Management and Response Assessment of Chimeric Antigen Receptor T-Cell Therapy in Clinical Practice for Relapsed and Refractory Multiple Myeloma
Key Points
- 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.
- Unmet Need: Despite therapeutic advancements, resistance to treatment remains a significant challenge, leading to poor prognosis for many patients with highly refractory disease.
- 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.
- 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.
- 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.
- 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.
- 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.
- CAR T-cell therapy has shown promise in patients with relapsed and refractory multiple myeloma, with high response rates and extended overall survival.
- Three BCMA-targeted CAR T-cell therapies have been approved: ide-cel, cilta-cel, and eque-cel.
- Infection screening is essential before initiating CAR T-cell therapy, including evaluation for viral infections, hepatitis, and reactivation of cytomegalovirus and Epstein-Barr virus.
- 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.
- 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.
- Antimicrobial prophylaxis and immunoglobulin replacement may be considered to prevent infections and manage hypogammaglobulinemia.
- Vaccination strategies for patients undergoing CAR T-cell therapy are still being studied, and live vaccines should be avoided.
- 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.
- Haematological toxicity, including cytopenias, is common with CAR T-cell therapy and requires aggressive supportive care and close monitoring of blood counts.
- Referral logistics should prioritize early referral and consider disparities in patient access to care.
- 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.
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Overview
Title
Management and Response Assessment of Chimeric Antigen Receptor T-Cell Therapy in Clinical Practice for Relapsed and Refractory Multiple Myeloma
Authoring Organization
International Myeloma Working Group
Publication Month/Year
May 28, 2024
Last Updated Month/Year
May 31, 2024
Document Type
Guideline
Country of Publication
Global
Document Objectives
Chimeric antigen receptor (CAR) T-cell therapy has shown promise in patients with late-line refractory multiple myeloma, with response rates ranging from 73 to 98%. To date, three products have been approved: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which are approved by the US Food and Drug Administration, the European Medicines Agency, Health Canada (ide-cel only), and Brazil ANVISA (cilta-cel only); and equecabtagene autoleucel (eque-cel), which was approved by the Chinese National Medical Products Administration. CAR T-cell therapy is different from previous anti-myeloma therapeutics with unique toxic effects that require distinct mitigation strategies. Thus, a panel of experts from the International Myeloma Working Group was assembled to provide guidance for clinical use of CAR T-cell therapy in myeloma. This consensus opinion is from experts in the field of haematopoietic cell transplantation, cell therapy, and multiple myeloma therapeutics.
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory, Outpatient, Radiology services
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment, Management
Diseases/Conditions (MeSH)
D009101 - Multiple Myeloma, D000076962 - Receptors, Chimeric Antigen
Keywords
multiple myeloma, CAR-T, Chimeric Antigen Receptor T-Cell Therapy
Source Citation
Yi Lin, Lugui Qiu, Saad Usmani, Chng Wee Joo, Luciano Costa, Benjamin Derman, Juan Du, Hermann Einsele, Carlos Fernandez de Larrea, Roman Hajek, P Joy Ho, Efstathios Kastritis, Joaquin Martinez-Lopez, Maria-Victoria Mateos, Joseph Mikhael, Philippe Moreau, Chandramouli Nagarajan, Ajay Nooka, Michael O'Dwyer, Fredrik Schjesvold, Surbhi Sidana, Niels WCJ van de Donk, Katja Weisel, Sonja Zweegman, Noopur Raje, Paula Rodriguez Otero, Larry D Anderson, Shaji Kumar, Tom Martin, Consensus guidelines and recommendations for the management and response assessment of chimeric antigen receptor T-cell therapy in clinical practice for relapsed and refractory multiple myeloma: a report from the International Myeloma Working Group Immunotherapy Committee, The Lancet Oncology, 2024, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(24)00094-9.