(PA-019) Factors Associated with Response, Neurotoxicity, and Survival in Patients with Multiple Myeloma Treated with Chimeric Antigen Receptor T-cell (CAR-T) Therapy

Chimeric Antigen Receptor T-cell (CAR-T) therapy is emerging as a standard treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its associated side effects can be disabling and reliable predictive factors for responses and toxicities remain unclear.

Methods:

A retrospective study of RRMM patients who received Ide-cel or Cilta-cel at our institution between 2021–2025 was conducted to identify factors associated with duration of response (DoR), neurotoxicity (NT), cytokine release syndrome (CRS), and overall survival (OS).

Results:

A total of 93 patients who received Ide-cel (24/93), or Cilta-cel (59/93) were included in this study. The median age at the time of CAR-T therapy infusion was 66 years (range: 35–83). 45/77 patients (58.4%) had high-risk cytogenetics. Patients received a median of 4 prior lines (range: 0–22) and 42% had progressive disease at the time of CAR-T infusion. 

Among the 93 patients, 72 (77.4%) developed some grade of CRS (G1–G2: 68/72, 94.4%), while 15 (16.1%) experienced NT. The median onset of NT was 13 days, with 7 patients (7.5%) presenting with delayed NT, including cranial nerve palsies and strokes, after day 15.

An increase of ≥50% from baseline ferritin (P = 0.0008) or C-reactive protein (CRP) (P = 0.04), and a peak absolute lymphocyte count (ALC) >1 x 10⁹/L (P < 0.0001) were associated with CRS. High MM stage (P = 0.026), peak ferritin >400 ng/mL (P = 0.004), and peak ALC >1 x10⁹/L (P = 0.046) were linked to the development of NT, while type of product (P = 0.04) and ≤ 3 prior lines (P = 0.07) to the severity of NT. Elevated IL-6 and IL-8 levels were detected in the serum or cerebrospinal fluid of patients with severe NT.

Median follow-up was 8.5 months. The overall response rate (ORR), including partial responses or better, was 92.5%. Ide-cel therapy, poor pre-CAR-T response, and absence of CRS were associated with inferior ORR. 12/58 evaluable patients (21%) experienced progression within 6 months of infusion. The median DoR was 25.3 months (95% CI: 14.2-36.2). Variables influencing DoR included type of product (P = 0.003), pre-CAR-T response (P = 0.008), age >60 years (P = 0.02), number of prior lines (P = 0.07), onset of CRS (P < 0.001), baseline ferritin >200 ng/mL (P = 0.012), peak ferritin > 400 ng/mL (P = 0.018), CRP increase of >50% (P = 0.008), peak ALC >3 x10⁹/L (P = 0.06), and soluble C5b9 >250 ng/mL (P = 0.08).

The median OS was 38.7 months, with 3-month and 9-month OS estimates of 97% and 62%, respectively. Factors associated with OS included peak ALC >1 x10⁹/L (P = 0.09), peak AMC >0.3 x10⁹/L (P = 0.02), and C5b9 >250 ng/mL (P = 0.09).

Conclusions:

Patients with NT had higher ferritin, peak ALC, and cytokine levels. While peak ALC was associated with NT, it also correlated with longer DoR and OS. Steroid prevention has been suggested to reduce delayed NT, but since peak ALC alone may not be a definitive biomarker, a collaborative effort is needed to evaluate toxicity risks while balancing clinical responses.