The patient and caregiver experience of CAR T-cell therapy: A qualitative analysis

Abstract

Background/purpose.

Immunotherapies, such as CAR-T, have revolutionized cancer treatment for some cancers. However, these treatments often require active participation of a family member or friend to act as a caregiver at home for several weeks after infusion. Given the novelty of CAR-T, there is a need to better understand the experience of patients receiving these treatments and their caregivers.

Methods.

As part of a larger study, patients receiving CAR-T and their caregivers were recruited to participate in semi-structured interviews about their experiences in treatment within a week of hospital discharge. Guided by the Dyadic Cancer Outcomes framework and using an inductive approach, trained coders qualitatively analyzed interview transcripts to identify key themes.

Results.

Ten patients and nine of their caregivers participated in interviews in 2021. Three key themes surrounding CAR-T experiences were identified: individual, relational, and contextual. Firstly, the CAR-T experience impacted physical and psychosocial aspects of life for patients and caregivers. Secondly, the isolating and intensive nature of caregiving after discharge affected relationships between patients and caregivers. Thirdly, social contexts such as food, housing, and travel costs complicated the treatment experience.

Conclusions.

Although CAR-T is a novel treatment, the experiences of patients and especially caregivers are often similar to those receiving other forms of cancer treatment. However, due to the requirement of a constantly-present caregiver in the weeks after therapy, these experiences may have been intensified. Future work is needed to develop inclusive, family-centered programs to help support patients and their caregivers through cancer treatments.

Introduction

Cellular immunotherapy, including chimeric antigen receptor (CAR) T cell therapy, has revolutionized cancer care.[1, 2] However, severe-life threatening toxicities and other side effects can also be associated with these treatments.[3] For this reason, patients are generally managed on an inpatient basis for 1-2 weeks post-infusion. They then transition to informal caregivers for monitoring—often by family or friends--in a local outpatient setting for 30 days post-infusion to quickly reach medical professionals in case of an adverse event.

Prior research[4] has demonstrated that caregivers of patients with CAR T cell therapy experience significant levels of anxiety and burden and often support services have not evolved to support patients or caregivers receiving these novel treatments.[5] As a result of patients’ risk of serious physical health consequences, caregivers can experience substantial psychological burden, often in new contexts. Further, there are frequent gaps in communication around CAR-T therapies, leaving patients and caregivers with misperceptions about patient prognosis, which can complicate coping and care plans.[6, 7] This is especially concerning as care moves to outpatient settings,[8] where caregivers will have more responsibility for patient care and safety.

Prior work suggests there is strong interdependence between physical and psychological outcomes in cancer, as well as patient and caregiver outcomes.[9, 10] For example, when patients are distressed, there is an increased likelihood for caregiver distress, and vice versa. Similarly, increased caregiver distress is associated with poorer self-reported caregiver health, which in turn is related to poorer patient outcomes. The relationships between these outcomes can also be influenced by social contextual factors, such as relationship characteristics and processes or social determinants of health and social needs.[11] However, to date, little work has explored the patient and caregiver experience of cancer CAR-T treatment within this framework.

The purpose of the current study is to describe the cancer CAR-T experience of patients and their caregivers with specific attention to individual, relational, and contextual factors that may have had an impact.

Methods

Patients receiving CAR-T therapy at an NCI-designated Comprehensive Cancer Center and their caregivers were recruited in 2021 as part of a larger study. Participants were recruited and enrolled within a week of hospital discharge. Demographic questionnaires were collected at enrollment and semi-structured interviews were conducted by author DK, a trained senior qualitative researcher, with patient-caregiver dyads by zoom/phone as close to 7 days after hospital discharge as possible. Interview questions included a general inquiry around the participant’s time receiving treatment or as a caregiver and what was seen as helpful or could be improved to be more supportive. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by Advarra IRB and Moffitt SRC (MCC 21081).

