CAR T-cell therapy in older patients: Efficacy and rates of immune-mediated toxicity

Older patients (≥ 65 years) diagnosed with multiple myeloma (MM) are under-represented in clinical trials evaluating anti B-cell maturation antigen-directed chimeric antigen receptor (BCMA CAR) T-cell therapy, and are prone to inferior clinical outcomes due to associated comorbidities and reduced functional reserves.¹

Akhtar et al.¹ published a systematic review and meta-analysis investigating the efficacy of CAR T-cell therapies and rates of associated immune-mediated toxicity in older patients with MM. We summarize the key findings below.

Methods¹

• The review encompassed phase I, II, and III clinical trials and prospective observational studies including patients ≥65 years old with MM or plasma cell leukemia and receiving anti-BCMA CAR T-cell therapy.
• PubMed, Scopus, Web of Science, Ovid, Embase, CENTRAL, and CINAHL databases were screened.
• Case reports, case series, and retrospective studies were excluded.

Key findings¹

• A total of 14 studies were analyzed (N = 558):
  • 3 studies were phase II (n = 287).
  • 10 studies were phase I (n = 266).
  • 1 study was a prospective, observational study (n = 5).
• Overall response rates (ORR) were high in the older patient population (Figure 1) and remained comparable to younger patients <60 years old (86%).

ORR, overall response rate; R-ISS, revised-international staging system.
*Adapted from Akhtar, et al.¹

• Information on cytokine release syndrome (CRS) was available in 335 patients.
  • The pooled CRS rate in older patients was 95%, compared with 91% in younger patients.
  • Grade ≥3 CRS occurred in 21% of older patients vs 20% in younger patients.
• Information on immune cell-associated neurotoxicity syndrome (ICANS) was available in 316 patients.
  • The pooled rate of ICANS in older patients was 15% compared with 6% in younger patients.
  • Pooled rates of Grade ≥3 ICANS were comparable between older and younger patients, at 1% and 0%, respectively.

Key learnings

ORR and rates of CRS were comparable between younger and older patients. There were increased rates of ICANS in older vs younger patients, and further studies are warranted to understand the etiology and associated risk factors. Results from this analysis show that age should not be used as an exclusionary criterion from future clinical trials or from receiving anti-BCMA CAR T-cell therapy in real-world settings.