Outpatient Transplant and CAR T-Cell Therapy: A Paradigm Shift in Care Delivery

The traditional model of inpatient care for transplant and cellular therapy has long been associated with extended hospital stays, explained Othman Salim Akhtar, MD, an assistant professor in the division of hematology and oncology at the Medical College of Wisconsin (MCW). While extended hospital stays can be necessary for close monitoring, prolonged stays are often accompanied by declines in physical function, quality of life, and significant psychological impact.¹

During a presentation at the American Society for Transplantation and Cellular Therapy (ASTCT) 4th International Conference on Toxicities of Transplantation and Cellular Therapy, Akhtar explained that the isolation and restricted mobility of hospitalization have been likened to the effects of zero-gravity conditions experienced by astronauts during orbit, which has been known to lead to anxiety, depression, mood swings, irritability, and fatigue. During extended hospital stays, patients may experience sleep disorders, delirium, severe anxiety, depression, and even symptoms of post-traumatic stress disorder (PTSD).¹

“The isolation and the bedrest that you see in these patients is very similar to being in a zero-gravity situation,” Akhtar said during the ASTCT presentation in Philadelphia. “If you look at the psychological impact, this is not just during the hospitalization where patients can have delirium and anxiety and depression, but even after discharge around 20% to 30% of patients will actually report symptoms of PTSD.”¹

According to Akhtar, the known impact of extended hospital stays helps to clarify the need to explore outpatient care models as a viable alternative, with an aim of reducing hospital stays while maintaining—or even improving—patient outcomes.¹

Outpatient Models of Care

There are 3 primary models for the delivery of outpatient transplant and cellular therapy. Image Credit: © nameera_juwairiya - stock.adobe.com

Akhtar explained that there are 3 primary models for the delivery of outpatient transplant and cellular therapy, each tailored to patient needs and institutional capabilities¹:

1. Total Outpatient Model: Conditioning and infusion are managed outpatient, and patients are only admitted inpatient if complications arise.
2. Outpatient/Inpatient: Conditioning and infusion are outpatient, followed by planned inpatient monitoring for potential complications.
3. Early discharge: Conditioning and infusion are inpatient, with patients discharged early.

Regardless of the model, Akhtar noted that certain critical infrastructure elements are required to make these programs successful.¹

“Number 1, you need to have a very robust outpatient clinic where patients can be seen for planned visits and to address complications. As my boss told me the first day I joined, ‘If ER is your best bet, the program is going to fail.’ You need to have an outpatient clinic that is hospital-based so you can see these patients, a robust 24-hour triage line, and you have to have the ability to rapidly admit these patients,” Akhtar said. “As far as the supportive care and [infectious disease] approach is concerned, these vary from institution to institution, but tend to be a little more aggressive in the outpatient setting compared to the inpatient setting.”¹

Evidence Supporting Outpatient Models

The bulk of data available that supports how outpatient transplant works is in multiple myeloma (MM), according to Akhtar.¹ In one study published in 2017 in the European Journal of Haematology that was conducted at MD Anderson, investigators assessed the safety of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autoHCT) for patients with MM in the outpatient setting.^1,2 In the study, 1046 patients (669 inpatient, 377 outpatient) were included, with patients in the outpatient setting trending younger (58 [34-78] vs 62 [31-82], P < .001) and more likely to have an hematopoietic stem cell comorbidity index (HCT-CI) score of less than 2 (P = .003) and creatinine of less than 2 (P < .001).^1,2

The investigators observed no differences in treatment-related mortality between the inpatient and outpatient cohorts, but the inpatient group experienced significantly more grade II to V (P = .003) and grade III to V (P = .003) adverse events (AEs).^1,2 Additionally, 2 year progression-free survival (PFS) was significantly longer in the outpatient group (60% vs 50%, HR =HR 0.7, 95% CI 0.6-0.9, P = .005), as was 2-year OS (83% vs 77%, HR 0.6, 95% CI 04-0.9, P = .01).² Shah et al noted that although the data show outpatient autoHCT can be safely performed for certain patients with MM, the differences in outcomes in each setting are likely related to baseline clinical characteristics.^1,2

In a study conducted at MCW that was published in Bone Marrow Transplant in 2015, Graff et al compared the outcome of 230 patients with MM or lymphoma who underwent autoHCT on an inpatient vs outpatient basis within a single transplant program.^1,3 In the study, hematopoietic recovery occurred earlier in the outpatient cohort, with median time to neutrophil recovery at 10 vs 11 days (P < .001) and median time to platelet recovery at 19 vs 20 days (P = .053).^1,3 In the outpatient cohort, 51% never required admission, with this percentage increasing in later years. Grade III to IV non-hematologic AEs occurred in 29% of both cohorts. In the outpatient cohort, non-relapse mortality was 0% at 1 year, and in the inpatient cohort it was 1.5% (P = .327).^1,3 Two-year PFS was 62% for outpatient vs 54% for inpatient (P = .155), with 1- and 2-year OS at 97% and 83% for outpatient, respectively, and 91% and 80% for inpatient, respectively (P = .271).^1,3

Graff et al concluded that, with daily outpatient evaluation and aggressive supportive care, outpatient autoHCT can result in excellent outcomes for patients with MM and lymphoma.^1,3

