Chimeric antigen receptor (CAR) T cell therapy is a vital tool in the treatment of cancer, and it has revolutionized the landscape of relapsed or refractory DLBCL. However, retrospective reviews have shown that CAR-T therapy is associated with adverse effects such as the development of myelodysplastic syndromes (MDS) and clonal cytopenias of undetermined significance (CCUS).

Development of CCUS and MDS

“Clonal cytopenia of unknown significance (CCUS) is characterized by a low blood count without an apparent cause, as well as a portion of blood cells that carry an acquired genetic mutation. Individuals with these genetic mutations have a 75% chance of developing myelodysplastic syndromes (MDS) or a related condition within four to five years, and low blood counts alone can have negative consequences.”

A recent study of 4 patients with diffuse large B-cell lymphoma (DLBCL) who had received CAR-T therapy, showed the following:

• 2 patients developed CCUS within 2 months
• 1 patient developed MDS within 10 months
• 1 patient developed MDS within 26 months

Each patient had a complete response after the initial completion of the CAR-T therapy.

Risk Factors and Treatment

This study indicated several risk factors for developing CCUS or MDS after CAR-T therapy:

• Advanced age
• Prior chemotherapies and radiation exposure
• A prior stem-cell transplant: this is because the bone marrow does not receive an appropriate amount of time to recover before CAR-T therapy begins
• Lymphodepleting therapies

Treatment for CCUS is not required, and close follow-up is recommended for patients who develop MDS. “Recognizing patients with MDS/CCUS mutations before CAR-T cell therapy can aid in the prediction of the development of these disorders post-CAR-T cell therapy.” CCUS patients have a higher risk of developing MDS.

Despite the risk of developing CCUS or MDS, CAR-T therapy remains a promising and highly effective treatment for relapsed or refractory DLBCL patients. This therapy can help achieve a sustained and positive response. “Emergence of this form of adoptive immunotherapy has resulted in improved response rates in relapsed and refractory B-cell malignancies.”

Monitoring and follow-up care needs to be a priority. Side effects after CAR-T therapy are common, although most effects will be brief and respond well to treatment. Watch for any long-lasting conditions of CCUS or MDS, such as: fatigue, shortness of breath, very low white blood cell counts, bruising or bleeding and bone pain.

Conclusion

“Long-term follow-up of patients receiving CAR-T cell therapy is necessary to monitor for incidence of MDS/CCUS, especially in prolonged cytopenic patients. Further investigations need to be undertaken to establish a connection between CAR-T cell therapy and MDS/CCUS to allow timely management of these patients before they progress to AML.”