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Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

38013297
00041
10.1097/MD.0000000000036067
3
5700
Research Article
Observational Study
Nursing care of patients with relapsed and refractory multiple myeloma treated with B-cell mature antigen-targeted universal chimeric antigen receptor T cells
Dai Ying Bachelor 38552033@qq.com
a
https://orcid.org/0009-0006-1470-1299
Tang Fang Bachelor a*
Mao Yanqin Bachelor maoyanqin@suda.edu.cn
a
He Na Bachelor hena@suda.edu.cn
a
Yu Meimei Bachelor 854853988@qq.com
a
Zhang Mengjiao Bachelor 354934986@qq.com
a
Gu Sumei Bachelor 2806154251@qq.com
a
Lu Yin MSN luyin@suda.edu.cn
a
Shang Jingjing MD rebeccasjj@163.com
a
Zhu Xiamin Bachelor zhuxiamina@163.com
a
a Nursing Department, Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
* Correspondence: Fang Tang, Nursing Department, Department of Hematology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, China (e-mail: tf_1980@126.com).
24 11 2023
24 11 2023
102 47 e3606703 8 2023
18 10 2023
20 10 2023
Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
2023
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

To investigate the efficacy of a nursing approach using B-cell maturation antigen (BCMA)-targeted universal chimeric antigen receptor T-cell (BCMA-UCART) immunotherapy in the treatment of 16 patients with relapsed refractory multiple myeloma (MM). In this study, 16 patients with relapsed and refractory MM who were treated with BCMA-UCART and BCMA-CART in our department from May 2020 to November 2022 were selected, and were divided into a control group and an experimental group of 8 cases each according to the difference in the nursing methods, and the control group adopted the conventional universal nursing program. The experimental group used the nursing protocol that cooperated with the immunotherapy of this study, and the main points of nursing care included timely assessment of organ functional status, safe and accurate infusion of BCMA-UCART, identification and management of hyperthermia, hypotension, arrhythmia and central nervous system adverse reactions caused by cytokine release after BCMA-UCART infusion, as well as management of fluid imbalance, maintenance of stable blood pressure, and cooperation with physicians to effectively control of inflammatory factors. In addition, patients were provided with psychological and dietary support. The duration of hospitalization was compared between the two groups after the intervention. The discharge time of the experimental group was significantly shorter than that of the control group (P he.05), and the experimental group effectively controlled cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and acute graft-versus-host disease. The nursing program with BCMA-UCART immunotherapy is effective in intervening MM patients and promotes their early recovery and discharge from the hospital.

BCMA
multiple myeloma
nursing
universal chimeric antigen receptor T cells
OPEN-ACCESSTRUE
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pmc1. Introduction

Chimeric antigen receptor T (CAR-T) cell therapy has allowed for remarkable therapeutic gains in anti-tumor therapy, especially in hematological malignancies. It has facilitated significant, long-term anti-tumor effects with higher target specificity. However, autologous CAR-T cell therapy has some limitations, such as high cost, a long manufacturing cycle, and a limited cell source. The development of universal CAR-T (UCART) cell therapies may overcome these shortcomings.[1] From May 2020 to November 2022, 16 patients with relapsed refractory multiple myeloma (MM) admitted to our department were treated with BCMA-UCART and BCMA-CART with different nursing interventions as follows.

2. General information and methods

2.1. General information

We selected 16 patients with relapsed and refractory MM who received B-cell maturation antigen (BCMA)-targeted UCART and CART treatment in our department from May 2020 to November 2022. They were divided into a control group and an experimental group of 8 cases each according to the different methods of nursing care, with the control group adopting the conventional universal nursing program and the experimental group adopting the nursing program in conjunction with the immunotherapy of this study. The control group: 4 men and 4 women, aged 33–71 years; the experimental group: 5 men and 3 women, aged 45–71 years. There was no significant difference in the general information of the 2 groups (P >.05), and all of them were diagnosed with recurrent and refractory MM; the diagnosis met the criteria of the literature.[2] Before enrollment, the MM cases were treated with at least 3 regimens, including at least one protease inhibitor and one immunomodulator without a complete response. The study was approved by the Ethics Committee of our hospital [approval No.: (2021) LUN Approval No. 205, (2022) LUN Approval No. 162], and informed consent of patients and their families was obtained.

