DOCTORS of Amyloidosis

1. DOCTORS ofAmyloidosis Amyloidosis is a rare disease that occurs when a substance called amyloid builds up in yourorgans. Amyloid is an abnormal protein that is produced in your bone marrow and can be deposited in any tissue or organ. Amyloidosis can affect different organs in different people, and there are different types of amyloid. This disease frequently affects the heart, kidneys, liver, spleen, nervous system and digestivetract. Severe amyloidosis can lead to life-threatening organ failure. Each doctor in this video is in the fight against thisdisease. This is their messagetoyou. (Shown alphabetically by lastname.) www.mm713.org/doctors-of-amyloidosis/

2. DOCTORS ofAmyloidosis • Angela Dispenzieri,M.D. • Mayo Clinic, Rochester,MN • Consultant, Divisionof Hematology Amyloidosis refers to a group of diseases which share amyloid deposits in body tissues. Fortunately, we are making significant progress with better treatments and earlier diagnoses. Unfortunately, progress is not fast enough for manypatients. Although research and development of new drugs is exceedingly important, early diagnosis is as important, especially in the case of immunoglobulin light chain (AL)amyloidosis. The explosion of new drugs for multiple myeloma will continue to offer more options for patients with AL amyloidosis. In addition, the progress for patients with ATTR amyloidosis with 2 drugs (Inotersen and Patisiran) approved for patients with peripheral neuropathy due to ATTRmt amyloidosis (hereditary or familial) is unprecedented. These same drugs will likely be effective (and hopefully safe) for patients with cardiac ATTR whether it is hereditary (ATTRmt) or age related (ATTRwt). Next year we anticipate the first drug for ATTR cardiomyopathy to be approved (Tafamadis). Here is to progress and moreprogress! www.mm713.org/doctors-of-amyloidosis/

3. DOCTORS ofAmyloidosis • Morie A. Gertz, M.D.,M.A.C.P. • Mayo Clinic, Rochester,MN • Chair, InternalMedicine • Consultant, Divisionof Hematology Amyloidosis is a very rare disease. Its symptoms mimic more common disorders and as a consequence the diagnosis isdelayed. Delay of diagnosis due to failure to recognize remains a major barrier to improving outcomes in patients with thisdisorder. Widespread educational efforts to alert the Medical Community to the symptoms and signs associated with this disorder are essential to ensure earlier diagnosis which inevitably will translate into betteroutcomes. Steps are underway to insert into the daily work flow appropriate diagnostic testing that will alert specialists in the treatment of heart, kidney and nerve disorders to this devastatingdisorder. The past five years have shown enormous improvements in the outcomes of these patients with the introduction of new therapy. Trials are underway looking at antibodies capable of dissolving the amyloiddeposits. www.mm713.org/doctors-of-amyloidosis/

4. DOCTORS ofAmyloidosis • Martha Grogan,M.D. • Mayo Clinic, Rochester,MN • Founder and Director ofthe Cardiac AmyloidClinic • Consultant, Division of CardiovascularDiseases The most important thing for others to know about amyloidosis is that it is not nearly as rare as previously thought. It is so exciting that we now have rapidly expanding treatment options for both AL and ATTR amyloid! We hope that new options will be forthcoming for the more rare types, aswell. The advent of treatment has caused huge enthusiasm, particularly in the general cardiology community. All types of amyloid will be increasingly diagnosed: this is no longer an “academic”disease. For ATTR amyloid, we are on the verge identifying techniques to allow for early diagnosis and intervention. For the first time ever, we may have treatments that will truly prevent amyloidosis and its consequences, especially heart failure. It is important for even those considered to be “amyloid experts” to be humble about this disease. Every day we are learning something new, seeing a new variation on the theme and seeing something that might have been said to “never” occur in the past. Our patients are the most valuable of source of our knowledge of amyloidosis. We are deeply grateful to their observations as they help us advanced the science and find effective treatment. The more we learn, the more we realize that we do not know. But that’s exactly the way it should be and we need to keep pushing the frontiersforward! www.mm713.org/doctors-of-amyloidosis/

