The development of myelitis during Atezolizumab therapy.
MRI of the patient's cervical spine after atezolizumab therapy. MRI scans show signs of myelitis.
MRI of the patient's cervical spine after atezolizumab therapy. MRI scans show signs of myelitis.
MRI of the patient's cervical spine after atezolizumab therapy. MRI scans show signs of myelitis.
First and foremost, it is important to emphasize: The development of myelitis (inflammation of the spinal cord) during therapy with atezolizumab (Tecentriq) is a known, but rare, immune-mediated adverse event (irAE).
Atezolizumab
is a monoclonal antibody, an immune checkpoint inhibitor (anti-PD-L1).
Its main goal is to "release the brakes" on the immune system so it can
attack the tumor. However, this activation can lead to immune cells
attacking healthy tissues, including the nervous system. Myelitis is one
of the most serious neurological complications.
is a monoclonal antibody, an immune checkpoint inhibitor (anti-PD-L1).
Its main goal is to "release the brakes" on the immune system so it can
attack the tumor. However, this activation can lead to immune cells
attacking healthy tissues, including the nervous system. Myelitis is one
of the most serious neurological complications.
Key Aspects of Myelitis Development Following Atezolizumab Therapy:
- Mechanism of Development: This is not a direct toxic effect of chemotherapy, but an immune-mediated
complication. Atezolizumab blocks the PD-1/PD-L1 signaling pathway,
which is necessary for maintaining immune tolerance. As a result,
autoreactive T-lymphocytes can become activated and attack the myelin
sheath of nerve fibers in the spinal cord. Polychemotherapy administered
concurrently with atezolizumab may further modulate the immune
response, potentially increasing the risk or influencing the course of
irAEs. - Frequency: Myelitis is classified as a rare
complication (frequency < 1%). According to data from clinical
trials and post-marketing surveillance, among all irAEs associated with
PD-1/PD-L1 inhibitors, neurological complications occur in less than 1%
of patients, and myelitis is even rarer. However, its consequences can
be severe, so clinicians maintain a high index of suspicion. - Clinical Presentation and Diagnosis:Symptoms: Can develop acutely or subacutely. They include:Sensory
disturbances: numbness, paresthesias (tingling, "pins and needles"),
decreased sensation, often with a sensory "level" on the trunk.Motor disturbances: weakness in the limbs (paresis, paralysis).Autonomic dysfunction: urinary or fecal incontinence or retention.Radicular pain, back pain.Diagnosis: MRI of the spinal cord with contrast enhancement
plays a key role. It typically reveals focal or multisegmental
hyperintense signal on T2-weighted images, often with contrast
enhancement. Also performed:Lumbar
puncture for cerebrospinal fluid (CSF) analysis (may reveal
lymphocytosis, elevated protein, oligoclonal bands, but sometimes CSF
can be normal).Exclusion of other causes: spinal metastases, infectious myelitis (e.g., caused by herpes viruses), paraneoplastic syndrome. - Influence of Polychemotherapy:
The combination of atezolizumab with chemotherapy (e.g., in treatment
regimens for lung cancer, triple-negative breast cancer, or small cell
lung cancer) does not eliminate the risk of myelitis. Moreover, there
are hypotheses that chemotherapy, by damaging tissues, may release
additional antigens and potentially enhance autoimmune reactions.
However, no clear proven difference in the frequency of myelitis between
atezolizumab monotherapy and its combination with chemotherapy has been
established. - Treatment: Requires immediate intervention.1st Line: High-dose corticosteroids (pulse therapy with methylprednisolone 1-2 g/day IV for 3-5 days).If insufficiently effective: Second-line therapy is added — plasmapheresis or intravenous immunoglobulin (IVIG). In resistant cases, rituximab or cyclophosphamide may be used.Temporary or permanent discontinuation of atezolizumab is mandatory.
The decision to resume immunotherapy is made individually, taking into
account the severity of the complication and oncological necessity. - Prognosis:
Depends on the timeliness of diagnosis and treatment initiation. With
early and aggressive treatment, complete or partial functional recovery
is possible. However, in severe cases, persistent neurological deficits
(paresis, sensory disturbances, bladder dysfunction) may remain.
Practical Recommendations for Patients and Physicians:
- For patients: Immediately inform the treating physician of any new neurological symptoms (numbness, limb weakness, problems with urination). Do not attribute these symptoms to fatigue or the effects of chemotherapy.
- For physicians:
Maintain a high index of suspicion for neurological irAEs. If myelitis
is suspected, urgent consultation with a neurologist and an MRI of the
spinal cord are necessary.
Conclusion: Myelitis is a rare but severe immune-mediated complication
of atezolizumab therapy (both as monotherapy and in combination with
polychemotherapy). Its development is caused by the activation of
autoimmune reactions against the spinal cord. The key to minimizing
consequences is early recognition, discontinuation of immunotherapy, and
immediate initiation of immunosuppressive treatment.
of atezolizumab therapy (both as monotherapy and in combination with
polychemotherapy). Its development is caused by the activation of
autoimmune reactions against the spinal cord. The key to minimizing
consequences is early recognition, discontinuation of immunotherapy, and
immediate initiation of immunosuppressive treatment.