After admission, relevant physical and imaging examinations were performed, and the patients’ physical and mental conditions were assessed. Before infusion, an FC regimen (once daily intravenous fludarabine 30 mg/m2/day x3 days and cyclophosphamide 500 mg/m2/day x3 days) was used to deplete lymphocytes. White blood cell and lymphocyte counts were monitored, hydration and alkalization assistance provided as needed, and various protective measures implemented to prevent opportunistic infections in patients. BCMA-UCART cells were transfused back to the patients 1–2 days after the depletion treatment. Vital signs and oxygen saturation were monitored 15 minutes before infusion, then 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after infusion. Patients with fever, headache, palpitation, dyspnea, or other discomforts were treated as appropriate.

All patients completed the BCMA-UCART cell infusion. Of these, three became febrile on the 7th and 8th day after infusion, with the highest temperature of 40°C, and included 3 cases of cytokine release syndrome (CRS) (1 each of grade 1, 2, and 3). One patient showed immune effector cell-associated neurotoxicity syndrome (ICANS), and 1 patient developed acute graft-versus-host disease (GVHD), both of which were treated promptly allowing for a timely discharge from hospital.

2.2. Methods of care

The control group used the general routine clinical nursing program of infusion, blood transfusion, anti-infection and so on. The experimental group used nursing protocols that complemented the immunotherapy of this study: timely assessment of organ functional status, safe and accurate infusion of BCMA-UCART, identification and management of hyperthermia, hypotension, arrhythmia and central nervous system adverse reactions caused by cytokine release after BCMA-UCART infusion, as well as management of fluid imbalance, maintenance of blood pressure stability and effective control of inflammatory factors in cooperation with physicians. It also includes psychological and dietary support by the patient.

2.3. Observation indicators

Compare the hospitalization time of the patients in the 2 groups after the intervention; observe the changes in the condition and recovery of the experimental group during the intervention period.

2.4. Statistical methods

Analyzed by SPSS22.0 software, the measured data were shown as ±as and compared by t test. Differences were considered statistically significant at P es.05.

3. Results

3.1. Comparison of hospitalization time between the 2 groups after the intervention

After the intervention, the length of hospitalization was (36.4+/-9.2) in the control group and (27.8+/-12.9) in the experimental group. and the length of hospitalization in the experimental group was significantly shorter than that in the control group (t = 4.453, P <.05).

