The Critical Role of NTM and Fungal Testing during CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for certain hematological malignancies. However, this progressive therapy is accompanied by significant immunosuppression, which is known to render patients highly susceptible to a spectrum of opportunistic infections. Among these, nontuberculous mycobacteria (NTM) and fungal infections have emerged as particularly significant threats, with potentially devastating consequences. This blog post will delve into the critical importance of NTM and fungal testing during CAR T-cell therapy, supporting the need for early detection, prevention, and management strategies.

Understanding the Link Between CAR T-Cell Therapy and NTM/Fungal Infections

Whereas CAR T-cell therapy involves the genetic modification of a patient's T cells to target and eliminate cancer cells, it has been shown to be highly effective.  The CAR T-cell therapy process profoundly impacts the person’s immune system. The resulting immunosuppressive state, coupled with other factors such as prolonged hospitalization and the use of broad-spectrum antibiotics, creates an ideal environment for opportunistic pathogens like NTM and fungi to thrive.

Fungal infections can manifest in various forms, including invasive candidiasis, aspergillosis, and pneumocystis pneumonia. These infections can rapidly progress, leading to systemic complications, organ failure, and even death.  Nontuberculous mycobacteria are a group of environmental bacteria that can cause pulmonary and disseminated infections, particularly in immunocompromised individuals. CAR T-cell therapy, by its very nature, profoundly suppresses the immune system, creating fertile ground for NTM to proliferate. The combination of factors including prolonged hospitalization, use of broad-spectrum antibiotics, and underlying malignancy further exacerbates the risk of NTM infection.  Early detection and prompt treatment are crucial for improving patient outcomes.

The Challenges of Diagnosing Fungal and NTM Infections during CAR T-Cell Therapy

Fungal and NTM infections can manifest in various forms, ranging from localized to disseminated disease. These infections can rapidly progress, leading to systemic complications, organ failure, and even death. Early detection and prompt antimicrobial treatment are crucial for improving patient outcomes.

Diagnosing fungal and NTM infections in patients undergoing CAR T-cell therapy can be particularly challenging due to several factors:

• Overlapping symptoms: Many symptoms of fungal and NTM infections, such as fever, cough, fatigue, and shortness of breath, are nonspecific and can mimic other complications of CAR T-cell therapy or the underlying malignancy.
• Slow disease progression: Fungal and NTM infections often have an insidious onset and slow progression, making early detection difficult.
• Diagnostic limitations: Traditional diagnostic methods, such as microbiological examinations, sputum cultures and blood cultures, may have limited sensitivity for detecting certain fungal species and NTM’s, especially in early-stage disease.

The Importance of Proactive Fungal and NTM Testing

To address these challenges and improve patient outcomes, proactive fungal l and NTM testing is essential. This involves a combination of risk assessment, clinical evaluation, and diagnostic modalities.

• Risk assessment: Identifying patients at high risk for fungal and NTM infections is crucial. Factors such as the type of malignancy, intensity of immunosuppression, duration of hospitalization, geographic location, and prior exposure to immunosuppressive therapies should be considered.
• Early and frequent monitoring: Regular clinical assessments, including respiratory symptoms, fever, weight changes, and skin examination, should be performed.
• Diagnostic testing: A variety of diagnostic tests can be employed to detect fungal and NTM infections, including:

▫️Sputum cultures: While not highly sensitive, sputum cultures remain an important diagnostic tool for certain fungal and NTM microorganisms.

▫️ Bronchoscopy with bronchoalveolar lavage (BAL): BAL can increase the diagnostic yield for fungal and NTM infections by obtaining a larger sample of respiratory secretions.

▫️Polymerase chain reaction (PCR): PCR-based assays can detect fungal and NTM DNA in respiratory samples and may provide faster results than culture.

▫️Blood cultures: Blood cultures are essential for detecting disseminated fungal and NTM infections.

▫️Fungal cultures: Fungal cultures can be obtained from various specimens, including respiratory samples, blood, and cerebrospinal fluid.

▪️ Galactomannan assay: This test detects a specific component of the Aspergillus cell wall and can be used to monitor for invasive aspergillosis.

▪️Beta-D-glucan assay: This test detects a cell wall component found in many fungal species and can be used as a broad-spectrum screening tool.

▫️Mycobacterial culture: This is the gold standard for diagnosing NTM infections but can be time-consuming.

▫️Imaging studies: Chest X-rays, CT scans, and PET scans can help identify abnormalities suggestive of Fungal and NTM infections.

In addition to early detection, preventive measures such as Strict infection control practices, Prophylactic antimicrobial therapy, and Supportive care are crucial for reducing the risk of fungal and NTM infections in CAR T-cell therapy patients. 

Abet that significant progress has been made in the management of fungal and NTM infections in CAR T-cell therapy patients, several challenges remain. These include the development of more sensitive and specific diagnostic tests, the optimization of prophylactic antimicrobial strategies, and the identification of novel therapeutic approaches.  The period of waiting for NTM or fungal testing results can be a highly stressful and anxiety-inducing experience. This uncertainty can significantly impact a patient's quality of life in various ways: Psychological (as the await an answer on testing), Physical (declines in physical health or exacerbation if symptoms), Socially (financial burden and relationship strains), and Overall Well-being (reduced quality of life and loss of enjoyment).  It's important to note that the impact of waiting for NTM or fungal testing results can vary widely depending on the severity of symptoms, the patient's overall health, and their personal coping mechanisms.

Conclusion

Fungal and NTM infections represent significant threats to patients undergoing CAR T-cell therapy. Proactive testing, coupled with effective prevention and management strategies, is essential for optimizing patient outcomes. By understanding the risk factors, recognizing the challenges of diagnosis, and implementing appropriate testing and prevention measures, healthcare providers can play a crucial role in improving the care of these patients.

Eurofins Viracor offers a breadth of PCR and NGS assays specifically designed to address the limitations of common diagnostic testing and may ease the quality-of-life impact currently experienced by patients awaiting answers.

By utilizing advanced technologies and methodologies, Viracor assists clinicians in patient selection, treatment monitoring, and the early detection of potential complications. This collaborative approach between Eurofins Viracor and healthcare providers contributes to the successful implementation of Fungal and NTM disease testing in patients, ultimately improving the outcomes and quality of life for those impacted by this disease.

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