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(ciltacabtagene autoleucel)

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CARVYKTI® (ciltacabtagene autoleucel)
Medical Information

CARVYKTI – Quality-Adjusted Time Without Symptoms or Toxicity Analysis (Q-TWiST)

Last Updated: 09/01/2026

Summary

  • CARTITUDE-4 is a phase 3, open-label, multicenter study evaluating CARVYKTI vs standard care regimens, DARZALEX FASPRO (daratumumab and hyaluronidase), pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd), in patients with relapsed/refractory multiple myeloma (RRMM) who received 1-3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory drug, and are refractory to lenalidomide.1,2
    • Sidana et al (2025)3 presented quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis results that evaluated the comprehensive benefit-risk profile of CARVYKTI vs standard of care (SOC) using data from the CARTITUDE-4 clinical study, with a maximum follow-up of 45 months. A longer progression-free survival (PFS) and relative gain in the time without grade 3/4 adverse events (AEs) were observed for CARVYKTI vs SOC.
      • Sidana et al (2025)4 presented results from a focused Q-TWiST analysis of the CARTITUDE-4 study evaluating the impact of grade 3/4 neurologic AEs on the quality-adjusted survival for CARVYKTI vs SOC, with a maximum follow-up of 45 months. A longer duration of PFS without grade 3/4 neurologic AEs and improvements in Q-TWiST outcomes were reported for CARVYKTI vs SOC.

PRODUCT LABELING

CLINICAL DATA - Q-TWiST ANALYSIS

CARTITUDE-4 (NCT04181827) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of DPd or PVd) in adult patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior LOTs.1,2

Q-TWiST is a validated method comprehensively integrating progression, survival, treatment toxicities, and patient quality of life into a single metric to evaluate overall treatment effect.3,4

Methods

  • Q-TWiST analysis: overall grade 3/4 AEs3
    • As of the data cutoff date of May 1, 2024, the Q-TWiST analysis included intention-to-treat (ITT) populations (CARVYKTI, N=208; SOC, N=211) and as-treated populations (CARVYKTI, N=176; SOC, N=211) from the CARTITUDE-4 study.
    • The survival time was divided into the following 3 general, distinct health states:
      • PFS time without symptoms or grade 3/4 AEs (TWiST)
      • PFS time with symptoms and grade 3/4 AEs (TOX)
      • Time after disease progression (REL)
  • Q-TWiST analysis: grade 3/4 neurologic AEs4
    • As of the data cutoff date of May 1, 2024, the Q-TWiST analysis included intention-to-treat (ITT) populations (CARVYKTI, N=208; SOC, N=211) and as-treated populations (CARVYKTI, N=176; SOC, N=208) from the CARTITUDE-4 study.
    • The overall survival (OS) was divided into the following 3 distinct health states:
      • PFS time without grade 3/4 neurologic AEs (TWiST)
      • PFS time with grade 3/4 neurologic AEs (TOX)
      • Time after disease progression (REL)
  • Conventional utility weights used for each health state - TWiST (1.0), TOX (0.5), and REL (0.5) are presented in Figure: Q-TWiST Formula with Utility Weights Across Health States.
  • A base case analysis was conducted in the ITT and as-treated populations and used grade 3/4 (treatment-emergent and non-treatment-emergent) AEs and neurologic AEs, including chimeric antigen receptor T-cell (CAR-T)-related events, such as immune effector cell-associated neurotoxicity syndrome (ICANS) and ICANS-associated symptoms.3,4
    • In the CARVYKTI arm, a subanalysis evaluated PFS time with grade 3/4 CAR-T-related neurologic AEs excluding ICANS and ICANS-associated symptoms.4
  • A sensitivity analysis was repeated in the ITT and as-treated populations using an alternative AE definition that included grade 1-4 secondary primary malignancies (SPMs).3
  • As per previous recommendations,5 a 10% to 15% relative Q-TWiST gain was considered clinically important difference.3

Q-TWiST Formula with Utility Weights Across Health States3,4

Abbreviations: REL, time after disease progression; TOX, PFS time with symptoms and grade 3/4 AEs; Q-TWiST, quality-adjusted time without symptoms or toxicity; TWiST, PFS time without symptoms or grade 3/4 AEs; U, utility value assigned to each health state.

Results

Q-TWiST Analysis: Overall Grade 3/4 AEs

Sidana et al (2025)3 presented Q-TWiST analysis results that evaluated the comprehensive benefit-risk profile of CARVYKTI vs SOC using data from the CARTITUDE-4 clinical study, with a maximum follow-up of 45 months.

Base Case Analysis
  • At a median follow-up of 34 months, the mean PFS time without grade 3/4 AEs in the CARVYKTI vs SOC arm was 26.2 months vs 15.4 months.
  • Patients receiving CARVYKTI vs SOC showed improvement in the time without symptoms or grade 3/4 AEs in the ITT and as-treated populations.
  • A longer duration of PFS without grade 3/4 AEs was experienced in the CARVYKTI vs SOC arm. See Figure: Survival Curves by Q-TWiST Health States.

