Trends in Stem Cell Transplantation Refusal for Myeloma Treatment – Targeted Oncology

Determining the right path for multiple myeloma treatment is often complex as various decisions can significantly impact patient outcomes. Among these decisions, the consideration of autologous hematopoietic stem cell transplantation (HSCT) stands as a cornerstone, offering hope for improved progression-free and overall survival. However, recent research from Chakra Chaulagain, MD, showed that a small yet significant percentage of patients are refusing this potentially life-saving procedure.

An analysis of National Cancer Database (NCDB) data presented at the 2023 American Society of Hematology Annual Meeting showed that of 43,653 patients with newly diagnosed multiple myeloma recommended for HSCT, 98.05% proceeded with the procedure. However, the remaining 2% opted out. Some of the key factors influencing the patient's decision regarding HSCT related to socioeconomic, racial, and geographic disparities.

According to Chaulagain, director of the multiple myeloma and amyloidosis program at Cleveland Clinic Florida, older patients with multiple myeloma, those with comorbidities, and those lacking robust insurance coverage are more likely to decline HSCT. Furthermore, Black patients exhibited higher rates of refusal compared with White patients (OR, 1.38; P =.0022).

These findings underscore the need for future studies and policy changes to address socioeconomic and racial disparities in access to transplantation.

In an interview with Targeted OncologyTM, Chaulagain discussed the trends of rates of autologous HSCT refusal among patients with multiple myeloma.

Targeted Oncology: What led to your research on autologous HSCT refusal rates among patients with multiple myeloma?

Chaulagain: There is minimal data on real-world findings about refusal of a standard-of-care, for example, stem cell transplantation in [patients with] multiple myeloma. We wanted to explore some ideas about what are the factors that are contributing to the refusal transplant, which is the current standard-of-care, and it is known to improve both progression-free and overall survival based on randomized clinical trials. But there is limited real-world data around this subject, so we decided to investigate the NCDB.

Tumor microenvironment background with cancer cells, T-Cells, nanoparticles, molecules, and blood vessels. Oncology research concept: ratatosk - stock.adobe.com

What were the methods and design of this analysis?

This is a retrospective analysis of a very large number of [patients with] multiple myeloma that were treated by a commission of cancer-accredited cancer centers throughout the United States. There are at least 1500 of these types of cancer centers, and they report to this NCDB, where they have all of this data collected. NCDB captures about 70% of all cancer cases in the United States. We decided to get those data and analyze them just for multiple myeloma with the purpose of finding what are the variables and clinical factors that are responsible for refusal of autologous stem cell transplantation in [patients with] myeloma.

What were the key findings regarding the utilization of autologous HSCT in patients with multiple myeloma?

We had 43,600 patients [with] newly diagnosed multiple myeloma, and they were recommended to undergo a stem cell transplantation after completing their initial induction therapy by their doctors. Ninety-eight percent of the patients did go and do the stem cell transplantation, but 2% refused. We analyzed the various socioeconomic, racial, ethnic, and geographic factors about what made them refuse the stem cell transplantation.

Did the study identify any patient subgroups who were more likely to refuse?

We did find that older patients had a higher odds of refusing essential transplantation. Male [patients] had higher odds of accepting transplantation and females had higher odds of refusing it. Patients with more major medical comorbidities had higher odds of refusing it. Patients without insurance, or Medicare and Medicaid, had higher odds of refusing stem cell transplantation compared with patients who had private insurance. Median household income was also a significant predictor of whether the patient will go for a stem cell transplant or not. Those who were earning less than $63,000 annually had a higher odds of refusing autologous stem cell transplantation. Black patients, for example, had a higher odds of refusing transplantation, and Hispanic [patients] had a lower odds of refusing transplantation.

Were there any significant trends in the refusal rates over this time period?

The study time point was from 2004 until 2020. Patients who were diagnosed and treated closer to 2020 had a higher odds of refusing transplantation, and patients who were diagnosed closer to 2004 had a higher odds of accepting transplantation or lower odds of refusing transplantation, and we think it may have to do with advancement in novel therapies, particularly monoclonal antibody therapies in multiple myeloma in the current years.

What are the potential reasons as to why patients refused more than others?

The higher age, decreased income, not having strong private insurance, and also, the facility type did matter. For example, patients who were treated at nonacademic facilities had a higher odds of refusing transplant compared with patients that were treated at academic centers. There was also regional variation on whether the patient would refuse or accept transplant. For example, in South Atlantic states in the United States, patients had higher odds of refusing transplantation.

What are the implications of these findings?

We found that there was significant variation across the United States in terms of racial, economic, and geographic variation, and this data can and should be used for designing future clinical studies in a prospective basis.

How have recent advancements in the multiple myeloma space such as the emergence of novel therapies impacted transplantation?

Based on our studies, the emergence of novel therapies and immunotherapy, particularly anti-CD38 monoclonal antibodies like daratumumab [Darzalex], have led to decrease utilization of transplant, and it will probably further evolve down the road because of the availability of even more effective novel therapies such as [chimeric antigen receptor] T-cell therapy, and bispecific T-cell engager therapy. The role of transplant will continue to evolve and will probably continue to diminish down the road.

What barriers still need to be addressed regarding transplant?

These are bigger decisions at the policy and procedure and legislation [levels], like increasing incidence coverage, increasing socioeconomic aspects for all of our patients, particularly those who are marginalized or who are minorities. This is a bigger, national goal and the legislator has to act on it,

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Trends in Stem Cell Transplantation Refusal for Myeloma Treatment - Targeted Oncology

Cell therapy for retinal degenerative disorders: a systematic review and three-level meta-analysis – Journal of … – Journal of Translational…

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Japanese hospital to evaluate technology used in European trials – Labmate Online

Leading stem cell researchers at Shonan Kamakura General Hospital (SKGH), Japan, are collaborating with regenerative cell therapy developer CellProthera to manufacture autologous endothelial progenitor cells (EPCs) for use in forthcoming clinical trials. Led by world-renowned stem cell expert Takayuki Asahara, MD, PhD, the SKGH research team will use the companys automated manufacturing technology, along with single-use cell culture kits to produce therapies for patients with ischemic and renal diseases.

Professor Asahara, Deputy Director of Shonan Research Institute of Innovative Medicine atSKGH, was the first researcher to isolate EPCs from peripheral blood. EPCs are naturally deployed in the body to repair blood flow after it is restricted (as in ischemic stroke).

CellProtheras StemXpand, which has been in use in European trials to grow patients own cells into a therapeutic dose, will be rigorously tested to meet SKGHs manufacturing specifications and adapted as needed to begin qualification runs for an upcoming clinical trial. After the collaborators confirm consistency and reproducibility both in the manufacturing process and with the previously manufactured product, Prof. Asaharas team will perform validation runs to ready the technologys use for clinical testing.

We are honoured to work with Prof. Asahara given his ground-breaking experience in the regenerative medicine space and think he is the ideal partner to demonstrate the utility of our manufacturing technology beyond our own pipeline, said Matthieu de Kalbermatten, CEO, CellProthera. As a long-time advocate for the use of stem cells for the treatment of ischemic and renal diseases, I am hopeful this collaboration will pave the way for the StemXpand and StemPack to play a pivotal role in the research and development of stem cell treatments across the globe.

Ischemic diseases remain one of the leading causes of death in Japan, with limited treatment options, commented Prof. Asahara. We hand-picked CellProthera for collaboration based in part on how StemXpand, a tried and trusted technology, will help us meet the needs of patients with ischemic diseases through our development of targeted stem cell therapies.

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Japanese hospital to evaluate technology used in European trials - Labmate Online