In recognition of Multiple Myeloma Awareness Month, Healio Education Lab interviewed Kenneth Anderson, MD to find out what the future may hold for patients with the disease. Watch the video below for our exclusive interview; a transcript of the interview is also provided.
Kenneth Anderson, MD
Kraft Family Professor of Medicine,
Harvard Medical School;
Director of the Jerome Lipper Multiple Myeloma Center
and Lebow Institute for Myeloma Therapeutics,
Dana-Farber Cancer Institute
Dr. Anderson: Multiple myeloma is a bone marrow cancer not unlike leukemia. It’s characterized by excess bone marrow plasma cells and monoclonal protein in the blood and urine made by those plasma cells. Patients can develop kidney disease, high blood calcium, anemia, bone disease, and other complications like neuropathy or recurrent infections. It’s about 1% or 2% of all cancers, so there are 30,000 new cases in the United States with probably twice that many, 60,000-70,000 patients alive at any one time in the United States with myeloma, and there are an equal number of patients both newly diagnosed and with myeloma in Europe, as well.
Dr. Anderson: There has been an explosion of new information in multiple myeloma having to do with the genetic events that cause and are responsible for the progression of this cancer, and there is also a new appreciation of the contribution of the bone marrow micro-environment that provides a very nurturing environment and allows the myeloma cells to grow, survive, and resist drugs. Those two areas, understanding the genomic characteristics of the tumor cell and understanding those components in the patient’s bone marrow including the immune system, have allowed for us to understand much more of the pathogenesis of this disease, but importantly, have translated into precision targeted therapies that either block a pathway in myeloma cells causing growth, survival, and drug resistance, or interfere with those factors in the bone marrow microenvironment that allow the cancer cell to grow, survive, and resist drugs.
Perhaps the most exciting area outside that is in the bone marrow microenvironment for research and now clinical application are the immune possibilities to stimulate the patient’s own immune system to react against their own tumor cell in novel therapies.
Dr. Anderson: There really are standards of care in multiple myeloma. I’ll just briefly describe the progress and how we’ve gotten to where we are today in terms of the standard.
Up until about 10 or 15 years ago, patients with myeloma really had an honestly quite abbreviated response and even life span. But in the last 10-15 years, there have been wonderful advances. The classes of drugs called the immunomodulatory drugs, thalidomide, lenalidomide, and pomalidomide, the drugs called proteasome inhibitors, bortezomib, carfilzomib, and ixazomib, and most recently the monoclonal antibodies daratumumab and elotuzumab, were tested and showed efficacy in advanced myeloma in patients who literally had no other opportunities for effective treatment.
Once they demonstrated their benefit in clinical trials in advanced myeloma, they were moved into earlier stages of the disease and then combined with each other. So a standard of care that has evolved as a consequence of this are a three-drug or triplet combination, either lenalidomide, bortezomib and dexamethasone, or Cytoxan, bortezomib, dexamethasone, three drugs as a standard of care in newly-diagnosed patients with multiple myeloma.
When we see new patients with this disease we think of them as into categories. Are the patients eligible for a high-dose therapy and stem cell transplantation approach? Less than age 70 with adequate liver, lung, heart, and kidney function would make one eligible for a high-dose therapy and stem cell transplantation approach. So in such a group of patients, they would get as a standard of care three-drug, triplet initial treatment as I mentioned, either Cytoxan, bortezomib, dexamethasone or lenalidomide, bortezomib with dexamethasone. They would then get their high-dose melphalan and stem cell transplantation, and they would get maintenance therapy either with lenalidomide until progression, daily lenalidomide if they have standard risk genetically-defined myeloma, or if they have high-risk multiple myeloma, they would just change the maintenance to contain bortezomib or bortezomib and lenalidomide together. So the transplant patients are treated that way as a standard of care.
In terms of the non-transplant patients who are often more elderly, or they have a compromise in their liver, lung, heart, and kidney function, they would receive also three-drug combinations, just as I’ve mentioned, but we often lower the doses or change the schedule so it’s better tolerated and obviously they don’t receive a transplant they get continuous therapy. In the very frail patients, those who really can’t tolerate three drugs, then we do use doublets, either lenalidomide and dexamethasone most commonly, or bortezomib and dexamethasone.
So that’s the paradigm or standard of care for newly diagnosed patients; we have a whole variety of options now to treat patients should their myeloma return. So, I can mention just a couple of those. The second-generation immunomodulatory drug is called pomalidomide. The second-generation proteasome inhibitor is now carfilzomib or ixazomib. We often use triplet therapies in relapse myeloma as well, so second-generation immunomodulatory drug pomalidomide together with carfilzomib, the second-generation proteasome inhibitor, and dexamethasone, a triplet again, and those therapies, for relapse myeloma achieve very high response rates and really quite impressive durability.
And then very excitingly we have the monoclonal antibodies now, daratumumab and elotuzumab, which daratumumab in particular is exciting and active as a single agent, but either of them added to lenalidomide or to bortezomib have achieved remarkable extent and frequency of responses. So while they have been tested, that is the monoclonal antibodies, in far advanced disease, they’re now moving into the early relapse and even into the initial therapy of myeloma as we speak. So we have a standard of care. It keeps improving as we get new drugs and it’s a really most exciting time with the promise for the future even greater than what we have today.
