonneux, France (AI); International Academy of Medical Ethics and Public Health, University of Paris, 75006 Paris, France (CH); Veterinary Academy of France, Paris, France (CH)Women, children, and adolescents in the post-pandemic worldMahomed Patel and Christine Phillips1 offer compelling arguments for a post-COVID-19 world that breaks with business as usual. I wholeheartedly agree. An early study2 of the indirect impact of COVID-19 on maternal and child mortality estimated 2 million additional deaths in 2020–21 compared with pre-pandemic figures because of the disruptions to essential health services.The world after the pandemic offers a unique opportunity for radical change by placing women, children, and ado-lescents at the heart of investments in health and opportunities for socio-economic repair and resilience.New solutions can be discovered to advance health—eg, by challenging the dominance of biomedical and technical frameworks that detract from the effect of power relations on health outcomes. We also need a global investment framework that includes women, children, and adolescents at its core, and features components on preparedness and response.To ensure that the experiences of women and young people drive policy and research in this area, the Partnership for Maternal, Newborn and Child Health (PMNCH) issued a seven-point call to action in 2020, to direct investment and policy towards the unequal social, economic, and political factors driving the impact of COVID-19 and its future consequences. Commitments by ten countries to Published Online April 19, 2021 https://doi.org/10.1016/ S0140-6736(21)00792-3For more on the PMNCH see https://www.who.int/pmnch/en/For the PMNCH call to action see https://www.who.int/pmnch/media/news/2020/call-to-action-on-COVID-19/en/Multiple myeloma triplet therapies: baseline characteristics and control groupsGiven that the bortezomib and dexa-methasone combination treatment has been shown to be inferior to contemporary treatments in clinical trials well before the BOSTON trial began enrolling,1 why did Sebastian Grosicki and colleagues2 consider bortezomib and dexamethasone for the control group for patients in the USA? How many patients from the USA were enrolled?The investigators claim that the BOSTON trial2 included patients with cardiac and other major organ dysfunctions. What percentage of the patients enrolled in this study actually had cardiac or major organ dysfunction? Given that triplet therapy being administered at diagnosis is standard in the USA, what percentage of patients at first relapse had previously received a triplet Correspondencewww.thelancet.com   Vol 397   May 1, 2021 1621plasmacytomas treated with selinexor, bortezomib, and dexamethasone?TT reports personal fees from Medical Network Systems and Bionics. MS declares no competing interests.*Motoharu Shibusawa, Tetsuya Tanimotom_sibusawa@hotmail.comIMS group Shinmatsudo Central General Hospital, Department of Hematology, Chiba 270–0034, Japan (MS); Navitas Clinic Kawasaki, Kanagawa, Japan (TT)1 Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet 2020; 396: 1563–73.2 Wu P, Davies FE, Boyd K, et al. The impact of extramedullary disease at presentation on the outcome of myeloma. Leuk Lymphoma 2009; 50: 230–35.3 Avivi I, Cohen YC, Suska A, et al. Hematogenous extramedullary relapse in multiple myeloma - a multicenter retrospective study in 127 patients. Am J Hematol 2019; 94: 1132–40.4 Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C, Lazzarino M. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol 2010; 21: 325–30.5 Caers J, Paiva B, Zamagni E, et al. Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel. J Hematol Oncol 2018; 11: 10.2 Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet 2020; 396: 1563–73.3 Hilal T, Sonbol MB, Prasad V. Analysis of control arm quality in randomized clinical trials leading to anticancer drug approval by the US Food and Drug Administration. JAMA Oncol 2019; 5: 887–92.bortezomib-containing regimen such as bortezomib, lenalidomide, and dexamethasone? What were the outcomes for those patients for the control and intervention?As crossover was allowed, 63 patients crossed over from bortezomib and dexamethasone to selinexor, bortez-omib, and dexamethasone at pro-gression. The investigators report that 49% of patients who crossed over did not get subsequent treatment. Is it ethical to permit patients to cross over to a triplet therapy containing two of the drugs that have already been administered many times before (especially if patients are unable to receive anything afterwards)? Was the receipt of highly effective agents, such as daratumumab, delayed?The results of this study should indeed change the practice of the medical community, and not because of the efficacy, safety, or novelty of selinexor. This study should change the practice of enrolling patients onto antiquated control groups that have already been repeatedly shown to be inferior.3VP reports royalties from Johns Hopkins Press, Medscape, and MedPage; consulting for UnitedHealthcare; speaking fees for Evicore; has a plenary session podcast that has Patreon backers; and is funded to study low-value drugs through a grant from Arnold Ventures. AG reports consulting for Seattle Genetics and EUSA Pharma. All other authors declare no competing interests.*Ghulam Rehman Mohyuddin, Al-Ola Abdallah, Brian McClune, Aaron Goodman, Vinay Prasadrehmanm@gmail.comDepartment of Hematological Malignancies and Cellular Therapeutics, Kansas University Medical Center Kansas City, KS 2350, USA (GRM, A-OA); Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT, USA (BM); Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA, USA (AG); Division of Hematology and Division of Medical Oncology, University of California San Francisco, San Francisco, CA, USA (VP)1 Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed multiple myeloma (RMM): results from the phase III study ENDEAVOR. J Clin Oncol 2015; 33: 8509.Sebastian Grosicki and colleagues1 reported the results of a randomised study among patients with pre-viously treated multiple myeloma comparing selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone. The primary endpoint was progression-free survival, and the investigators observed improved progression-free survival in the selinexor, bortezomib, and dexamethasone group. However, we are concerned about whether the presence of extramedullary plasmacytomas was well balanced between the two groups.The incidence of extramedullary plasmacytomas at the diagnosis of multiple myeloma has been reported as 16·3%.2 Previous research has shown that the presence of extramedullary plasmacytomas was significantly associated with a shorter progression-free survival in a retrospective study (median time 27 months vs 38 months, p=0·006),3 as well as in a longitudinal study (hazard ratio 1·46, p=0·04).4 Furthermore, radiation therapy is one of the most useful therapeutic options for extramedullary plasmacytomas,5 but Grosicki and colleagues1 did not mention radiation therapy for extramedullary plasmacytomas. As such, because patients with extra-medullary plasmacytomas have poorer progression-free survival than those without it, and require different treatment strategies, it might have skewed the study results if the presence and the radiation therapy of extramedullary plasmacytomas was not balanced between the two groups.Did the investigators observe improved progression-free survival among patients with extramedullary Authors’ replyWe thank Ghulam Mohyuddin and colleagues for their interest in our Article1 but respectfully disagree with their labelling of the bortezomib and dexamethasone group in our study as an inferior control group. First, according to their own definition, an inferior or suboptimal control group uses a treatment that is not standard of care, with standard of care being a treatment recommended by current guidelines and review papers.2 The bortezomib and dexamethasone doublet drug regimen is a standard-of-care treat ment for patients with relapsed or refractory multiple myeloma, because it is recommended by the 2021 edi tion of the National Comprehensive Cancer Network guidelines, by the current European Society for Medical Oncology guidelines, and by the current American Du Cane Medical Imaging Ltd/Science Photo Library

Multiple myeloma triplet therapies: baseline characteristics and control groups.

Abstract

Similar works

Full text

Available Versions

eScholarship - University of California