A MESSAGE FROM IMF LEADERSHIP

IMF Board of Directors

Brian G. M. Durie, MD

Chairman of the Board and Chief Scientific Officer, Professor of Medicine, and Hematologist/ Oncologist – Los Angeles, CA

Yelak Biru, MSc

IMF President & Chief Executive Officer – Los Angeles, CA

Susie Durie

IMF Founder & Director of Global Patient Initiatives – International Myeloma Foundation –Los Angeles, CA

Christine Battistini

President of International Myeloma Foundation Latin America and Instituto Espaço de Vida –São Paulo, Brazil

Dear Friends,

Dear Friends,

The International Myeloma Foundation (IMF) is the first and largest organization focusing specifically on myeloma. Our reach extends to more than 525,000 members in 140 countries. The IMF works to improve the quality of life of myeloma patients while working toward prevention and a cure through our four founding principles: Research, Education, Support, and Advocacy.

Amid a year of global setbacks, the IMF has been hugely successful in reaching out to the myeloma community through its educational and support programs, as well as myeloma expert collaborations and ongoing clinical research.

We are truly grateful to those who have made contributions in helping us provide education and support to myeloma patients, while keeping them safe from COVID-19. This has been one of our main focuses for the Fiscal Year 2022.

Of note, the IMF is proud to report our latest results in myeloma research. The Black Swan Research Initiative’s® ongoing projects continue to yield positive outcomes. Results of the ASCENT (Aggressive Smoldering Cure Evaluating Novel Therapies) Trial were presented at the 64th American Society of Hematology (ASH) Annual Meeting, showing 97 percent of patients having an overall response, with 84 percent having minimal residual disease (MRD) negative status. We are optimistic that a number of these patients will have sustained MRD-negative status and may end up indeed being cured by this early aggressive intervention. In addition, results of the CESAR Trial are similarly optimistic—63 percent of patients achieved MRD negativity after maintenance, with a 6-year survival rate that’s in the 90 percent range. Both trials require longer follow-up, but excellent long-term benefits are reasonably anticipated. Also, at the 2022 ASH Annual Meeting in New Orleans in December, a total of 10 abstracts on the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) Project were selected.

As always, our top priority is the well-being of myeloma patients everywhere. The IMF works every day to bring the myeloma community together to fight myeloma while keeping myeloma patients as safe as possible.

Today, the possibility of achieving a cure is closer than ever. Again, our warmest thanks to all our supporters for remaining with us in 2022. With myeloma patients as top of mind, the IMF moves forward with resilience and the goal of achieving the best outcomes for all.

Sincerely yours,

Mario Boccadoro, MD

Professor of Medicine, University of Torino – Torino, Italy

Loraine Boyle

Writer/Producer – New York, NY

Martine Elias, MSc

Executive Director Myeloma Canada – Montreal, Quebec

George T. Hayum, JD Entertainment Law –Los Angeles, CA

Jason Katz Growth Marketing –New York, NY

Benson Klein, JD

Attorney – Bethesda, MD

Andrew Kuzneski, III Investment and Banking –Indiana, PA

Robert A. Kyle, MD

Professor of Medicine –Hematologist/Oncologist Mayo Clinic – Rochester, MN

Professor Heinz Ludwig, MD Professor of Medicine, Wilhelminen Cancer Research Institute –Vienna, Austria

Edith P. Mitchell, MD Professor of Medicine –Philadelphia, PA

Your generosity and commitment to the International Myeloma Foundation (IMF) have helped us make a real difference in the lives of myeloma patients. As we reflect on the past year, I am proud to say that we have achieved many exciting milestones. Whether you are following or supporting IMF research, participating in a support group, advocating for cancer legislation, educating yourself and others through our publications or our InfoLine team, you are a part of our progress.

The Fifth Annual Asian Myeloma Network (AMN) Summit was held virtually. Many of the participating regions—Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand — have active myeloma associations or were inspired to begin forming them due to the summit. Also, the AMN has 10 clinical trials in progress, and 11 of its member countries are collaborating for myeloma patients to have increased access to treatments and an improved quality of life.