Dr. Anderson:Gene profiling in multiple myeloma as in other cancers is very important. It will help us to understand the heterogeneity of the disease, to have new prognostic systems, and ultimately to define particular abnormalities, genetic abnormalities, that can be targeted in so-called precision therapy or novel targeted treatments. Honestly, we’re making progress in this area and what we’re learning is that it’s really quite complicated, that is the myeloma genome is complicated with many abnormalities right from the start at diagnosis, and there’s continuing, we call it DNA or gene damage concurring that underlies, and is responsible for relapse of disease.
Also, to mention for you that in myeloma this genetic heterogeneity is also manifest in multiple clones of cells. If you want multiple members of the myeloma family, 3-5 clones that are present right from the time of diagnosis, and when myeloma returns there can be several patterns of evolution. Sometimes a minor clone becomes the dominant clone, sometimes one of the early clones goes away and a new one appears, or there can be evolution, a parent clone can change over time and become the dominant clone later. So, we have a heterogeneous disease but with the current old genome sequencing and other very deep molecular and genetic profiling that is ongoing, we’re understanding the disease better than ever, and ultimately that will translate into more understanding of the different types of myeloma and better treatment for each of them.
Dr. Anderson: The excitement of the past 10-15 years has really changed the treatment paradigm and most importantly, the outcome for patients with myeloma. Patients today are living at least 3-4 times longer than they were 10 years ago, so that’s something we can all be grateful for.
I also think though that the potential for further progress in the next 5-10 years is even greater and I think the two areas to mention and highlight are those of the genomics or the understanding of the abnormalities, the circuits inside myeloma cells that are abnormal in order to develop treatments to block those circuits that allow the cell to grow, survive, or resist drugs or conversely, to understand those death circuits that should occur. Why is it these cells with all the gene damage they have, the myeloma cells, why don’t they die? So we can block their growth, but we can also turn on their death is another way. So that’s very, very exciting.
And then on the other extreme are the immune therapies, and I think they’re really exciting. If you think about it, our God-given immune systems are very selective, potent, and adaptable. If we get a cold today, it gets better. If we get the flu two weeks from now, it gets better. The immune system can just deal with threats that evolve and really in a selective way protect us. So wouldn't it be neat if we could get an immune response in patients with multiple myeloma against their own cancer? And that is a very exciting area.
In the immune area we have these immunomodulatory drugs, thalidomide, lenalidomide, pomalidomide that work by turning on the patient’s immune system. We have the monoclonal antibodies that I’ve mentioned, daratumumab and elotuzumab that are given and they label the patient’s cancer cell and allow his or her own immune system to get rid of those cells.
We have what’s called the checkpoint inhibitors. In plain English, they take the brakes off of the immune system and let the patient’s own cells react against their myeloma and reject them just as they would an infection.
We have now coming vaccines in myeloma and we have very excitingly new cellular therapies, the so-called CAR T cells, for example, where you can harvest immune cells from patients, program them to react against a target on their myeloma cells, such as something called BCMA, B Cell Maturation Antigen. But the concept is take out cells from the patient outside of the body, genetically program them to recognize this BCMA target, expand them into large numbers, and transfuse them back to the patient as his or her own immune army against their myeloma.
All of these things, these different members of the immune team are going to be combined and it’s really very impressive because the genetic complexity and continual evolution that I described just might be able to overcome, be overcome by the immune system, because the immune system is the most potent, adaptable, and selective force of all.
So, very excitingly on the genomics area, understanding the intrinsic abnormalities of the tumor cell and the immune area are honestly the most promising areas right now and almost assuredly either one of them, or maybe someday combining treatments is certain to really fast-forward progress even further.
Dr. Anderson: Personally I think it’s wonderful that there is, March is myeloma awareness and recognition month. I think that it has not always been true that there was as much attention, awareness on the part of patients, researchers, and caregivers alike on myeloma and this increased awareness and increased effort on research and translation of science to patients is the reason that we’ve had so many advances.
There are many websites. The myeloma foundations, including the International Myeloma Foundation, the Multiple Myeloma Research Foundation, the Leukemia Lymphoma Society, the American Cancer Society are among the websites I might mention as ready sources of information, up-to-date information on myeloma. I think it’s very important, and I might just mention for the patients that they’re, given the speed and the pace of the advances that I’ve mentioned, that patients now not only have their local caregivers, but they really should seek out the opinion and the guidance of, at a center of excellence in multiple myeloma.
Finally, the advances are happening quickly and the standard of care is evolving rapidly, more rapidly sometimes than certainly is going to be published in textbooks or that could be appreciated otherwise, so seeking out these websites but in particular at least visiting for a consultation a center of excellence so you can be sure that the scientific advances that we’ve mentioned really are going to be used to help you in the most effective way.
Dr. Anderson: The standard of care in multiple myeloma has markedly improved. I would just say to the hematologists and oncologists who are caring for patients with myeloma that it’s been, we’ve been remarkably privileged to watch a disease go from virtually untreatable to now a chronic disease in many patients, and I would encourage referrals to centers of excellence so that we together can carry out standard of care and advanced new clinical protocols. Already, myeloma is a chronic disease and many patients who have a normal life span and can enjoy the milestones of life with their families, but if we together carry out clinical trials of novel agents the potential for cure is very real.
Multiple Myeloma Research Foundation
Leukemia & Lymphoma Society
American Cancer Society
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