3.2. Changes in the condition and recovery of patients in the experimental group during the intervention period

Two of the 8 patients in the experimental group initially carried heavy psychological burdens and exhibited fears related to their condition. However, through active psychological counseling, these patients were able to relax and successfully complete the treatment process. Grade 1 CRS the patient (n e 1) developed fever (up to 40°C) with chills and nausea but no vomiting on day 8 after BCMA-UCART cell infusion. During the fever, the patient was flushed, had shortness of breath, and an accelerated heart rate. In addition to monitoring his vital signs (including temperature), the patient was provided with appropriate insulation and bedside protection to prevent the patient from falling during chills. The patient was given routine blood and urine tests, blood cultures, and chest X-rays as prescribed. The patient was washed with warm water and medication changed as appropriate, and indomethacin was administered to lower the body temperature. The fever subsided after 4 days. The patient with grade 2 CRS (n he1) developed fever on day 7 after the infusion and then hypoxemia (oxygen saturation of 89%) on day 8 with nausea without vomiting, chills and shivering, but no chest tightness or shortness of breath. Respiratory secretions were promptly removed. Physical hypothermia and acetaminophen or other antipyretics were used to lower body temperature. Tocilizumab is used to treat CRS and the patient is concerned about the possibility of an allergic reaction. Patients’ temperatures and blood oxygen returned to normal 2 days after tocilizumab treatment and did not recur. CRS grade 3 patients (n RS1) developed fever (up to 39°C), chills, nausea, and vomiting on day 8 after the infusion. On day 10, they developed hypoxemia (oxygen saturation 88%) and hypothermia with a blood pressure of 77/45 mm Hg. They were supplemented with oxygen at a rate of 3 liters/minute, monitored with an electrocardiogram, and their infusion was prolonged with 1000 mL of Ringer solution. Intravenous dexamethasone 10 mg and norepinephrine 18 mg/50 mL NS at a dose of 3 mL/hour were administered to stabilize blood pressure; after 2 days of treatment, the patient temperature and oxygen levels returned to normal, and her blood pressure was maintained at 100–110/70–75 mm Hg with no other symptoms. The Immune Cell Associated Encephalopathy 10-grade scale is commonly used to grade the severity of ICANS. One patient in the experimental group experienced grade 1 ICANS, which is characterized by a decrease in computational ability, the main manifestation of CRS. The patient was closely observed for changes in her state of consciousness and her airway was kept open. The patients were provided with oral levetiracetam, intravenous tocilizumab, and glucocorticoids as recommended by their physicians. On the next day, their symptoms disappeared. In addition, 1 patient in the experimental group developed GVHD grade 3 days after the infusion of BCMA-UCART cells, which manifested as head and neck rash, nausea and diarrhea. We used the grading criteria of the International Acute GVHD Association to assess the patient as a whole, closely observing each grade for early recognition and early intervention. The patient was managed by ensuring that the skin was kept dry and clean, avoiding heat, and providing fluids and vitamin C supplements. The patient was given glucocorticoids as prescribed. After 3 days, symptoms resolved, the rash subsided, and nausea and diarrhea decreased.

4. Discussion

This paper discusses the nursing care of patients with relapsed and refractory MM treated with B-cell mature antigen-targeted universal CAR-T, and intervenes in the 2 groups of patients with different nursing protocols, respectively, and the results show that the length of hospitalization in the experimental group is significantly shorter than that in the control group, and the difference is statistically significant. The result suggests that the nursing program with the immunotherapy of this study is effective and can promote the early recovery of MM patients. Analyzing the reasons, it may be related to the following contents included in the nursing program of the experimental group. Mental nursing: Patients who underwent BCMA-UCART cell immunotherapy had previously experienced poor treatment outcomes from at least 3 regimens, leading to significant mental and financial pressures for both patients and their families. Therefore, it is crucial for nursing staff to prioritize assessing and understanding the unique psychological needs of each patient during pretreatment sessions. Establishing a strong nurse-patient relationship is essential, as it allows nurses to explain the necessity and feasibility of the treatment, discuss potential adverse reactions, and outline the corresponding treatment strategies. This approach helps increase patients’ confidence in overcoming the disease. Dietary nursing: At present, there is no evidence that a proper diet has a direct therapeutic effect on MM. However, a proper diet can ensure adequate energy intake and alleviate some of the common symptoms of MM. Patients should eat fresh, light, easily digestible, soft food rich in vitamins. Patients should be encouraged to drink more water and urinate more often to reduce the incidence of hemorrhagic cystitis. If renal function is impaired, patients should adjust their diet to reduce intake of salt, protein, potassium, and phosphorus, while limiting fluid intake. In the context of anemia, patients should consider eating foods rich in iron, folic acid, and vitamin 12. In short, dietary nursing should be adjusted according to the specific physical condition of each patient to help them safely and effectively complete their treatment.

