Summary
A significant portion of patients with diffuse large B-cell lymphoma (DLBCL) had durable responses after allogeneic stem cell transplant (alloHCT), despite high rates of graft-versus-host disease (GVHD) and wide-ranging disease status, according to work presented at the 2020 ASCO Annual Meeting.
As novel therapies such as CAR-T continue to progress, there is increased scrutiny on the long-term outcomes of alloHCT in patients with DLBCL.
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Original Article
Promising Responses of Allogeneic Stem Cell Transplantation for DLBCL
Oncology Times
By Dibash Kumar, Das, PhD
A significant portion of patients with diffuse large B-cell lymphoma (DLBCL) had durable responses after allogeneic stem cell transplant (alloHCT), despite high rates of graft-versus-host disease (GVHD) and wide-ranging disease status, according to work presented at the 2020 ASCO Annual Meeting.
As novel therapies such as CAR-T continue to progress, there is increased scrutiny on the long-term outcomes of alloHCT in patients with DLBCL.
In this study, Puliafito and colleagues investigated the characteristics and long-term follow-up of patients with DLBCL who underwent alloHCT at a single institution between 2008 and 2018 (Abstract E19524). In total, 18 patients were included and their disease, transplant and GVHD history were retrospectively collected from reports to chart review and CIBMTR. Analysis included outcomes of progression-free survival (PFS) and overall survival (OS).
The 18 patients had a median age of 53 years old (range 30-67 years) and were 19.5 months post-diagnosis (range, 6-83 months) at transplant. The median Karnofksy score was 70, and the 78% of the patients had stage IV disease. The median number of previous chemotherapy regimens was 3. DLBCL was chemosensitive, chemoresistant and undetermined in 61%, 22%, and 16% of the patients, respectively. The majority of the conditioning regimens were Flu/Mel (n=10), but also included Flu/Mel/ATG, Flu/TBI, Flu/Cy/TBi, Cy/TBI, and BEAM. Acute GVHD developed in 89%, despite 94% of patients receiving GVHD prophylaxis; chronic GVHD developed in 28% of patients. PFS rates were 56%, 33%, and 24% at 6 months, 1 year and 3 years, respectively. In the same time interval, OS rates were 72%, 39% and 24%. The median time to death was 7.5 months (range, 1–74; mean 12.9 months) with primary disease as the most common cause of death in 28% of the patients. Twenty-two percent of patients were alive with a maximum survival of 58 months.
Oncology Times spoke to Benjamin Puliafito, MD, Internal Medicine Resident at the Mount Sinai Hospital and lead author of the study to discuss several aspects of their work.
What was the rational for this study?
Puliafito: Our study was part of a quality initiative to assess our institution's outcomes with allogeneic HCT for diffuse large B-cell lymphoma patients over the past 10 years. We wanted to look at benchmark outcomes with a plan to compare them with CIBMTR data and other single-center studies. Our study was prompted by the emerging role of CAR-T therapy and the question of whether allogeneic transplant could still have a potential role in our patients with diffuse large B-cell lymphoma patients.
Is this study population representative of the real-world population of people who have DLBCL? Can you share some details on the demographics?
Puliafito: Our patient demographics appear to be representative of the general DLBCL patient population. The majority of our patients (72%) were white or Caucasian with a male predominance (61%), similar to CIBMTR studies on alloHCT in DLBCL. The median age at the time of diagnosis was 49 years old, which is younger than many DLBCL patients but consistent with the fact that younger patients were more likely to go on to alloHCT.
The application of alloHCT has been historically limited to healthier, younger patients given the high rates of non-relapse mortality associated with this procedure. Do the current study results give you confidence to use this procedure in broader range of patients? In which candidates/situations should this treatment process be considered?
Puliafito: One of the most important findings is that the patients who underwent alloHCT at our institution over the past 10 years had a broad range of characteristics. The median age of the patients undergoing alloHCT was 53 years old, ranging from 30 to 67 years old. The median Karnofsky performance status of 70. Only 60% of the patients had had a prior autologous HCT (autoHCT) and almost a quarter of the patients had chemoresistant disease. This range of patient factors and disease status is clearly an important context for our overall outcomes. This broad range of patient characteristics reflects how the application of alloHCT has narrowed over the past 10 years. Overall, we foresee the paradigm shifting for alloHCT only to be considered in relapsed disease after CAR-T therapy.
What are some limitations of the study?
Puliafito: The biggest limitation of our study is that it is retrospective in design. Moreover, given the relatively small number of patients in the study, we are unable to determine the patient or disease factors that may have improved response or survival in alloHCT. Importantly, new therapies including CAR-T have evolved over the past decade and become standard of care. The future patient population of allogeneic transplant candidates in DLBCL will have received CAR-T and/or other therapies, and it remains to be seen how such prior immunotherapies will have an effect on allogeneic stem cells.
Dibash Kumar, Das, PhD is a contributing writer.