While hematopoietic stem cell transplant (HSCT) offers a curative treatment option for many patients, oncologists face unique challenges, including the underutilization of transplant, the need for improved communication between the transplant center and the community oncologist, and the implementation of CAR T-cell therapy. In this interview with i3 Health, Miguel-Angel Perales, MD, addresses these challenges and discusses the importance of clinical trial enrollment and innovative programs that make trials more accessible to patients.
What are the most challenging aspects of managing HSCT patients?
Miguel-Angel Perales, MD: One of the first challenges we deal with in the management of a transplant patient is referral to transplant. The National Marrow Donor Program has put together data where they look at the incidence of cancer in the population, and then they look at the number of transplants that are being performed in that area. Currently, many patients are not being referred to transplant.
New York is a prime example of that. There's definitely an underutilization of transplant for patients. That's true for both autologous transplant for patients with myeloma as well as allogeneic transplant for patients with acute leukemia.
We need to make an effort to educate oncologists treating these patients that transplant provides a curative option for many of these patients and that they should be referred early rather than late, where the results are not as good.
What are some of the best practices that you recommend to community oncologists who are managing HSCT patients?
Dr. Perales: I would distinguish between centers that are performing the transplants and community oncologists who are probably not performing the transplant. In centers that perform transplants, the standards are usually well established, and the expectation is that the transplant center is FACT accredited. You have standard guidelines for the management of patients. That data is reported to the CIBMTR, which is the national registry that collects the data under federal mandate. The CIBMTR gives an annual report card to centers where you see the expected survival and the actual one-year survival. That metric allows you to judge the quality of a center. Are they doing as well as they should? Are they doing better? Are they not doing as well? Insurance companies look at that data very closely and sometimes take action on that.
When you think about the community oncologists, they may be taking care of transplant patients who've gone to a referral center and then come back after transplant. The management of a patient who had an autologous transplant is relatively straightforward because once the patients are beyond 100 days and have recovered, management is not much different from a standard oncology patient. The patients undergoing allogeneic transplant have more long-term issues, like management of immune suppression drugs, monitoring for potential risk of infections, monitoring for graft-versus-host disease (GVHD), and so forth.
The key is to have good communication with the transplant center. In places where there is enough of a critical mass, the question is whether it would be better to have one oncologist deal with all the patients who return for transplant rather than have five or six oncologists in the same practice, each seeing two or three patients. You can develop a nucleus of expertise, or maybe even have an advanced practice provider who develops that level of expertise, for example in GVHD and some of the other complications of allogeneic transplant, who can really provide comprehensive care to the patients.
What questions do you commonly encounter from patients and caregivers about the treatment, and how do you counsel them?
Dr. Perales: That is a big question. We get a lot of questions from the patients and caregivers. Common questions that come up are: What's the likelihood of a cure? What is the risk of dying?
While allogeneic transplant is a potential cure for many of these diseases, it can also have a risk of non-relapse mortality. That can be anywhere from 10-20%, and sometimes 30-40%, particularly in patients who are more frail or have more advanced disease. In that case, you want to balance the benefit and the risk of the transplant. In some patients, the benefits don't justify the risks. In these cases, we will not recommend a transplant.
People want to have a general sense of the outcomes. Patients are also focused on quality of life, and not necessarily quantity of life. That is also a part of the discussion. Regarding allogeneic transplant, one of the main complications is GVHD, particularly chronic GVHD which can have long-term impact on quality of life, and the patients want to understand what that means.
When you're doing the pre-transplant consultation and the patients are faced with what is typically a fatal disease, the conversation is very focused on being alive. Once they've made it through to post-transplant, if they have complications then the focus is the impact of the complications. Will they resolve? What is the expectation of resolution? What long-term complications will I have to live with? When can I get back to a normal life? When can I get back to work? When can I travel? When can I go back to restaurants? So, sometimes the questions are about very practical things.
I was in a clinic recently and was asked: Can I drink well water again? Can I go swim in the ocean? When can I garden? Because of the risk of infections, there are a lot of restrictions around all these activities.
What are some of the promising advances that you expect to see with transplant in the near future?
Dr. Perales: Overall, the outcomes of transplant have improved dramatically over the last two decades. It's a combination of a better understanding of the biology of transplant, a better selection of donors, improvement in the technology that allows us to better match donors, improvement in our approach to prevent GVHD, and a lot of improvement in supportive care. That has led to significant improvements in survival in adult and pediatric patients.
The other aspect is the integration of post-transplant maintenance therapy. We now have access to targeted drugs that we can give to certain patients that reduce the risk of relapse after transplant, and therefore increase the chance of cure. There is also a developing area of cell therapy, chimeric antigen receptor (CAR) T cells, now approved for acute leukemia and lymphoma. We're probably going to see an approval for myeloma as well next year.
CAR T cells and transplants live side by side and which therapy we recommend versus the other is an evolving field. As a transplant physician, I'm comfortable delivering either transplant or CAR T cells. We just have to decide for each individual patient when it's more appropriate to offer either a transplant or CAR T cells. That's something that is evolving based on new data that's coming out.
What role do you feel like clinical trials are going to play when it comes to HSCT patients?
Dr. Perales: Just like anything in oncology, most of our advances have been based on clinical trials. It's critical to encourage accrual to clinical trials. If you look at pediatricians, they do a much better job of putting children in clinical trials for oncology, whereas, in adults, the national average is less than 10%. That's very unfortunate. We really want to try and improve on that. The trials can be looking at questions of supportive care, conditioning regimen, prevention of GVHD, or post-transplant maintenance. There are many different questions we can ask. In some patients, we can ask more than one question. Ultimately, progress is going to come from clinical trials.
Why do you think there's that big difference between pediatric and adults as far as the clinical trials?
Dr. Perales: The pediatric oncology population is much smaller and most of them are treated at large referral centers, whereas most adult patients are treated in the community; so the community oncologist does not have the resources or time for it and doesn't have the research infrastructure to put somebody in a trial.
One of the efforts that MSKCC is leading is to build a network of sites near us where the clinical trials are offered, so that patients who live in Nassau County for example can go on a clinical trial without having to trek into the city. Rather than force a patient to commute two hours to get on a clinical trial, we're trying to bring the trial to the patients.
You can imagine a 70-year-old who is 2-3 hours away from a big cancer center is not going to uproot his/her whole life to go on a clinical trial, and the local doctor is not going to offer it; whereas, if we can bring the trial to the local doctor and then to the local patient, then hopefully it will increase the accrual.
About Dr. Perales:
Miguel-Angel Perales, MD, is the Deputy Chief of the Adult Bone Marrow Transplantation Service and Director of the Adult Bone Marrow Transplantation Fellowship Program at Memorial Sloan Kettering Cancer Center. He is also an Associate Professor at Weill Cornell Medical College. Dr. Perales has co-authored more than 130 peer-reviewed publications in academic journals. His research on improving outcomes in stem cell transplantation focuses on finding ways to reduce the risk of complications, relapse, and GVHD. He is currently leading a clinical trial to determine the safest way to perform a transplant using donor stem cells in patients with relapsed Hodgkin lymphoma. His additional areas of research include CAR T-cell therapy and the use of agents such as interleukin-7 and KGF to enhance post-transplant immune reconstitution.