Nursing of CRS: CRS is a common complication of CAR-T therapy and occurs within 2–15 days after receiving CAR-T cell infusion. Common symptoms include fever, hypotension, hypoxia, and organ damage. CRS is graded using the consensus criteria of the American Society for Transplantation and Cellular Therapy.[3,4] Three of the 8 enrolled patients developed CRS. Nursing of acute GVHD: GVHD is a major complication after hematopoietic stem cell transplantation, mainly due to the mismatch between donor and host HLA phenotypes, manifested as a tissue and organ inflammatory response syndrome. Donor lymphocytes recognize HLA type I antigens on the surface of host cells and become activated as effector cells, secreting cytokines and mediating cytotoxic effects to attack target organs such as the skin, intestine and liver of the host, eventually causing damage to the target organs of the host.[5] UCART cells are lymphocytes derived from healthy donors that have been genetically engineered to lack the T cell receptor (TCR) gene. UCART cells do not express TCR and do not bind to HLAI-like antigens on the surface of host cells, thus preventing GVHD. However, GVHD can still occur due to limitations of the production process.[6] GVHD has been reported after UCART infusion by interfering with the normal synthesis of TCR.[7] Acute GVHD can affect the skin, presenting as maculopapular that predominantly appear on the head and neck, behind the ears, face, and shoulders. The skin serves as an easily accessible organ to observe and monitor acute GVHD changes. Patients typically present with mild pruritus and pain. The gastrointestinal tract is the second most-affected target organ in acute GVHD, manifesting with nausea, vomiting, anorexia, diarrhea, hematochezia, and even intestinal obstruction. Acute hepatic GVHD is characterized by hyperbilirubinemia due to cholestasis, with or without elevated liver enzymes.[8] One of our patients developed GVHD grade 3 days after BCMA-UCART cell infusion, presenting with a rash on the head and neck with nausea and diarrhea.

5. Conclusions

Similar to conventional CAR-T therapy, BCMA-UCART therapy for MM has similar adverse effects and care requirements. These adverse effects include fever, hypoxia, hypotension, and neurotoxicity. However, a major difference with BCMA-UCART therapy is the potential to trigger GVHD. Intervention with MM patients using a care regimen in conjunction with BCMA-UCART immunotherapy is highly effective and promotes early recovery and discharge. It is worth noting that the limited number of cases in this study may not provide a comprehensive picture of all possible adverse effects. Therefore, it is necessary to include new cases and conduct further analyses to gather more insights and improve clinical care practices for BCMA-UCART therapy.

Author contributions

Conceptualization: Ying Dai, Fang Tang.

Data curation: Ying Dai, Fang Tang, Yanqin Mao.

Formal analysis: Ying Dai, Fang Tang, Yanqin Mao, Na He, Yin Lu.

Investigation: Ying Dai, Meimei Yu, Jingjing Shang, Xiamin Zhu.

Methodology: Ying Dai, Fang Tang, Yanqin Mao, Na He, Sumei Gu, Yin Lu.

Resources: Ying Dai, Meimei Yu, Mengjiao Zhang, Sumei Gu, Jingjing Shang.

Supervision: Ying Dai, Yanqin Mao, Na He, Mengjiao Zhang, Xiamin Zhu.

Validation: Ying Dai, Fang Tang, Meimei Yu, Sumei Gu, Yin Lu, Jingjing Shang.

Visualization: Ying Dai, Fang Tang, Yanqin Mao, Na He, Meimei Yu, Mengjiao Zhang, Sumei Gu, Yin Lu, Jingjing Shang, Xiamin Zhu.

Writing – original draft: Ying Dai.

Writing – review & editing: Ying Dai, Fang Tang, Yanqin Mao, Na He, Meimei Yu, Mengjiao Zhang, Sumei Gu, Yin Lu, Jingjing Shang, Xiamin Zhu.

Software: Xiamin Zhu.

Abbreviations:

BCMA B-cell maturation antigen

BCMA-UCART B-cell maturation antigen-targeted universal chimeric antigen receptor T-cell

CAR-T chimeric antigen receptor T

CRS cytokine release syndrome

GVHD graft-versus-host disease

ICANS immune effector cell-associated neurotoxicity syndrome

MM multiple myeloma

TCR T cell receptor

The author certifies that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. Furthermore, the author certifies that this material or similar material has not been and will not be submitted to or published in any other publications.

The authors declare that they have no conflicts of interest.

This study was supported by 2022 hospital-level project of the First Affiliated Hospital of Soochow University (HLYJ-2022-04).

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

How to cite this article: Dai Y, Tang F, Mao Y, He N, Yu M, Zhang M, Gu S, Lu Y, Shang J, Zhu X. Nursing care of patients with relapsed and refractory multiple myeloma treated with B-cell mature antigen-targeted universal chimeric antigen receptor T cells. Medicine 2023;102:47(e36037)
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