Overcoming Caregiver Barriers in CAR T-Cell Therapy Referrals in DLBCL

Priyanka Pophali, MD, MBBS

Chimeric antigen receptor (CAR) T-cell therapy presents both innovative opportunities and significant challenges in treating relapsed diffuse large B-cell lymphoma (DLBCL). A virtual Case-Based Roundtable meeting highlighted barriers to CAR T-cell therapy referrals, particularly caregiver requirements, with Priyanka Pophali, MD, MBBS, emphasizing creative solutions like splitting caregiver responsibilities or utilizing inpatient care during high-risk periods. The discussion, moderated by Dr Pophali, an assistant professor at the University of Wisconsin, was held with other oncologists from Wisconsin and Minnesota.

CASE SUMMARY

• A 67-year-old man presented with fatigue, back pain, and lymphadenopathy.
• Medical history: Hypertension is well controlled with medication​.
• Physical exam: Left posterior cervical, 1.5-cm node; right anterior cervical node, 2.5 cm; left supraclavicular node, 2.0 cm​
• PET-CT scan: multiple enlarged mesenteric and retroperitoneal nodes, with the largest being 5.3 × 3.1 cm​.
• Bone marrow biopsy: negative​
• Lymph node biopsy: confirmed DLBCL, non-germinal cent B-cell, double expressor lymphoma.
  • Immunohistochemistry (IHC) positive for: CD20, BCL-6, BCL-2 (50% of cells), MYC (> 40% of cells), Ki67 85%, MUM1​
  • IHC negative for: CD10​
• Fluorescence in situ hybridization: negative for translocations involving MYC, BCL2, BCL6​
• Laboratory results: Lactate dehydrogenase elevated, complete blood count normal​
• Stage III; non-germinal center
• International prognostic indicator: high-intermediate risk
• ECOG performance score: 1 ​
• Rituximab (Rituxan), cyclophosphamide, hydroxydaunomycin, vincristine sulfate (Oncovin), and prednisone was initiated for 6 cycles.
• Back pain resolved​
• Post-treatment PET scan demonstrated a complete response with a Deauville score of 2; patient was observed​ after.

Eight months after completion of therapy​

• The patient complained of fever, night sweats, and back pain. ​
• A palpable lymph node in left groin was discovered on physical examination​.
• PET and CT scan: new left inguinal lymph node, increase in size of residual nodes, as well as multiple metabolically active lesions in lymph nodes of the retroperitoneum, abdomen, and pelvis​.
• Biopsy confirmed DLBCL, but next generation sequencing was not performed.
• The patient was referred to nearest transplant and cellular therapy center for evaluation

DISCUSSION QUESTION

What disease- or lifestyle-related patient factors, are significant in your decision-making?

Priyanka Pophali, MD, MBBS: It might be helpful to know, because I know that when I see patients for a consult, they generally want to talk to their oncologist before making a decision. So even though I'm talking to them about CAR T-cell therapy, they always ask if they can go back to see their doctor and then get back to me with the decision? They put a lot of trust in the relationship, and so I think having thoughts about lisocabtagene maraleucel [liso-cel; Breyanzi] vs axicabtagene ciloleucel [axi-cel; Yescarta] does matter, even though you're not the physician making the choice of that regimen, because the patient sometimes looks to it to you for that discussion.

Would you make a choice among the non–CAR T-cell therapy options based on any of these things?

Balkrishna N. Jahagirdar, MBBS: A lot of these patients have received polatuzumab vedotin [Polivy] as first-line therapy. This patient could have received it, [so] then I don't want to use it. Bendamustine would deplete the T cells, so I would avoid that. With tafasitamab [Monjuvi]/lenalidomide [Revlimid], the lenalidomide portion is not always easy on patients, although the effectiveness is more or less the same. Bispecific antibodies vs gemcitabine/oxaliplatin plus rituximab... then another bispecific plus chemotherapy option as well, which is evolving now. We prefer options, but I think the first bifurcation point for me is to decide what I want to do is, is this patient ever going to have CAR T cells or not? Because this is the time to do it now, because it's one and done for now.

