ASH 2018 | Efficacy and safety outcomes of axi-cel in patients with relapsed/refractory large B-cell lymphoma comparable between patients who were aged < 65 years versus ≥ 65 years

On Saturday 1^st December 2018, an oral abstract session took place at the 60^th American Society of Hematology (ASH) Annual Meeting in San Diego, CA. During Session 627 (Aggressive lymphoma - results from retrospective/observational studies: outcomes with CD-19 CAR‑T therapy and checkpoint blockade in the real world setting) Abstract 96 was presented by Dahlia Sano M.D., MD Anderson Cancer Center (MDACC), Houston, TX.

The objective of the study was to compare the safety and efficacy outcomes of patients aged < 65 years versus patients aged ≥ 65 years with relapsed/refractory large B-cell lymphoma and who had been treated with axicabtagene ciloleucel (axi-cel). Data from patients treated with axi-cel between 6/18/2015 and 09/17/2018 at MDACC were retrospectively analyzed and reviewed.

Patient population and baseline characteristics

• A total of 72 patients were included:
  • 52 (72%) patients were < 65 years of age (median age 42 years [range 23–64])
  • 20 (28%) patients were ≥ 65 years of age (median age 68 years [range 65–83])
• Patients had a diagnosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL)
• The majority of patients in both groups were male, ECOG 0–2, Stage III–IV, with DLBCL
• Differences in baseline characteristics identified between the groups included:
  • More patients with a higher IPI score in the older age group. IPI 3–5: 35 (67%) patients in the < 65 years of age group and 17 (85%) patients in the ≥ 65 years group
  • More heavily pre-treated patients in the younger group. Prior lines of therapy ≥ 3: 41 (79%) patients in the < 65 years of age group and 12 (60%) patients in the ≥ 65 years group, P = 0.005

Efficacy results

• Sixty-seven patients were evaluable for efficacy (2 patients < 65 years and 3 patients ≥ 65 years did not have an efficacy evaluation)
• At Day 30, overall response rate (ORR) was 82%
  • ORR of 78% in the < 65 years of age group and 94% in the ≥ 65 years group, P = 0.1678
• At Day 30, complete response (CR) rate was 55%
  • CR rate of 50% in the < 65 years of age group and 71% in the ≥ 65 years group, P = 0.2699
• Estimated median overall survival (OS) was 15.4 months (95% CI, 13.5–NA)

Safety results

• All 72 patients were evaluable for safety
• The majority of cytokine release syndrome (CRS) events were Grade 1–2
  • 40 (77%) patients in the < 65 years group
  • 16 (80%) patients in the ≥ 65 years group
• Grade 3–4 CRS was experienced in 5 (9.6%) patients in the < 65 years group and in 2 (10%) patients in the ≥ 65 years group
• One patient experienced Grade 5 CRS in the ≥ 65 years group
• CAR-related encephalopathy syndrome (CRES):
  • Grade 0: 14 (26.9%) patients in the < 65 years group and in 6 (30%) patients in the ≥ 65 years group
  • Grade 1–2: 7 (15.4%) patients in the < 65 years group and in 5 (25%) patients in the ≥ 65 years group
  • Grade 3–4: 30 (57.7%) patients in the < 65 years group and in 9 (45%) patients in the ≥ 65 years group
  • No Grade 5 CRES.
• Tocilizumab use was similar between the two groups:
  • 33 (64%) patients in the < 65 years group and in 15 (75%) patients in the ≥ 65 years group, P = 0.41
• Steroid use was higher in the younger age group:
  • Twenty-seven (52%) patients in the < 65 years group and 6 (30%) patients in the ≥ 65 years group, P = 0.002
• Median hospital stay was 16 days for patients in both groups (range 7–64 days in the < 65 years group and 10–41 days in the ≥ 65 years group, P = 0.62)
• ICU admission rate was 42% in the < 65 years group and 35% in the ≥ 65 years group, P = 0.38
  • Median ICU stay of 3 days (range 1–30) in the < 65 years group and 4 days (range 2–7) in the ≥ 65 years group

Conclusions

• Response rates and survival were comparable between elderly patients (aged ≥ 65 years) and younger patients (aged < 60 years)
• Safety was comparable between the two age groups in terms of:
  • Incidence and severity of CRS and CRES
  • Tocilizumab usage
  • Length of hospital stay
  • ICU admission rates and duration of stay
• Steroid use was higher in the younger age group likely due to a higher incidence of Grade 3 CRES
• Prospective evaluation in a larger sample size and evaluation of safety in the very elderly population is needed to further confirm these findings