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The state of the science: Starting a dialogue about HSCT
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In 2013, Science magazine designated cancer immunotherapy as its breakthrough of the year.
Excitement in this field has been building for years, from the development of cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors and anti-PD–1 antibodies to the emergence of chimeric antigen receptor (CAR) T cells as a viable therapeutic option for the treatment of high-risk hematologic malignancies.
In the past year, additional exciting data emerged to demonstrate that the immunotherapy movement was gaining significant momentum. A paper published in The New England Journal of Medicine in July showed that the combination of ipilimumab (Yervoy, Bristol-Myers Squibb) and anti-PD–1 produced rapid and deep responses in a substantial number of patients with melanoma. The ASH Annual Meeting in December featured striking results from CAR T-cell therapy, including clinically significant effects in chemotherapy-refractory diffuse large B-cell lymphoma.
William Wood
Besides the exciting empiric data that are being generated, cancer immunotherapy also holds broad conceptual appeal. There is a suggestion now that common platforms might target a wide variety of malignancies that have vast molecular heterogeneity. Although this notion of universality in anticancer treatment was once unrealistic, increasingly there is hope that common, shared approaches to anticancer treatment might eventually become feasible.
Evolution of HSCT
Against this background, it is worth remembering that we currently have available a standard-of-care approach that incorporates a shared platform and harnesses the power of immune-based therapy to treat high-risk diseases. Indeed, the use of hematopoietic stem cell transplantation continues to grow each year in the United States and around the world.
In parallel with advances in other cancer treatments, HSCT has evolved rapidly in the past 2 decades in ways that may be unfamiliar to those who learned about transplant earlier in their careers. Many complications that were fairly common in earlier years, such as Pneumocystis jiroveci pneumonia and cytomegalovirus infection, are less common in the modern era with effective prophylactic and pre-emptive strategies.
Thanks to the advent of reduced-intensity conditioning regimens and improvements in supportive care, we now have the ability to safely perform transplantations for older patients and those with comorbid illnesses. In some centers, it is not uncommon to perform autologous or even allogeneic stem cell transplants in patients as old as age 75 years.
Long-term studies suggest that average health-related quality of life and functional status among survivors — including older patients — recover within a year to pre-transplant levels. Data continue to emerge regarding the feasibility of alternative donor transplantation with haploidentical or umbilical cord blood transplants, meaning that soon we should be able to readily identify an available donor for anyone who would be a suitable candidate for an allogeneic stem cell transplant.
Nevertheless, continued underutilization of transplantation in patients who might otherwise benefit suggests that many of the improvements in the field may not be well known among referring providers.
A dialogue begins
In light of these observations, I would like to devote several columns in the next year and beyond to starting a conversation about HSCT with the HemOnc Today readership. This seems an opportune time to begin this dialogue, as the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) — a large transplant cooperative group chartered by the NHLBI and NCI — recently completed a State of the Science Symposium (SOSS) in February coincident with the annual national meetings of the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
For those who are unfamiliar, the BMT CTN SOSS is a remarkable gathering of the scientific and clinical leaders in HSCT to discuss high-priority areas of study in the years ahead. The BMT CTN has had three of these symposia, with the others occurring in 2001 and 2007. These symposia have been highly successful and have led directly to the development and execution of large phase 2 and phase 3 studies that address critical questions in the field.
For example, the 2007 symposium identified as a priority the development of a phase 2 trial of calcineurin-free regimens in patients with high-risk chronic graft-versus-host disease. Subsequently, a phase 2/phase 3 study was developed and conducted to compare sirolimus plus prednisone with sirolimus plus calcineurin inhibitor plus prednisone.
A phase 3 comparison of full-intensity conditioning vs. reduced-intensity conditioning in allogeneic transplant recipients aged 30 to 60 years with acute myeloid leukemia was deemed a high priority. A 356-patient, randomized study was subsequently initiated, and accrual is ahead of schedule.
Also, the 2007 symposium identified as a high priority a phase 3 comparison of peri-transplant stress management interventions on quality of life. Subsequently, a study of exercise and stress management in 711 patients undergoing transplantation was designed and completed, with results presented at ASH in 2013 and currently in press in manuscript form. At the 2014 BMT CTN SOSS, 12 study concepts from 10 topic-specific committees of experts were prioritized for subsequent development.
As these studies represent both the contemporary state-of-the-art and future of HSCT, I will plan to spend one upcoming monthly column per committee highlighting that group’s prioritized concepts.
To introduce each column, I will start with one or more hypothetical clinical vignettes to contextualize the problems being addressed. I will then review the committee’s suggested strategy, as well as the background data that support each concept.
My hope is that these columns will lead to discussions among the HemOnc Today readership about the field of transplant and stimulate several readers to write to me directly with thoughts and questions about these topics or about transplant in general. We can continue these conversations online at www.Healio.com/HemOnc, and I also will address them in written form as I write subsequent columns.
All comments are welcome, so please email me anytime at wawood@med.unc.edu. Hopefully I can help to disseminate knowledge, dispel myths and promote the continued use of autologous and allogeneic HSCT for appropriate patients who might benefit from it.
References:
Couzin-Frankel J. Science. 2013;342:1432-1433.
Ferrara J. Biol Blood Marrow Transplant. 2014;20:149-153.
Kochenderfer JN. Blood. 2013;122:4129-4139.
For more information:
William Wood, MD, is an assistant professor of medicine in the division of hematology/oncology at the University of North Carolina in Chapel Hill. He also is a HemOnc Today Editorial Board member. He can be reached at UNC Health Care System, Division of Hematology and Oncology, 101 Manning Drive, Chapel Hill, NC 27514; email: wawood@med.unc.edu. You also may follow him on Twitter (@WoodBD).
Disclosure: Wood reports no relevant financial disclosures.