Optimizing AE Management Post CAR T-Cell Therapy in Multiple Myeloma

Meet the experts

In a recent Training Academy segment hosted by CancerNetwork, a panel of experts spoke about the best practices for mitigating adverse effects (AEs) associated with chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma. They reviewed clinical trial data to better understand the incidence and severity of toxicities such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) before discussing multidisciplinary approaches to improving patient outcomes.

Here are their key takeaways:

AE Management Challenges and Infection Mitigation

• Monitoring patients requires coordination within academic centers and collaboration with community oncologists.
  • Patients and caregivers should be educated on long-term AEs, such as peripheral neuropathy and movement disorders. Transporting patients from the community to a treatment center is another challenge.
• Extensive documentation can help manage infection risks post CAR T-cell therapy.
  • Practices can review vaccines and immunizations required within a year of therapy.

ICANS Incidence and Management

• ICANS or neurotoxicity incidence appears to be similar with different therapies.
  • Neurotoxicity occurred in 15% of the KarMMA-3 population.
  • Neurotoxic events affected 20.5% of those in CARDITUDE-4.
• It may be advisable for patients to avoid driving for 60 days following CAR T-cell therapy due to potential neurotoxicity.
  • Long-term symptoms such as cranial nerve VI or VII palsy may occur.
  • Patients should be referred to neurology if these events take place.

Multidisciplinary Strategies and Developing Areas

• Interdepartmental collaboration can bolster supportive care and toxicity management.
  • Social workers, pharmacists, apheresis teams, and others may assist with facilitating CAR T-cell therapy.
• Early referrals are critical for assessing high-risk diseases in patients who may be candidates for CAR T-cell therapy.
  • Adapting treatment strategies for patients depending on the extent of their prior therapy is an ongoing consideration.
  • Long-term AE risks may be different for heavily pretreated patients vs those with only 1 prior line of therapy.

CRS Incidence and Management

• COVID-19 and respiratory infections may be a reference point when explaining the mechanism of CRS to patients.
  • The median time to onset and median duration were 1 day and
    3.5 days, respectively, with idecabtagene vicleucel (Abecma) in the phase 3 KarMMa-3 trial (NCT03651128).¹
  • The median time to onset and median duration were 8 days and 3 days, respectively, with ciltacabtagene autoleucel (Carvykti) in the phase 3 CARTITUDE-4 trial (NCT04181827).²
• Despite a lack of definitive data, steroids may help manage low-grade CRS.
• Individualized bridging therapy may offset CRS symptoms and decrease tumor burden.
  • Triplet therapy, including proteasome inhibitors and immunomodulatory agents, may be suitable.

References

1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614
2. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379