At the 63rd American Society of Hematology (ASH) Annual Meeting, the IMF presented 10 abstracts on the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) project. This population-based screening, which enrolled over 80,000 participants, is the first of its kind: the largest randomized trial that has ever been conducted in any type of cancer research.

In addition to research, the IMF continued to promote health equity worldwide. Our Nurse Leadership Board (NLB), Global Myeloma Action Network (GMAN) and the M-Power Initiatives have been actively involved in initiatives aimed at reducing disparities in healthcare access and treatment outcomes for underrepresented communities.

As a nonprofit organization with a global presence, the IMF has always prioritized collaboration and knowledge-sharing among experts worldwide. The 13th International Myeloma Working Group (IMWG) Summit, which took place in-person in Vienna in June 2021, was a testament to this effort. Researchers shared their most promising findings to prevent the onset of active disease, and to improve myeloma treatments, with the goal of finding a cure for myeloma.

Having joined the IMF as President and CEO in late 2021, I have closely observed the comradery, commitment, and contributions of our entire myeloma community. We are so grateful for your continued support of the IMF and our mission. Without you, we would not be able to continue this crucial work. As a 27-year myeloma patient, and the President and CEO of the IMF, I am honored to be part of these remarkable efforts. Together, we will continue to make strides in research, education, support, and advocacy, bringing more hope to the world, and ultimately, finding a cure for myeloma.

Sincerely yours,

IMF Executive Team

Yelak Biru, MSc President & Chief Executive Officer

Brian G.M. Durie, MD Chief Scientific Officer, Professor of Medicine, and Hematologist/Oncologist

Jennifer Scarne Chief Financial Officer

IMF Staff

Betty Arevalo Manager, Inventory Control

Nancy Bruno Director, Support Groups

Sarah Chambliss Project Manager, Medical Meetings

Kelly Cox Director, Support Groups & Senior Director, Regional Community Workshops