According to Akhtar, there are other studies, some of which are more recent, that have also demonstrated the safety and feasibility of outpatient autoHCT in both the total outpatient and hybrid models. Two studies demonstrating feasibility in the total outpatient model include a study written by Larsen et al (2022) focusing on MM,^1,4 and one written by Cavalier et al (2020), focusing on non-Hodgkin lymphoma (NHL).^1,5 A study showing the feasibility of a hybrid model approach is Reid et al (2016), focusing on NHL.^1,6

“What these studies are telling us, essentially, is that outpatient transplant care models are feasible. They do not compromise the safety and efficacy of care delivery in carefully selected patients, even though between a third to half of patients end up getting admitted, the lengths of stay are significantly reduced,” Akhtar said. “It's also important to recognize that certain host factors are predictive for unplanned admissions… so multidisciplinary care is so important.”¹

Quality of Life and Economic Considerations

The impact of outpatient models on patient quality of life has shown mixed results. Studies indicate that global quality of life measures may not differ significantly between inpatient and outpatient care, as chemotherapy-related AEs tend to be more present. However, outpatient care is associated with better social and familial well-being, as patients can spend more time in familiar environments.¹

On the downside, outpatient care often shifts financial burdens onto patients and caregivers, Akhtar explained. Transportation costs, caregiver time off work, and other indirect expenses can create barriers, particularly for patients without strong support systems. Caregiver apprehension is another challenge, as families may feel overwhelmed by the responsibility of managing complex medical care at home.¹

CAR T-Cell Therapy in Outpatient Settings

CAR T-cell therapy presents unique challenges compared to transplants, given the high incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).¹ According to Akhtar, institutions such as Mayo Clinic and MCW have pioneered outpatient CAR T programs with varying approaches¹:

• Remote Monitoring: Mayo Clinic utilizes technology integrated with electronic medical records to provide continuous monitoring and alerts. Despite these advancements, only 16% of patients in one cohort completed therapy without requiring admission.
• Hospital-Based Outpatient Management: MCW manages CRS and ICANS with protocols allowing for outpatient administration of tocilizumab (Actemra; Genentech) and dexamethasone. However, approximately 70% of patients ultimately require admission, particularly for more severe cases.

Studies exploring prophylactic measures, such as early tocilizumab or dexamethasone administration, have shown mixed results. While these interventions may mitigate certain AEs, they do not universally prevent admissions or complications, which emphasizes the need for individualized care plans.¹

Balancing Benefits and Challenges

Outpatient transplant and CAR T models offer compelling benefits, including reduced inpatient length of stay, cost savings for health care systems, and improved social aspects of quality of life. However, these benefits must be weighed against potential challenges, such as caregiver burden and equity concerns. To help with address these challenges, it may be beneficial to ensure caregivers are adequately supported and trained, which can mitigate some of the stress associated with outpatient care. Additionally, to address equity concerns, institutions may want to explore strategies to reduce financial barriers, such as transportation subsidies or caregiver support programs, which may make outpatient care more accessible to a broader patient population.¹

Conclusion

Outpatient care models for transplant and CAR T-cell therapy represent a significant evolution in oncology and hematology practice. While these models demand robust infrastructure and careful patient selection, they offer a safe, feasible alternative to traditional inpatient care. By reducing hospital stays, outpatient models can address some of the physical and psychological burdens of extended hospitalization, while also aligning with patient preferences for home-based recovery. As the field advances, continued research and innovation will be critical to optimizing these models, addressing caregiver and economic challenges, and ensuring equitable access for patients.

REFERENCES

1. Akhtar OS. Unique Considerations for the Outpatient HCT and Cellular Therapy Setting. Presented at: ASTCT 4th International Conference on Toxicities of Transplantation and Cellular Therapy; Philadelphia, PA; November 15-16, 2024.

2. Shah N, Cornelison AM, Saliba R, et al. Inpatient vs outpatient autologous hematopoietic stem cell transplantation for multiple myeloma. Eur J Haematol. 2017;99(6):532-535. doi:10.1111/ejh.12970

3. Graff TM, Singavi AK, Schmidt W, et al. Safety of outpatient autologous hematopoietic cell transplantation for multiple myeloma and lymphoma. Bone Marrow Transplant. 2015;50(7):947-953. doi:10.1038/bmt.2015.46

4. Larsen K, Spencer H, Mohan M, et al. Feasibility of Outpatient Stem Cell Transplantation in Multiple Myeloma and Risk Factors Predictive of Hospital Admission. J Clin Med. 2022;11(6):1640. doi:10.3390/jcm11061640

5. Cavalier K, Cazeau N, Bhatt V, et al. Feasibility of and Decreased Inpatient Hospital Days for Non-Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL) Patients with Outpatient BEAM Using Daily Etoposide and Cytarabine and Autologous Hematopoietic Stem Cell Transplantation (AHCT). Transplantation and Cellular Therapy. 2020;26(suppl 3).

6. Reid RM, Baran A, Friedberg JW, et al. Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for lymphoma is safe, feasible, and cost-effective. Cancer Med. 2016;5(11):3059-3067. doi:10.1002/cam4.879