Data analysis

Data included analytic memos[12] taken during and after the interviews, and transcribed interviews. Analysis, as described next, closely followed the steps and principles of thematic analysis as described by Braun and Clark.[13] Interviews were first read in their entirety by two additional members of the research team (IL and DT) to immerse themselves in the data through close readings. Next, following the constant comparison method,[14–16] code and theme concepts were discussed by manuscript authors, who met multiple times to discuss potential inductive codes. Additionally, deductive codes were selected using the Dyadic Cancer Outcomes Framework.[11] This framework guided the way that we interacted with, interpreted, and present the data. The Dyadic Cancer Outcomes Framework highlights the relationship context of the dyad, the broad social context, and a wide range of dyadic and individual-level outcomes, which were adopted as themes. Multiple iterative meetings and refinement of codes resulted in a codebook that was then applied to each transcript by coders using NVIVO R1.[17] Discrepancies in coding were discussed to help refine and consolidate coding categories and add any additional inductive codes in conjunction with the larger team. A process of compiling of analytic memos and documentation of coding in an audit trail was used. Finally, key themes were developed from the coded data.

Results

A total of 10 patients and 9 caregivers participated in interviews (Mean=49, SD=27 minutes). Participant characteristics are described in Table 1. Interview data yielded three main themes focused on the CAR-T therapy experience at the individual level, relational aspects of treatment, and contextual factors.

Table 1.

Patient and Caregiver Demographics

	Patients (n=10)	Caregivers (n = 9)
	M (SD)	M (SD)
AGE, YEARS	62.90 (8.09)	49.12 (14.84)
SEX	N	N
MALE	7	3
FEMALE	3	6
SEXUAL ORIENTATION
STRAIGHT OR HETEROSEXUAL	9	8
LESBIAN, GAY, OR HOMOSEXUAL	1	1
RACE
AMERICAN INDIAN OR ALASKA NATIVE	0	1
BLACK OR AFRICAN AMERICAN	2	1
WHITE OR CAUCASIAN	8	8
ETHNICITY
NON-HISPANIC	9	8
HISPANIC	1	1
EMPLOYMENT STATUS
WORKING MORE THAN 35 HRS./WK.	5	6
WORKING LESS THAN 35 HRS./WK.	1	0
RETIRED	3	2
ON MEDICAL OR OTHER LEAVE	1	0
STUDENT	0	1
LEVEL OF FORMAL EDUCATION
LESS THAN HIGH-SCHOOL DIPLOMA	2	0
HIGH SCHOOL OR EQUIVALENT	1	0
SOME COLLEGE	1	2
FOUR YEAR DEGREE	2	4
POST-GRADUATE DEGREE	4	3
FINANCIAL SITUATION
NOT VERY COMFORTABLE	1	0
MORE THAN ADEQUATE	1	2
COMFORTABLE	8	6
MISSING	0	1
PRIMARY HEALTH INSURANCE
MEDICARE	3	2
MEDICAID	1	0
INSURANCE FROM OWN/SPOUSE EMPLOYER	5	5
PRIVATE INSURANCE	1	1
OTHER GOVERNMENT PLAN	0	1

Individual

The CAR-T therapy experience impacted patients and caregivers differently on an individual level. Patients primarily described their physical state, focusing on symptoms and their management.

Patients reported being prepared that the treatment journey would be unpredictable, “The nurses warned me that there might be peaks and valleys” (ID003, male, 61 years). Not all patients reported experiencing adverse events, yet most did report significant debilitation in response to treatment, at least during parts of the treatment:

Day 4 I started fevers and became very weak. For the next three days or so I was very weak, very debilitated. Having some fevers and couldn’t get up and move or do much of anything…But my experience was mixed because I did feel very good at the beginning and I felt pretty good at the end … But those three days or so were pretty rough. (ID 009: Patient, female, 70 years)

I was walking two miles a day for the first three days that I was there and then all of a sudden I just wasn’t able to do it, so it was very difficult for me to manage. I hated being what I call a bed slug, just lying there. I describe it as feeling like a fish that’s flopped up on a dock after being caught and you just can’t do anything; you’re helpless. (ID 009: Patient, female, 70 years)

While caregivers mentioned the patient’s physical symptoms as well, they more often focused more broadly on the overwhelming nature of their role, which required round the clock involvement, often on top of other competing responsibilities.