Danielle Doheny Director, Public Policy & Advocacy

Susie Durie Director, Global Patient Initiatives

Diane Moran Senior Vice President, Business Relationship Management

Lisa Paik Executive Vice President, Research Operations

Daniel Navid Senior Vice President, Global Affairs

Serdar Erdoğan Director, GMAN and European & Middle Eastern Patient Programs

Jon Fitzpatrick Technology & Coordinator, Support Groups

Sherrie Guerrero Director, Human Resources

Paul Hewitt Coordinator, InfoLine

Kevin Huynh Web Specialist

Katie Ives Administrative Assistant, Meetings

Marya Kazakova Editor-in-Chief, Publications

Joseph R. Mikhael, MD Chief Medical Officer

Lynn K. Green, Ed.D. Senior Vice President, Philanthropy

Mimi Choon-Quinones, PhD, MBA, LLM

Senior Vice President, Global Advocacy, Access, Policy & Research

Ilana Kenville Assistant Director, Distinguished Events

Missy Klepetar Coordinator, InfoLine

Sapna Kumar Marketing Strategist

Phil Lange Accountant

Karla Lemus Donor Relations Specialist

Jason London Manager, Marketing & Communications

Jim Needham Publication Design

Charles Newman, MS

Entrepreneur – Ann Arbor, MI

S. Vincent Rajkumar, MD Professor of Medicine

Mayo Clinic – Rochester, MN

Matthew Robinson, MBA Owner/General Manager Swift House Inn – Middlebury, VT

E. Michael D. Scott Communication Strategist –Philadelphia, PA

Brian G.M. Durie, MD

Chairman, IMF Board of Directors | Chief Scientific Officer

Yelak Biru, IMFPatient, President and CEO

Peter Anton Vice President, Marketing

Robin Tuohy Vice President, Support Groups

Meghan O’Connor Meeting & Project Manager, Content & Communication

Selma Plascencia Director, Operations

Annabel Reardon Senior Director, Program Operations & Chief of Staff

Joy Riznikove Database Analyst

Miko Santos Web Producer

Narmeen Shammami Senior Research Project Coordinator

Sarah Solomon Donor Relations

Brando Sordoni Accounting & Distribution

Rafi Stephan Assistant to the President & Chief Executive Officer

Daria Tabota Coordinator, Marketing & Communications

Deborah Verla Coordinator, InfoLine

Jonathan Weitz Donor Relations

Haleigh Wolfe Project Manager

THE INTERNATIONAL MYELOMA FOUNDATION DRIVES THE ORGANIZATION FORWARD

While

KEEPING PATIENTS AT THE CENTER OF EVERYTHING WE DO

The IMF’s approach is holistic, diverse, and deep. The Foundation supports and educates the myeloma community as well as advocates for those who cannot advocate for themselves. Our research initiatives are consistently innovating; we are finding methods to prevent disease progression, monitor and improve treatments, accelerate drug development, and improve patient outcomes. The IMF would not be able to do this important work without the generous donations and time of people like YOU.

Here are just some of the ways that YOU helped the IMF excel at improving the quality of life of myeloma patients while working toward prevention and a cure:

THE BLACK SWAN RESEARCH INITIATIVE® (BSRI) TEAM HAS DEVELOPED A PRECISE METHOD FOR DEEP RESPONSE ASSESSMENT

To track myeloma at very low levels of disease, sensitive, reliable, standardized, and affordable testing is required. Such methods can detect Minimal Residual Disease (MRD). Under the leadership of Alberto Orfao, MD, PhD (University of Salamanca — Salamanca, Spain), Spanish BSRI team members have developed a new method using flow cytometry, a widely available laboratory technique.

Passing bone marrow cells through the flow cytometer, a combination of eight monoclonal antibodies were used to detect even one out of a million cells as myeloma cells (with a sensitivity at the 10 to -6 level). This method was called Next Generation Flow (NGF) and includes a specialized software package which automates the myeloma cell detection process. This method has now been developed at the commercial level, and FDA approval is expected during 2023. The BSRI team continues to enhance MRD testing. Using an immunomagnetic bead approach, team member Bruno Paiva, PharmD, PhD (University of Navarra — Pamplona, Spain.) has been able to improve sensitivity to the 10 to –8 level, which detects one out of 100 million cells. testing is essential to assess the true added value of these many new therapies and combinations.

This level of sensitivity enables MRD monitoring using blood samples rather than bone marrow. A huge advantage for patients, this method can detect myeloma cells from bone marrow and from any soft tissue or area of myeloma outside the bone marrow (which is known as extramedullary disease).

THE IMF CONTINUES TO INNOVATE FOR MYELOMA PREVENTION WITH THE iSTOPMM PROJECT AND ONGOING “CURE” TRIALS

Read about these innovative trials focused on prevention and cure on pages 8 and 9 of this Annual Report.

The Imf Funds Junior And Senior Researchers

The IMF continues to fund leading researchers from around the globe. By funding researchers early in their careers, the IMF is inspiring the brightest minds to study myeloma, embark on innovative projects, and become future experts in the field. This past year’s grant award recipients are highlighted on page 13 of this report.

THE IMF’S INTERNATIONAL MYELOMA WORKING GROUP (IMWG) HAS DEVELOPED A VIRTUAL BIOBANK

The Imf Has Developed An Immune Therapy Registry

The IMF’s immune therapy registry is electronically housed at the University of California in San Francisco and serves as a valuable resource of real-world data for patients, investigators, and pharmaceutical partners around the globe. This real-world registry captures information about the benefit and possible side effects or toxicities of therapies in a community setting for patients who are being treated by their own local doctors. Information is gathered in an ongoing and sequential fashion. The goal is to understand how these treatments work in real-world situations and what difficulties (if any) may arise from using these therapies.

The Imf Is Committed To Health Equity And Removing Barriers To Care Based On Racial And Ethnic Differences

These exciting developments in MRD testing mean that early response assessments can shorten times in clinical trials and bring data forward for FDA review and approval much faster. More rapid treatment development like this reduces costs as well.

For the individual patient, documentation of deep response illustrates the remarkable benefits with the many new therapies such as immune therapies, producing sustained MRD undetected outcomes. Precise MRD

Tissue samples (such as bone marrow and blood samples) are collected from patients undergoing treatment, particularly the newer immune therapy treatments. The purpose is to better understand the mechanisms of why some patients respond while others do not. In a virtual biobank, all samples are collected, kept, and tested in a local setting with the results entered in a computer and submitted electronically for storage and analysis. Researchers are thereby able to conduct the most significant testing for their patient populations.