5. DOCTORS ofAmyloidosis • James E. Hoffman,M.D. • University ofMiami HealthSystem • InternalMedicine • CancerTreatment It is an exciting time for those of us that treatAmyloidosis. Given the continued advances in the treatment of Multiple Myeloma we continue to get new treatments for AL Amyloidosis, both more effective and more tolerable. We are seeing better responses, more rapid improvement in symptoms and better quality of life. In ATTR amyloidosis, we now have multiple medicines we can use to slow the disease, particularly for hereditarydisease. Given the ability to finally treat this underdiagnosed condition, and therefore, doctors are more aggressive about investigating this possibility for patients. We expect to diagnose more people earlier in their illness, and see improved outcomes. This remains a difficult condition, that can be confusing to diagnose, but the future continues to brighten, and the Amyloidosis clinic has therefore becomes a steadily more optimisticplace! www.mm713.org/doctors-of-amyloidosis/

6. DOCTORS ofAmyloidosis • Daniel Judge,M.D. • Medical University of SouthCarolina • Professor ofMedicine/Cardiology • Director, CardiovascularGenetics Among the many etiologies for amyloidosis, I'm only aware of one whose cause is completely unknown - "wild-type TTR amyloidosis" or ATTRwt. It's sometimes attributed to age and gender, but I and other specialists in the field are aware of many exceptions to these general risk factors. There are projects underway to try to understand this condition better. My lab is working on genetic investigation, to see if genes other than TTR may be abnormal for people with thiscondition. Second, there are some clues from environmental and lifestyle factors, which may contribute to this condition. I hope and expect that new insights will be available soon. One goal from this work is to identify people who are at highest risk of developing amyloidosis, and stopping it from gettingworse. Another major question in this field is focused on how this condition varies among people with amyloid. For instance, some people with AL (light chain) amyloid have cardiomyopathy and normal kidneys/nerves. Others have only neuropathy, and some others have amyloid primarily in their kidneys. At this point, it's not clear why some amyloid protein deposits in these parts of the body selectively for some people, and others have different manifestations. Research investigating these differences may help to understand this better, and ideally also help to prevent amyloid from depositing in different parts of thebody. I think it's worthwhile to point out that heart biopsies are usually very easy. In comparison with a "cardiac catheterization," which involves dye and some small risk of a stroke, a heart biopsy can be done with much lower risk. After heart transplantation, cardiac biopsies are done frequently, and usuallywithout www.mm713.org/doctors-of-amyloidosis/

7. DOCTORS ofAmyloidosis sedation (since they don't hurt). Fortunately, improved imaging techniques sometimes make a biopsy unnecessary. However, when a biopsy is necessary, I rate heart biopsies as easier to experience than bone marrow biopsies, kidney biopsies, and rectal biopsies. Fat pad "aspirates" (needle under the skin to remove some fat) are even easier, but they often don't make the diagnosis. If that fails, don't be afraid to have a heartbiopsy. www.mm713.org/doctors-of-amyloidosis/

8. DOCTORS ofAmyloidosis • Heather J. Landau,M.D. • Memorial SloanKettering CancerCenter • Oncologist • Hematologist When asked what I wanted others to know about amyloidosis, there was no hesitation. I want patients and doctors to know — that there is HOPE … and a lot ofit! The amount of progress that has been made in the last decade is incredible. This year alone, we witnessed the first two FDA approved drugs, Patisiran and Inotersen, for polyneuropathy caused by hereditary transthyretin amyloidosis (hATTR). In addition, it is expected that Tafamidis which was studied in both mutated (hATTR) and non-mutated (wtATTR) transthyretin-associated amyloidosis causing heart failure will be approved any time now. This is very exciting because while other forms of amyloidosis are relatively rare, non- mutated (or wild-type) transthyretin amyloidosis is found in a substantial proportion of the aging population, with 25% of octogenarians afflicted. We are also able to diagnose patients with this condition more easily and non-invasively, without necessarily subjecting patients to biopsies. For patients with light chain (AL) amyloidosis, antibodies that target the plasma cells are being studied and appear to be uniquely effective and extremely well tolerated. While removing amyloid from organs isn’t currently readily achievable, several strategies are being studied which hold promise. It is entirely possible that this will become a reality. So, the message from where I sit is that there is hope for patients with amyloidosis. Many brilliant and dedicated scientists and clinical researchers are working together with passionate advocacy groups to facilitateawareness, www.mm713.org/doctors-of-amyloidosis/

9. DOCTORS ofAmyloidosis promote early diagnosis and bring treatments to patients. This collaboration and patient participation in clinical trials is essential to push the field forward and it ishappening. www.mm713.org/doctors-of-amyloidosis/