Honestly, there was not really, there wasn’t any time for myself… every day we’re driving back and forth to the hospital. And even though we live close, that’s still 45 minutes one way out of your day. And it’s 45 minutes that I have to make up for work when I’m on the road. (ID 1005: Caregiver, Female, 57 years)

When she comes home, you got to treat her just like a newborn baby. And that you cannot leave her for one second. I thought to myself, ‘Well, you can even leave a newborn baby in the crib to sleep while you go in another room’. (ID 1016: Caregiver, Male, 80 years)

Similarly, caregivers also discussed feeling like they were operating without a sufficient understanding of the information communicated to them, either because there was too much information provided, or not enough.

When you’re sitting in front of [an oncologist]… I won’t say he talks over your head, but he gives you so much information in such a short amount of time that you can only filter and process so much that you’re missing – for me, I’m missing 30-40% of what he was saying because I was focused on what he was saying three sentences ago. (ID 1005: Caregiver, Female, 57 years)

I think that maybe there should have just been some more information given, “if you experience this, this is the process that we normally see.” So that, for the average person, you’re not stumbling around in the dark thinking, “what’s gonna happen?” And then you just see somebody just suddenly deteriorate. And then at that point you don’t know whether they are going to die or if there’s gonna be a turnaround. (ID 1011: Caregiver, Male 46 years)

Relational

The relational component of the CAR-T experience was most frequently commented on by caregivers. Building off the individual theme of feeling overwhelmed, one relational theme focused on the patients’ improvement making the work feel worthwhile.

“[Caregiving tasks were] okay for me, I could do it and it wasn’t that big a strain for me, but I can see if you had a patient in there that you loved for 45 days or in the hospital not recovering, that day to day drip would wear you out.” (ID 009 1009: Caregiver, Male, 69 years)

Caregivers also recognized that sometimes treatment side effects could strain the relationship:

When she got to a point to where she wasn’t getting any sleep and some of the meds made her irritable…I was like, “You understand the medication makes you irritable, right?” And she’s like, “Yes, I know.” And I’m like, “Well, who do you think you’re taking it out on?” (ID 1015: Caregiver, Female, 42 years)

Participants commented on how the enforced time together impacted their relationship in different ways. For some, it strengthened the relationship:

I think it’s been great for both of us. I think we communicated a little bit better during the times that I was going through, and I hope it brought us a little closer. (ID 005: Patient, Male, 59 years)

However, others reported breaks from each other while the patient was in the hospital were sometimes helpful.

There’s something about that separation of okay, that’s where she is, I know she’s being taken care of… it’s kind of a good mental getaway for me to get away and do something else. (ID 1009: Caregiver, Male, 69 years)

Contextual

Participants also recognized the social determinants and social needs required to participate in CAR-T therapy, particularly access to food, housing, and travel costs. Obtaining temporary housing after treatment was a central logistic challenge for patients and caregivers during the treatment phase. One participant recognized her privilege in having access to support for these resources.

I was overwhelmed with how people have been, how we’ve been taken care of, you know, from food to our place to stay. We couldn’t have afforded to be over here for a whole month in an apartment. But we had to stay close, and so, I mean, wow. Just feel totally blessed by that. (ID 1013:Caregiver, Female, 58 years)

Another participant recognized the added complexity housing added to the treatment experience:

Well, we were in a hotel because we needed to stay close. So, when we left after the inpatient side, we stayed in a hotel. And then I had to be readmitted…She was able to stay in the hotel for a little bit while I was in the hospital …And then we stayed a couple extra days in the hotel… I’m now a completely displaced individual. (ID 014: patient, Male, 60 years)

Access to transportation was another additional barrier, even for individuals who did not live far away:

For me, I cannot drive here. So, I have to catch an Uber every day. That’s kind of expensive… I had called my social worker to find out if there was any kind of grant I could get… but [the grant] was for gas on my car. I couldn’t use it for an Uber. After you get the CAR T-cells, you can’t drive for eight weeks. (ID 015: Patient, Female, 58 years)

Discussion

CAR-T holds important promise for cancer treatment. Research on the patient and caregiver experience can shed light on how to shape expectations and provide education. Our findings suggest that while there may be experiences that are unique to this therapy, such as the unique symptom burden and the intensiveness of caregiver observation required, many of the broader relational and contextual factors are similar to what patients and caregivers receiving other treatments report, but may be augmented by the shorter but more intensive nature of the experience and the medical complexity of many patients who receive CAR-T[18]. This suggests that although treatments for cancer have advanced, there is still a need for more attention to patient and caregiver holistic needs that can ultimately impact treatment adherence and long-term success.