Pophali: Is the decision for CAR T center dependent? If you're referring to different centers, do you feel like some centers prefer one type of CAR T vs others, or is it patient by patient that you've seen selection of CAR T products, whether axi-cel or liso-cel?

Jahagirdar: I think it's patient by patient for the most part. I don't see a big difference. All of us here in this region, it's either Mayo Clinic or University of Minnesota, and I have not seen a difference in the opinion there.

Shahid Shekhani, MD: Most of the last few years that we have done a CAR T-cell therapy were based on a clinical trial. So depending on which center had which trial, patients were getting put in that. But now, since most of these medications are in clinical practice, even in bispecific antibodies—I've sent 2 patients to University of Wisconsin, and both got different bispecific therapy. Is it a physician preference?

Pophali: Whether it's the physician preference or patient factors that come into play, that's the part we need to think about or ask, if it's not clear.

Shekhani: In multiple myeloma, I think the newer one has a shorter period that you have to do induction, and then you can get them quickly on the maintenance therapy, because the patient wants to come back to the community setting after induction. So some of those factors are in play.

DISCUSSION QUESTION

In which instances would you consider continuing to manage this patient with DLBCL vs referring for CAR T-cell therapy in the second line?

Pophali: [There is] patient preference or inability to travel. Are there other situations you deal with where you would continue to manage the patient vs sending to a CAR T-cell center?

Abdel Alqwasmi, MD: I typically offer for them and encourage them, at least, to have that visit with the CAR T-cell physician, and unless they completely decline or they make that first visit and they are deemed not eligible, I always encourage them to do so.

Gordon J. Ruan, MD: One challenge is having the caregiver support. I recently learned from a separate workshop that some of these societies have volunteers who could help out to be a caregiver for either transplant or CAR T-cell therapy. I'm not sure if you've had any experience there.

Pophali: No, I'm interested in which societies we're talking about here.

Ruan: It was the Leukemia & Lymphoma Society that someone mentioned. I'm not sure if any of the other community physicians have had experience with this, but that was something that was news to me, because in my mind, if a patient did not have a caregiver, then that would certainly be a significant barrier to disqualify them. But if there are ways around it, such as having volunteers who could help out, that would certainly change things.

Pophali: My experience is that most of the time when we discuss CAR T and the requirement to have a caregiver for 4 weeks, the initial gut reaction for patients is that's too much to expect from someone. Sometimes talking with the social worker, trying to come up with a calendar of individuals who could maybe not spend the full time, but parts of the time as the caregiver [can work]. I would say 80% of patients were able to piece together a caregiver plan. Sometimes we've had patients who have the resources to hire a caregiver. Other times, we have relied on friends.... In that case, to minimize the burden, sometimes we treat them as inpatient for the first 2 weeks, which is the highest risk of having cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome complications, 1 to 2 weeks. Then they just need to have someone check in on them rather than be with them 24/7.

There are ways around that caregiver issue sometimes, and we have to have that conversation to understand the patient's situation. If a patient is absolutely alone without anybody, the caregiving becomes challenging, but I would say that number is probably 5% or less, where we absolutely cannot take a patient to CAR T because of lack of caregiver. I think that is an injustice to the patient and the disease they're dealing with, so we do our very best to try and figure that out. Resources like the Leukemia & Lymphoma Society, it's helpful to know that they may have some program to support patients through this.

I would sometimes let the CAR T center explore that, because once you put in a CAR T consult, typically, that comes with the social work consult and a nurse navigator consultant. They have a lot of experience in terms of figuring out the resources, whether it's monetary limitations for accommodation, food, things like that, vs a caregiver. That can happen, and...telehealth has definitely changed some of my practice in the sense that with patients who are very hesitant, sometimes we offer them that telehealth visit just to have the conversation and then decide whether they want to even pursue CAR T or not, but [these are] very good points. I think [having a] caregiver is one of the barriers sometimes.