The IMF recognizes disparities in healthcare exist, which are preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations. We will proactively work toward health equity, and we will aspire to ensure that every person has the opportunity to attain his or her full health potential and that no one is disadvantaged from achieving this potential because of social position or other socially determined circumstances. Read more about the IMF’s M-Power Project, which focuses on health equity for all, on page 15 of this report.

With your support, the IMF team forges forward. The goal is to use past learnings to inform future efforts, and most importantly, as the IMF’s President and CEO Yelak Biru (who is a myeloma patient himself) says, “Keep the patients at the center of everything we do.”

UPDATE ON THE IMF’S BLACK SWAN RESEARCH INITIATIVE’S ISTOPMM PROJECT

The Black Swan Research Initiative® (BSRI) has over 50 ongoing projects worldwide. Here are some highlights:

The U.S.-based ASCENT Trial (Aggressive Smoldering Cure Evaluating Novel Therapies) uses a combination of carfilzomib, lenalidomide, dexamethasone, and daratumumab in high-risk smoldering multiple myeloma. The results of this trial were presented at the American Society of Hematology (ASH) Annual Meeting in December 2022 by Dr. Shaji Kumar from the Mayo Clinic, who leads this BSRI protocol. They showed that 97% of patients had an overall response in this treatment protocol and that 84% had minimal residual diseasenegative status.

According to IMF Chairman of the Board and Chief Scientific Officer Dr. Brian G.M. Durie, “We are quite optimistic that a number of these patients will indeed have sustained MRD-negative status and may end up indeed being cured by this early aggressive intervention.”

The CESAR Trial has a longer-term follow-up and uses Kyprolis (carfilzomib), Revlimid (lenalidomide), and dexamethasone (KRd) plus autologous stem cell transplant (ASCT) rather than daratumumab in the same setting as the ASCENT trial. Its results were very similar to ASCENT, with 63 percent of patients achieving MRD negativity after maintenance (a little less as compared to the ASCENT trial). With almost 6 years of follow-up (70.1 months), 5 patients have progressed with 94 percent of patients still in remission. Thus far, only 7 patients have died— giving a 6-year survival rate that’s also in the 90 percent range. Longer follow-up is required for both trials, but it is reasonable to anticipate excellent long-term benefits.

The IMF’s iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) project is a population-based screening study for monoclonal gammopathy of undetermined significance (MGUS) led by Dr. Sigurður Kristinsson (University of Iceland, Reykjavík, Iceland). iStopMM examines the population of Iceland, where everyone over the age of 40 was invited to participate in the study and more than half of this population volunteered. The diverse outcomes from iStopMM will benefit both the myeloma community in Iceland and around the world.

A total of 10 abstracts on iStopMM were selected for presentation at the 64th American Society of Hematology Annual meeting in December 2022:

Abstract #103 demonstrates that while prevalence of MGUS is high in the iStopMM study, the prevalence of IgA MGUS does not increase with age in the way other immunoglobulin subtypes do. Abstract #105 showed that

SARS-Cov-2 vaccinations do not lead to progression of MGUS. Abstract #967 looks at the epidemiology, causes, and the impact of using mass spectrometry in the detection and identification of M-proteins. The notion that the development of a new M-protein can be either temporary or transient was assessed as related to low-level proteins detected using mass spectrometry. Abstract #107 discusses the development of a multivariable model to predict the risk of ≥ 10% bone marrow plasma cells, which changes the diagnosis from MGUS to SMM. ASH attendees were extremely engaged with this abstract. The need for upfront bone marrow sampling in individuals with MGUS was based on four predictors: MGUS isotype (IgG, IgA, biclonal), M-protein concentration, free light chain ratio, and total concentrations of IgG, IgA, and IgM. Using this risk model, it became possible to avoid bone marrow sampling in 36.1% percent of patients. From a screened cohort of 75,422 persons age ≥ 40 years (51%of the Icelandic population), MGUS has been identified in 3,358 cases, of which 2,542 were randomized to active follow-up.