For example, symptom management is a key area of concern for most cancer patients. Research suggests that there is a unique symptom burden associated with CAR-T and often associated with cytokine release syndrome, including pain, fatigue, lack of appetite, and headache.[19, 20] Although these symptoms may be less intense and resolve faster than other types of treatment,[21] they have been shown to impact quality of life and patients often underestimate their impact.[22] Research has also shown difficulty in providing the right level and type of information to caregivers at different stages and within the dynamic context of cancer care.[23, 24] Our results suggest that this balance has not yet been achieved, and caregivers were unprepared not just for the patient’s symptom trajectory, but also for the level of vigilance required on their part, often resulting from uncertainty.[25]

Our participants also noted that the intensive treatment experience, when patients and caregivers were frequently isolated together, impacted their relationships, echoing established research. High quality relationships can serve as a strength in coping with cancer,[26, 27] but changes in roles both patients and caregivers take on can be difficult and create additional stress.[28–30] As seen in our sample, some patients and caregivers grew closer together, but often stressors associated with treatment weighed on relationships. Some evidence suggests that there is a need for broader support and preparation for caregivers to protect against burden and negative impact on quality of life.[31, 32] This may be particularly true for CAR-T caregivers, who are asked to take on an intensive caregiving role and are often isolated from their social network during the most difficult phases of care. Caregiving responsibilities can be shared[33], yet this can be difficult when isolated for treatment.

As such, support from healthcare team can become critical, yet our data suggests that there were missed opportunities. Patients and their families did not always feel properly prepared for the potential implications of their treatment, much of which comes down to communication and education from the healthcare team.[22] Additionally, healthcare providers may overlook how treatment intersects with relationship and contextual factors. Increased opportunities for community and peer support in group housing, such as through the American Cancer Society Hope Lodge program, or support groups and other caregiver programs, may be important provide support and prevent isolation.[34–36]

Social determinants of health and social needs can also impact whether patients are even offered treatment, and the experience of those who receive it. One limitation of our study is that our sample is relatively small, represents only those treated at one NCI-designated Comprehensive Cancer Center and lacks racial and economic diversity. Innovative treatments such as CAR T-Cell therapy are not available at all cancer treatment facilities and high costs can make available treatment inaccessible.[37] This is especially true for historically marginalized and minoritized populations who—even when treatment costs are covered by insurance--may also struggle to afford other costs associated with treatment, such as housing, food, or transportation, which are not covered by insurance.[38] Similarly, the intensive requirements of care and the potential need to relocate for treatment means that caregivers may be unable to work. As such, novel treatments such as CAR-T, may widen disparities due to the high costs and intensive caregiving need preventing access for some segments of the population. There is a need for paid time off to help caregivers recover lost wages or compensate for their important role in cancer treatment. Financial and workplace security for caregivers is part of the 2022 National Strategy to Support Family Caregivers,[39] yet to date no legislation has been enacted in this area.

Clinical implications

Caregivers and patients in this study reported being overwhelmed with information for this new and potentially life-threatening treatment. Clinical care teams must tailor their educational material to be comprehensive and comprehensible. Participants also reported struggling with issues that might be traditionally seen as outside the realm of cancer care: relationship/role adjustments, housing, food, and travel. Oncology social workers and other clinical staff, such as navigators or psychologists, are critical assets in helping connect patients and caregivers to services to address these issues, yet often do not receive the time or tools to adequately address the holistic factors that are integral to the health and well-being of patients and caregivers. Better integration and support for more wraparound clinical support services could translate to more complete patient and caregiver care.

Data availability:

Data is available upon reasonable request to the corresponding author.