10. DOCTORS ofAmyloidosis • Mathew S. Maurer,M.D. • Columbia UniversityMedical Center • Advanced Heart Failureand Transplant Cardiology, Internal Medicine, Cardiovascular Disease I want my colleagues to know that amyloidosis is not as rare as one thought. If they start to think “could this be amyloidosis?” the chance of missing the diagnosis will decline considerably. Indeed, it is an easy to diagnose, if you just think about it. I also want them to know that it is treatable, and treatments are especially effective if given early. Most providers have said previously that they have never seen a case of cardiac amyloidosis or have only seen one. This means that they have missed a whole lot of affected patients with potentially devastatingconsequences. I believe the progress made in the evaluation, diagnosis and treatment for transthyretin cardiac amyloidosis can be a model for addressing many of the conditions that disproportionately afflict older adults. The field of geroscience has the potential to elucidate the mechanisms underlying age related disorders such as proteostasis with the potential to dramatically improve the quality and quantity of our lives. Such discovery and progress will require continued investment by the NIH, with the rewards of such investment beinggreat. I want others to know that patients with amyloidosis are really special folks who suffer from a chronic and potentially devastating condition and plug along with the help, support and love from their wonderful families and caregivers. I am privileged to be a part of their lives and amazed by theirfortitude. www.mm713.org/doctors-of-amyloidosis/

11. DOCTORS ofAmyloidosis • Jose Nativi-Nicolau,M.D. • University of Utah Health& Huntsman CancerInstitute • Assistant Professorof Medicine • Cardiovascular Directorof the AmyloidosisProgram The suspicion of amyloidosis (e.g., echocardiogram, magnetic resonance or symptoms) is a medical emergency. The estimated one-year survivalrate for stage IV light chain amyloidosis is only 30%, which is much lower compared to stage IV colon cancer 50% and stage IV breast cancer 52%. A diagnostic evaluation should be completed in 1-2 weeks. There is no time tolose. It only takes 10 seconds to ask patients about carpal tunnel orback surgeries. These 10 seconds can prolong the life of patients with amyloidosis for severalyears. Hope has arrived for patients with amyloidosis, as novel therapeutic agents have demonstrated improved survival and quality oflife. However, patients that are diagnosed earlier have the mostbenefit. www.mm713.org/doctors-of-amyloidosis/

12. DOCTORS ofAmyloidosis • Frederick L. Ruberg,M.D. • - Boston University Medical Center & School ofMedicine • Associate Professor of Medicine andRadiology • Section ofCardiovascular Medicine • Department ofMedicine Doctors have a lot of work to do to educate our colleagues about amyloidosis. We need to teach medical students and clinicians that amyloidosis is not just a disease they read about in textbooks, but one they likely see on a regular basis. We must explain that amyloidosis is now treatable and that prompt recognition of patients with early-stage amyloidosis is critical because treatments are most effective when administeredearly. We must first develop and then encourage widespread adaptation of screening algorithms that clinicians can utilize to recognize new cases. Unfortunately, at the present time, we know that many patients wait too long and see too many doctors before receiving the right diagnosis, and this mustchange. I think patient self-education is very challenging given the amount of incorrect information that abounds on the web. One of the great values of the Amyloidosis Research Consortium, the Amyloidosis Foundation, and Amyloidosis Support Groups is that they provide accurate medical information that is accessible to patients. We are fortunate to have theseresources. Finally, while we greet each new drug treatment for amyloidosis with enthusiasm, we need to work with drug makers and insurers to bring these needed treatments to our patients in a manner all canafford. www.mm713.org/doctors-of-amyloidosis/

13. DOCTORS ofAmyloidosis • Vaishali Sanchorawala,M.D. • - Boston MedicalCenter • Professor ofMedicine • Director,Amyloidosis Center • Director, AutologousStem Cell TransplantProgram We are at an epic moment in the treatment of systemic amyloidosis. The therapeutic landscape of AL and ATTR amyloidosis is rapidly and widely expanding. Now the challenge is on the healthcare providers to diagnose this rare disease sooner before vital organs are severely affected anddamaged. We all play a role in increasing awareness of this devastating disease of the 1980s and 1990s. Let us join forces to increase awareness and improve diagnosis, so that many patients can be offered contemporary novel therapies to halt progression of disease and improve outlook of patients andcaregivers. Exciting times are ahead and educating community physicians is crucial. I am honored to be a witness to our trainees learning and growing beyond the Amyloidosis Center; our faculty becoming empowered thought leaders in the field of amyloid diseases; and to our friends and family like you building a stronger Amyloidosis Awareness Campaign every day. www.mm713.org/doctors-of-amyloidosis/