A calculator app has been developed and can be accessed at istopmm.com/riskmodel. Patients’ laboratory results can be entered to obtain an output of the predicted percent of plasma cells in the bone marrow. Patients and treating doctors can use these results to decide the best approach for each individual patient while considering factors such as age, cost, and preference.

Also, iStopMM presented 6 posters at ASH, which are reported on in the Winter 2023 edition of Myeloma Today. Collectively, these abstracts point to new paradigms in the evaluation and management of M-protein disorders. This new era of study looks at precursors to myeloma or other lymphoproliferative disorders. Visit myeloma.org/black-swan-researchinitiative/istopmm to learn more.

SOME HIGHLIGHTS OF BSRI PUBLICATIONS FROM FISCAL YEAR 2022

Minnema MC, Jacobs JFM. In response to: Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: results of the iStopMM study. Blood Cancer J. 2022 Nov 14;12(11):152. doi: 10.1038/s41408-02200751-0. PMID: 36376268.

Long TE, Indridason OS, Palsson R, Rognvaldsson S, Love TJ, Thorsteinsdottir S, Sverrisdottir IS, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdottir I, Olafsson I, Thordardottir AR, Eythorsson E, Jonsson A, Gislason G, Olafsson A, Steingrimsdottir H, Hultcrantz M, Durie BGM, Harding S, Landgren O, Kristinsson SY. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study. Blood Cancer J. 2022 Sep 14;12(9):133. doi: 10.1038/s41408-02200732-3. PMID: 36100605; PMCID: PMC9470548.

Sigurbergsdóttir AÝ, Love TJ, Kristinsson SY. Autoimmunity, Infections, and the Risk of Monoclonal Gammopathy of Undetermined Significance. Front Immunol. 2022 Apr 28;13:876271. doi: 10.3389/fimmu.2022.876271. PMID: 35572590; PMCID: PMC9096784.

Rögnvaldsson S, Long TE, Thorsteinsdottir S, Love TJ, Kristinsson SY. Validity of chronic disease diagnoses in Icelandic healthcare registries. Scand J Public Health. 2021 Dec 13:14034948211059974. doi: 10.1177/14034948211059974. Epub ahead of print. PMID: 34903105.

Rognvaldsson S, Eythorsson E, Thorsteinsdottir S, Vidarsson B, Onundarson PT, Agnarsson BA, Sigurdardottir M, Thorsteinsdóttir I, Olafsson I, Runolfsdottir HL, Helgason D, Emilsdottir AR, Agustsson AS, Bjornsson AH, Kristjansdottir G, Thordardottir AR, Indridason OS, Jonsson A, Gislason GK, Olafsson A, Steingrimsdottir H, Kampanis P, Hultcrantz M, Durie BGM, Harding S, Landgren O, Palsson R, Love TJ, Kristinsson SY. Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study. Blood Cancer J. 2021 Dec 1;11(12):191. doi: 10.1038/s41408-021-005807. PMID: 34853309; PMCID: PMC8635472.

Research

Paul Richardson (Dana-Farber Cancer Institute—Boston), Thierry Facon (Centre Hospitalier Universitaire de Lille— Lille, France) held a session on frontline therapy. Of note was the discussion on the MAIA regimen as being very effective and well-tolerated. This regimen for nontransplant eligible patients (such as the elderly and frailer) uses the three-drug combination of Darzalex, Revlimid, and dexamethasone.

CAR T-cell therapy was touched upon by Tom Martin, MD (University of California San Francisco—San Francisco); Yi Lin, MD, PhD (Mayo Clinic—Rochester, MN); and Mario Boccadoro, MD (University of Turin—Turin, Italy). They pointed out that the outcomes of trials such as CARTITUDE-5 and CARTITUDE-6, which are evaluating CAR T-cell therapy in the transplant-eligible (TE) and non-transplant-eligible (NTE) patient populations, are still needed for further assessment of CAR T.

INTERNATIONAL MYELOMA WORKING GROUP’S MILESTONES IN 2022

The IMF hosted the 13th Annual International Myeloma Working Group (IMWG) Summit in-person from June 7–9, 2022 in Vienna, Austria. More than a hundred IMWG members participated in this first in-person summit in two years. Its mission is to identify, support, and implement the most promising research to prevent the onset of active disease, to improve treatment, and to find a cure.

