Management and Response Assessment of Chimeric Antigen Receptor T-Cell Therapy in Clinical Practice for Relapsed and Refractory Multiple Myeloma

Publication Date: May 28, 2024
Last Updated: May 31, 2024

Key Points

  1. Epidemiology and Treatment Landscape: Approximately 176,404 new cases of multiple myeloma and 117,077 myeloma-related fatalities were estimated globally in 2020. Advances in treatment, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, have significantly improved patient survival.
  2. Unmet Need: Despite therapeutic advancements, resistance to treatment remains a significant challenge, leading to poor prognosis for many patients with highly refractory disease.
  3. Novel Immunotherapies: CAR T-cell therapies targeting BCMA have shown high objective response rates and extended median overall survival in relapsed or refractory multiple myeloma patients.
  4. Clinical Trials: Large randomized trials, such as KarMMa-3 and CARTITUDE 4, have demonstrated the superiority of CAR T-cell therapy over standard triplet therapy in terms of overall response rate and progression-free survival.
  5. Toxicity Management: Optimized management of unique toxic effects associated with CAR T-cell therapy is crucial for its widespread implementation. Deaths from all-cause adverse events were higher in the CAR T group, emphasizing the importance of tailored toxicity management strategies.
  6. Patient Selection: Regulatory approvals vary between regions, with the FDA requiring at least four previous lines of therapy for cilta-cel and ide-cel, while the EMA approves them for patients with at least three previous lines. Drug class refractoriness may be more prognostic than the number of therapy lines.
  7. Future Directions: Ongoing clinical trials are exploring the use of CAR T-cell therapy in frontline treatment and investigating allogeneic CAR T-cell options as potential off-the-shelf alternatives. Rapid manufacturing CAR T cells offer a promising strategy to improve patient access to therapy.
  8. CAR T-cell therapy has shown promise in patients with relapsed and refractory multiple myeloma, with high response rates and extended overall survival. ​
  9. Three BCMA-targeted CAR T-cell therapies have been approved: ide-cel, cilta-cel, and eque-cel. ​
  10. Infection screening is essential before initiating CAR T-cell therapy, including evaluation for viral infections, hepatitis, and reactivation of cytomegalovirus and Epstein-Barr virus. ​
  11. Repeat dosing of the same CAR T-cell therapy is not recommended, but CAR T-cell treatment targeting a different antigen or binding domain could be considered. ​
  12. Close monitoring of organ function and comorbidities, such as cardiopulmonary fitness and renal function, is important for eligibility and safety during CAR T-cell therapy. ​
  13. Antimicrobial prophylaxis and immunoglobulin replacement may be considered to prevent infections and manage hypogammaglobulinemia. ​
  14. Vaccination strategies for patients undergoing CAR T-cell therapy are still being studied, and live vaccines should be avoided. ​
  15. Management of toxic effects, such as cytokine release syndrome and immune effector cell-associated neurologic syndrome, should follow regulatory guidelines and consider early intervention and escalation of therapy when necessary. ​
  16. Haematological toxicity, including cytopenias, is common with CAR T-cell therapy and requires aggressive supportive care and close monitoring of blood counts. ​
  17. Referral logistics should prioritize early referral and consider disparities in patient access to care.
  18. The guidelines aim to provide a harmonized approach to the management of CAR T-cell therapy in clinical practice for relapsed and refractory multiple myeloma.



Management and Response Assessment of Chimeric Antigen Receptor T-Cell Therapy in Clinical Practice for Relapsed and Refractory Multiple Myeloma

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