14. DOCTORS ofAmyloidosis • Taimur Sher, M.D.,M.B.B.S. • Mayo Clinic, Jacksonville,FL • Hematology • InternalMedicine • Oncology There has never been a better time to be diagnosed and dealing with amyloidosis than today. Last 10 years have seen in remarkable increase in our understanding about the biology of various types of amyloidosis. This is evident by exponential increase in the number of publications related to amyloidosis and that one of the Keystone lectures of 2017 American society of Hematology meeting was devoted to amyloidosis. Tremendous advancements have been made for the diagnosis and treatment of 2 most common types of systemic amyloidoses, i.e., ATTR and AL. In 2018 two novel treatments Inotersen and Patiseran were approved for the treatment of familial amyloid neuropathy (FAP) TTR amyloidosis. Their use is expected to be expanded to familial amyloid cardiomyopathy as well. Spindle stabilizer tafamidis has shown benefit in patients with amyloid cardiomyopathy in a randomized placebo controlled clinical trial and is expected to be available to patients in near future. The genetic testing and counseling has become more widely available for family members and relatives of patients with familialATTR. In AL amyloidosis bortezomib, cyclophosphamide and dexamethasone has become a standard combination for initial treatment of patients. Amonoclonal www.mm713.org/doctors-of-amyloidosis/

15. DOCTORS ofAmyloidosis antibody, daratumumab that targets the cancerous plasma cells-the source of amyloidogenic light chains-has shown remarkable activity even as single agent with benefits noted a even in patients who had disease resistant to otherwise very effective treatment such as bortezomib and lenalidomide. Its use in combination with other medications such as bortezomib is being evaluated in a phase 3study. A key point to remember is that in AL amyloidosis supportive care forms of cornerstone of treatment. Even though the treatment works very effectively in “shutting down the factory”- the cancerous plasma cells- it has side effects which can at times be very challenging especially given the fact that various organs unaffected byamyloidosis. I would like to thank all patients and families who participated in the clinical trials of NEOD-001. Even though it was disappointing to note that the drug did not meet its expectation, we certainly learned that overall patients did significantly better than expected based on historical data-indicating that treatments over the last several years are already making difference in life expectancy ofpatients. The motivation and drive shown by patients and families dealing with amyloidosis and the Amyloidosis Support Group has clearly put this disease on the map-I see that in the very near future we will be able to see the impact of these advancements and developments in patients living a better and longer lifewith goodquality. www.mm713.org/doctors-of-amyloidosis/

16. DOCTORS ofAmyloidosis Jeffrey Zonder,M.D. - Karmanos CancerCenter - Department ofOncology Amyloidosis, for me, started out as a simple byproduct of having a multiple myeloma clinic. A case of AL amyloidosis misdiagnosed as myeloma. A case of myeloma complicated by coexisting amyloidosis. A case of bilateral carpal tunnel syndrome in a person with MGUS that nobody ever really looked into. And, as if by fate, right as I realized I needed to know a lot more about this than I did, we got a call asking whether our institution wanted to host a standing amyloidosis supportgroup. For me, sitting in on this was transformative, because it was at that first meeting, listening to over a dozen patients talk with each other and a visiting amyloidosis expert about their individual journeys with amyloidosis, I started to understand the complexity and variability of the disease. In the 10 years since that first meeting, even as I have worked to build a clinical research program focusing on amyloidosis, I continue to regularly attend amyloidosis supportgroups. I never cease to learn from amyloidosis patients and their families, and it is grounding to hear theirexperiences. www.mm713.org/doctors-of-amyloidosis/

17. DOCTORS ofAmyloidosis If an amyloidosis-focused researcher ever really wants to understand what a victory like a new drug approval or a setback like the shuttering of a research program due to negative trial results really means to patients in the amyloidosis community, my best advice is to sit down and spend a Saturday morning with a bunch of them and justlisten. www.mm713.org/doctors-of-amyloidosis/

18. DOCTORS ofAmyloidosis Be a voice, notan echo. AlbertEinstein There is nocure. We aim to changethat. www.mm713.org/doctors-of-amyloidosis/