Adkins Discusses Benefit of Second-line CAR T-Cell Therapy in Large B-Cell Lymphoma


Sherry Adkins, MSN, ANP-C, discusses the significance of incorporating CAR T-cell therapy regimens, such as lisocabtagene autoleucel, into earlier lines of treatment for patients with relapsed/refractory large B-cell lymphoma.

Sherry Adkins, MSN, ANP-C

Sherry Adkins, MSN, ANP-C

The approval of lisocabtagene autoleucel (Breyanzi; liso-cel) for the second-line treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) represents an exciting shift in care allowing for earlier delivery of personalized medicine, according to Sherry Adkins, MSN, ANP-C.

The FDA recently approved liso-cel based on findings from the phase 3 TRANSFORM study (NCT03575351), which showed that patients who received the CAR T-cell therapy had significant clinical improvement compared with the standard of care of the past 20 years—salvage therapy followed by high-dose chemotherapy plus autologous stem cell transplant (ASCT).1

In an interview with Oncology Nursing News®, Adkins, a nurse practitioner in the Department of Myeloma and Lymphoma at University of Texas MD Anderson Cancer Center, discussed the significance of the approval. Adkins is the supervisor for the advanced practice providers who work with patients receiving CAR T-cell therapy at MD Anderson and has firsthand experiencing working on several CAR T-cell therapy clinical trials, including ZUMA-1 (NCT02348216), which led to the release of axicabtagene ciloleucel, the first commercial CAR T-cell therapy for the treatment of lymphoma.

Oncology Nursing News®: What is the significance of the FDA approval of liso-cel in the second-line setting for patients with relapsed/refractory LBCL?

Adkins: I am really excited that we now have a second-line CAR T-cell therapy for this patient population. Relapsed/refractory disease is known to not respond well to traditional therapies. The sooner we can give this therapy, the better the outcome.

We know from previous studies that patients who receive a lot of prior therapies do not have as robust T cells. With T cells [that] have been exposed to a lot of treatment, the outcome [may] not be as good as if we had healthy T cells.

Moreover, for patients with relapsed/refractory [disease], the chances of responding to traditional therapies is not very good. The sooner we can get to a targeted therapy the better, because then we have a decreased risk for the development of secondary malignancies—­­such as myelodysplastic syndrome and leukemia.

[Regarding] the cost of care, we know that this high-risk population is [probably] not going to respond to chemotherapies, [so if] we keep giving other chemotherapies until we get to the third line, then that is going to cost more for the health care system. There are a lot of positives about moving these therapies closer to the frontline.

Please comment on findings from TRANSFORM trial regarding liso-cel vs high-dose salvage chemotherapy and ASCT. What about the findings stood out to you?

The primary end point of the TRANSFORM study was event-free survival [EFS]. The median EFS for liso-cel was 10.1 months vs [2.3 months] with standard-of-care high-dose chemotherapy with ASCT [HR, 0.34; 95% CI, 0.22-0.52, P < .0001]. [The median] progression-free survival [PFS] for liso-cel was more than twice the standard-of-care arm; 14.8 months vs 5.7 months, [respectively; HR, 0.41; 95% CI, 0.25-0.66; P = .0001].2

This is very exciting. We can see there is a big difference between these 2 therapies and it's great for the patient. It’s also important to note the objective response rate (ORR) for liso-cel was 86% vs standard of care which was 48%. And the complete response for liso-cel was 66% vs standard of care at 39%. The outcomes [were] definitely better for the liso-cel group.

We also saw acceptable toxicities. We do not want to have any toxicities, but for second-line therapy, the toxicity rate was even better than for patients in the TRANSCEND-NHL-001 study [NCT02631044]. The number of patients who had all-grade [cytokine release syndrome] CRS was approximately 45% [and] only 1.3% of patients had grade 3 or greater CRS. The findings were also great for neurotoxicity. The rate of all-grade neurotoxicity was 27%. For grade 3 or greater, the rate was only 7%. This is really great for the patients: good efficacy and less toxicity.

Now that CAR T-cell therapy is becoming more prominent, real-world datasets are showing that patients outside of the strict clinical trial criteria also benefit from this therapy. Which factors would providers need to weigh when deciding when to administer liso-cel?

The real-world data is very similar to the survival [data] in the clinical trials. There are a few things that are a little bit different, but in general, that is the case.

There are 2 factors that have been found affect both PFS and overall survival: the ECOG status and [lactate dehydrogenase] LDH levels are the key factors to look at in terms of patients having a positive outcome.

At MD Anderson, we review all patients who are going to [receive] commercial CAR T cells and we look at multiple factors. If they’re above the age of 65 years or their ECOG [performance status] is not good, we send them to a program called prehab to try to “tune them up” and get them ready for CAR T-cell therapy. We also look at their [glomerular filtration rate] GFR. If it is less than 50, that would be considered high risk. That helps us determine if there is a better product to use in that population.

Other [potential risk factors] include absolute monocyte counts less than 1000, platelet counts less than 50, a pulmonary function test detail less than 40, or ejection fraction less than 45%. If they have arrhythmias that are uncontrolled and a low ejection fraction, we also consult our cardiology group to try to see if there’s anything that we can do to “tune them up” quickly so that they can move on to CAR T-cell therapy.

We give CAR T-cell therapy to patients who have secondary CNS involvement, but not to those who have primary CNS. We also look for evidence of secondary malignancies that have been treated or are currently being treated.

Please comment on later care following treatment such as transitions to a community care setting or potentially persistent transfusion dependency.

The majority of patients are receiving CAR T-cell therapy at specialized centers, which are typically not in their hometown. Once the required 30-day stay after receiving the therapy…they travel back home.

It is very important that we communicate information to the local oncologist or [primary care provider]. Some [patients] don’t have an oncologist—we hope that they can find one, but some come from small areas with no oncologist. It is important [that] we communicate information to caregivers and physicians who are there providing follow-up care for these patients.

They need to know that it is not unusual for the patients to have low blood counts for quite [some time] after this therapy [and] they may recover their cell count and then drop again later related to an immune-mediated effect. It’s important to know if they can give growth factors, and when we would recommend transfusing patients for anemia and thrombocytopenia.

Also, it is important that they know what prophylactic antimicrobials the patient should be [receiving]. At MD Anderson, our guidelines are that we treat patients with antiviral and anti-pneumocystis pneumonia prophylactically for 1 year post CAR T-cell therapy and at that point we measure the CD4 count. If it is less than 200, we continue with that prophylaxis, because we did see early-on that a large percentage of patients were developing shingles post CAR-T cell therapy [after being] taken off their antiviral prophylaxis. Those are all important things for the local caregivers to know.

It is important for the patient to know [this information as well.] I encourage my patients to take a copy of the letter that we send to the physicians and to keep it on their person. If they ever need to go to the emergency department, they can present that to the emergency department to help [the care team] understand some things about [their] CAR T-cell therapy.


  1. US FDA approves Bristol Myers Squibb’s CAR T cell therapy Breyanzi for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. June 24, 2022. Accessed August 2, 2022.
  2. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, versus standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (Pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL): results from the randomized phase 3 Transform study. Blood. 2021;138(suppl 1):91. doi:10.1182/blood-2021-147913
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