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%).

Figure 1. Pooled ORR in older patients treated with anti-BCMA CAR T-cell therapy* 

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.