Koen van Besien, MD, PhD
With the influx of novel therapeutics and the advent of chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies, bone marrow transplant (BMT) may seem to have been put on the back burner, says Koen van Besien, MD, PhD.
Both autologous transplant and allogeneic transplant, however, are used across diseases, and each has its own set of advantages and disadvantages. These technologies currently have, and will continue to have, a role in the treatment of patients with hematologic malignancies, adds van Besien.
Van Besien, professor of medicine and director of the Stem Cell Transplant Program at Weill Cornell Medical College, and attending physician at NewYork- Presbyterian Hospital, discussed the role of BMT during a presentation at the 2018 OncLive®
State of the Science Summit™ on Hematologic Malignancies.
In an interview during the meeting, van Besien shared his insights on challenges with BMT and on the potential future for these technologies in a time when the landscape is undergoing many changes.
OncLive: Please provide an overview of your presentation.
Transplant is a technology that spans across diseases. I talked about 3 different technologies: autologous transplant, CAR T cells, and allogeneic transplant. Each of these technologies has its indications and role in the management of certain diseases.
Autologous transplantation is in the form of intensive chemotherapy supported by stem cells. It has long been established as a standard of care in both large cell lymphoma and multiple myeloma. In myeloma, there have been a lot of challenges with the role of autologous transplantation because of numerous new drugs. In the last 2 years, several studies re-established autologous transplantation as the preferred frontline treatment. It has a number of advantages, such as inducing better remissions than other treatments and more prolonged progression-free survival, and now there are also data suggesting that there is a survival advantage for patients with adverse prognostic features.
Allogeneic transplant data show that there is a steady improvement in outcomes over the last 15 years. We have addressed a number of limitations of allogeneic transplantation. We used to be limited by lack of donors, as we had match-related and match-unrelated donors available, but they were mostly for Caucasian patients, not for minorities. The technology for finding alternative donors has improved dramatically over the last 5 to 10 years, and although it is still slightly inferior, it is still a good option. I also addressed some issues of methods of preventing graft-versus-host disease (GVHD). Some quite efficient methodologies exist for preventing GVHD that do not affect relapse rates in a major way.
What are some other issues with donors?
By the time a donor is found, it may not be timely for the patient. There is often an issue of timely identification of a donor, which is particularly true for acute leukemia. Acute leukemia is an aggressive disease, and patients often have very short remissions, so it is imperative that a donor is identified in a timely fashion. Match-related donors are often siblings and they are often readily available, although one may be surprised that in our older patients, their match-related donors are not always readily available. Unrelated donors are found through a registry, and they often take months to find. Months can be too long for these patients. We then may have to resort to other donor sources to identify a donor in a timely fashion.
Can you discuss the use of transplant in acute myeloid leukemia?
We have not seen transplant complications with CPX-351 (Vyxeos). In general, as chemotherapy improves and we have more drugs that can bring patients into remission, the number of transplants will increase. The best time for a patient to undergo transplant is when they are in remission. Therefore, as we get more patients in remission, we will be able to get more patients to curative allogeneic transplant. There is always a concern that the preceding chemotherapy may set the patient up for toxicities, but we have not seen that yet with CPX-351.
What role do you envision BMT having across hematologic malignancies with the addition of many novel regimens?
The role of autologous transplantation is there and will continue to be there for a long period of time. A lot of novel therapies require infinite treatment, which is quite cumbersome. It is often not apparent from the formal phase III study, but tolerance and compliance with long-term exposure to these novel, supposedly nontoxic, chemotherapies are quite a challenge. Autologous transplantation is quite arduous for the patient, but it stretches over a limited period of time, which has its advantages. Patients can recover and be without treatment for a prolonged amount of time.
The other argument is economic. We used to think of autologous transplantation as a very expensive treatment. Now, with numerous new expensive drugs, it may as well turn out that autologous transplantation is the [least expensive] treatment.
Allogeneic transplantation will continue to be used, particularly in acute leukemia, but also in subsets of patients with lymphoma and multiple myeloma.
Can you highlight some of the points from the case study that you presented?
I briefly presented a case of a patient with large cell lymphoma who was treated on the JULIET trial of CAR T cells. This patient had very refractory disease and had no other options. What I illustrated was how we address the challenge of maintaining the health of a patient with aggressive large cell lymphoma until the CAR T cells are ready for infusion. I also illustrated the serious toxicity that can occur with CAR T-cell therapy. The anti-CD19 products, in particular, can cause cytokine release syndrome, but that fortunately did not occur in this patient.