The following myeloma experts led these sessions at the Summit:

Sigurdur Kristinsson, PhD (University of Iceland— Reykjavik, Iceland) gave a presentation on “Is Screening the Way to Go?” where he summarized the results of the Black Swan Research Initiative® (BSRI)-supported iStopMM (Iceland Screens, Treats, Or Prevents Multiple Myeloma) Project. The project has already screened more than 80,000 individuals. Although the study’s results look promising, the consensus is that the outcome of the iStopMM randomized clinical trial must be awaited to be able to assess improvements in overall survival (OS) and quality of life. It does seem that screening will be one way forward in 2026.

Bruno Paiva, PharmD, PhD (CIMA Universidad De Navarra—Pamplona, Spain) evaluated if simple precise testing is needed to identify high-risk smoldering multiple myeloma (HR SMM) and explained why the answer is yes.

María-Victoria Mateos, MD, PhD (University Hospital of

Salamanca—Salamanca, Spain) discussed the results of various treatments for high-risk smoldering multiple myeloma (HR SMM), particularly the CESAR trial.

Jesús San Miguel, MD, PhD (Clínica Universidad de Navarra—Pamplona, Spain) chaired the session on assessing the current status of MRD testing. During the session, Alberto Orfao, MD, PhD (University of Salamanca—Salamanca, Spain) noted that using either next-generation flow (NGF) or next-generation sequencing (NGS) testing methods with negativities at the 10-5 to 10-6 levels is the most important. Hervé Avet-Loiseau, MD, PhD (University Cancer Center of Toulouse—Toulouse, France) emphasized that the MRD endpoint should be considered as a “stand-alone” indicator to establish the best correlations, especially at the 10-5 to 10-6 levels of sensitivity.

In Dr. San Miguel’s presentation, he cautioned about the required link to decisions for individuals identified as MRD-positive versus MRD-negative. Technical difficulties need to be standardized while low-level MRD positivity can be linked to a good outcome. These patients should possibly be identified on the basis of an MGUS-like phenotype on flow testing which indicates a very good prognosis, and more importantly, NO need for more potentially toxic therapy.

Drs. S. Vincent Rajkumar (Mayo Clinic—Rochester, MN),

Drs. Philippe Moreau (Nantes University Hospital—Nantes, France), Nikhil Munshi (Dana-Farber Cancer Institute— Boston), and Kenneth Anderson (Dana-Farber Cancer Institute—Boston) closed the sessions with discussions on treatments for early and late relapse. A special focus was on the new IMWG initiatives to establish an immune therapy database and a virtual tissue biobank.

Other highlights of the Summit included the presentation of the IMF’s 21st Annual Robert A. Kyle Lifetime Achievement Award to Dr. Hervé Avet-Loiseau, Head of the Laboratory for Genomics in Myeloma at the University Hospital Center of Toulouse and Head of the Hematology Laboratory at the University Hospital of Nantes in France.

The Brian G.M. Durie Outstanding Achievement Award, recognizing excellence in myeloma research, was awarded to Dr. Bruno Paiva, co-director of the Flow Cytometry Platform and co-director of the Monoclonal Gammopathies Research Laboratory at the CIMA Universidad De Navarra in Pamplona, Spain, with preferential dedication to multidimensional flow cytometry analysis of hematological malignancies.

Dr. Paiva is also a key member of the i2TEAMM, which seeks U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals for MRD testing as a surrogate response endpoint in myeloma clinical trials.

As is tradition with the Summit, the myeloma experts broke out into working group committees and discussed the following topics:

• Plans to establish a virtual computer database for imaging studies for bone disease in Roswell Park Comprehensive Cancer Center in Buffalo, NY The ability of mass spectrometry (MS or “mass spec”) to detect and track monoclonal myeloma proteins at very low levels as a major step forward, with a fully commercialized mass spec product eagerly awaited.

Imwg Publications In Fiscal Year 2022

Raje N, Munshi N et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group

Lancet Haematol 2022 Feb;9(2):e143-e161. doi: 10.1016/S23523026(21)00283-0.