Lisocabtagene maraleucel as a second-line treatment for R/R LBCL: PROs from the PILOT study

Results from the phase II PILOT trial (NCT03483103), which were previously covered by the Lymphoma Hub, demonstrated the effectiveness of lisocabtagene maraleucel (liso-cel) as a second-line therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) not intended for hematopoietic stem cell transplantation.¹ Briefly, liso-cel was associated with an overall response rate and complete response rate of 80% and 54%, respectively.¹ Results from this trial, in addition to results from the phase III TRANSFORM trial (NCT03575351), led to the approval of liso-cel for patients with R/R LBCL.

Here, we summarize a health-related quality of life (HRQoL) and patient-reported outcomes (PROs) analysis from the PILOT trial, published by Gordon et al.¹ in Haematologica.

Study design and patient population¹

• The study design and patient characteristics were previously reported by the Lymphoma Hub.
• HRQoL was a secondary endpoint, and was assessed using three PRO instruments:
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 items (EORTC QLQ-C30)
  • Functional Assessment of Cancer Therapy-Lymphoma “Additional Concerns” Subscale (FACT-LymS)
  • EuroQoL 5 Dimension 5 Level (EQ-5D-5L).
• PROs were assessed at screening (baseline), before treatment (≤7 days before lymphodepletion), preinfusion on the day of liso-cel infusion (Day 1), after treatment on Days 29, 60, 90, 180, 270, 365, 545, and 730 (end of study), and at disease progression.
  • Final PROs were recorded from patients who discontinued the study early.

Key findings¹

• Of 61 patients included in the study, 56, 49, 55, and 54 were evaluable for the EORTC QLQ-C30, FACT-LymS, EQ-5D-5L health utility index, and EQ-5D-5L visual analog scale measurements, respectively.

HRQoL at baseline

• When compared with reference age and matched general populations, baseline mean HRQoL scores were slightly worse across most domains, with clinically meaningful worse scores in the EORTC QLQ-C30 fatigue, social functioning, and appetite loss domains.

Within-group changes in HRQoL scores

• Following transient worsening at Day 1 or Day 29, improvements in least squares mean HRQoL scores were generally observed for the primary domains of interest.
• Overall least squares mean changes from baseline through Day 545 are shown in Table 1.

Table 1. Overall least squares mean changes from baseline to Day 545*

Domain	Overall least squares mean change (95% CI)	p value
CI, confidence interval; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 items; EQ-5D-5L, EuroQoL 5 Dimension 5 Level; FACT-Lym, Functional Assessment of Cancer Therapy-Lymphoma; FACT-LymS, FACT-Lym “Additional Concerns” Subscale; GH, global health; HUI, health utility index; QoL, quality of life; VAS, visual analog scale. *Adapted from Gordon, et al.1 †An increased score indicates improved QoL/function; for symptom domains, an increased score indicates worsened symptoms. ‡An increased score indicates improved QoL. §An increased score indicates improved QoL.
EORTC QLQ-C30†
GH/QoL	2.77 (−0.36 to 5.91)	0.082
Physical functioning	−1.67 (−4.88 to 1.53)	0.298
Role functioning	−3.21 (−8.01 to 1.60)	0.187
Cognitive functioning	−0.55 (−3.50 to 2.41)	0.711
Fatigue	−6.94 (−10.34 to −3.55)	<0.001
Pain	−4.12 (−7.62 to −0.62)	0.022
Emotional functioning	2.47 (−0.36 to 5.30)	0.086
Social functioning	−2.39 (−7.60 to 2.81)	0.362
Nausea/vomiting	1.25 (−0.96 to 3.47)	0.262
Dyspnea	0.99 (−2.61 to 4.59)	0.585
Insomnia	0.76 (−3.77 to 5.29)	0.740
Appetite loss	−5.66 (−9.84 to −1.47)	0.009
Constipation	−1.30 (−4.39 to 1.79)	0.402
Diarrhea	−2.92 (−6.53 to 0.70)	0.111
Financial difficulties	1.27 (−2.72 to 5.26)	0.526
FACT-Lym‡
FACT-LymS	4.08 (2.55 to 5.61)	<0.001
EQ-5D-5L§
EQ-5D-5L HUI	0.02 (−0.02 to 0.06)	0.341
EQ-VAS	4.35 (1.27 to 7.43)	0.006

Within-patient changes in HRQoL scores

• Most patients showed an improvement or no change in EORTC QLQ-C30 primary domains of interest and FACT-LymS scores from baseline throughout treatment (Figure 1).

EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 items; FACT-LymS, Functional Assessment of Cancer Therapy-Lymphoma “Additional Concerns” Subscale; GH, global health; QoL, quality of life.
*Adapted from Gordon, et al.¹

 

Key learnings
Treatment with liso-cel showed improved and sustained HRQoL outcomes in patients with R/R LBCL not intended for transplantation. In most patients, liso-cel treatment was associated with a clinically meaningful improvement in EORTC QLQ-C30 fatigue and FACT-LymS scores.