Q-TWiST Scores in the Base Casea,3
ITT Population
As-treated Population
CARVYKTI (n=208)
SOC
(n=211)
CARVYKTI (n=176)
SOC
(n=211)
Q-TWiST score, months
31.5
23.8
35.6
23.8
Relative gain in time without symptoms or toxicity, months (95% CI)
+7.7 (4.8-10.5)
P<0.001
+11.7 (9.1-14.3)
P<0.001
Relative survival gainb,c, %
+32.1
+49.2
Abbreviations: AE, adverse event; CI, confidence interval; ITT, intention-to-treat; PFS, progression-free survival; Q-TWiST, quality-adjusted time without symptoms or toxicity; SOC, standard of care; TWiST, PFS time without symptoms or grade 3/4 AEs.
aBase case includes grade 3/4 AEs (both treatment-emergent and non-treatment-emergent).
bRelative gain reflects the percentage increase in PFS time without symptoms or toxicity with CARVYKTI vs SOC.
cP<0.001.
Note: Utility weights applied were 1.0 for TWiST and 0.5 for both PFS time with symptoms and grade 3/4 AEs (TOX) and time after disease progression (REL).

Base Case Outcomes Across Q-TWiST Health States in the ITT Population3
CARVYKTI
(n=208)
SOC
(n=211)
CARVYKTI vs SOC
Restricted Mean
(95% CI)
Restricted Mean
(95% CI)
Restricted Mean
(95% CI)
PFS time with grade 3/4 AEs, months
4.3
(3.6 to 5.1)
2.4
(1.9 to 3.0)
1.9
(0.9 to 2.9)
PFS time without grade 3/4 AEs, months
26.2
(23.7 to 28.6)
15.4
(13.2 to 17.7)
10.7
(7.5 to 13.9)
Time after disease progression, months
6.4
(4.8 to 8.0)
14.3
(12.2 to 16.5)
-8.0
(-10.6 to -5.3)
Gain in time without symptoms or grade 3/4 AEs, months
31.5
(29.4 to 33.6)
23.8
(21.9 to 25.8)
7.7
(4.8 to 10.5)a
Abbreviations: AE, adverse event; CI, confidence interval; ITT, intention-to-treat; PFS, progression-free survival; Q-TWiST, quality-adjusted time without symptoms or toxicity; SOC, standard of care; TWiST, PFS time without symptoms or grade 3/4 AEs.
aP<0.001.
Note: Base case includes grade 3/4 AEs (both treatment-emergent and non-treatment-emergent). Utility weights applied were 1.0 for TWiST and 0.5 for both PFS time with symptoms and grade 3/4 AEs (TOX) and time after disease progression (REL).

Survival Curves by Q-TWiST Health States3

A red and grey curved objects AI-generated content may be incorrect.

Abbreviations: AE, adverse event; cilta-cel, ciltacabtagene autoleucel; ITT, intention-to-treat; PFS, progression-free survival; Q-TWiST, quality-adjusted time without symptoms or toxicity; SOC, standard of care.
Note: ITT and as-treated populations included grade 3/4 AEs (both treatment-emergent and non-treatment-emergent).

Sensitivity Analysis
  • Higher Q-TWiST scores were observed in most cases in the CARVYKTI vs SOC arm for utility values of TOX and REL in the sensitivity analysis over a maximum follow-up of 45 months. See Figure: Q-TWiST Estimates for Utility Values of TOX and REL in the Sensitivity Analysis.
  • Patients in the CARVYKTI vs SOC arm experienced a longer duration of PFS without grade 3/4 AEs and grade 1-4 SPMs in both the ITT and as-treated populations.

Q-TWiST Estimates for Utility Values of TOX and REL in the Sensitivity Analysisa,3

A screenshot of a computer

Abbreviations: cilta-cel, ciltacabtagene autoleucel; Q-TWiST, quality-adjusted time without symptoms or toxicity analysis; REL, time after disease progression; SOC, standard of care; TOX, PFS time with symptoms and grade 3/4 AEs.
aNumbers shown are Q-TWiST gain over follow-up time of 45 months in the ITT population.


Q-TWiST Scores on the Sensitivity Scale3
ITT Population
As-treated Population
CARVYKTI
(n=208)
SOC
(n=211)
CARVYKTI
(n=176)
SOC
(n=211)
Q-TWiST score, months
31.4
23.8
35.4
23.8
Relative gain in time without grade 3/4 AEs and grade 1-4 SPMs, months
+7.6
P<0.001
+11.6
P<0.001
Relative survival gaina, %
+32.0
+48.9
Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; ITT, intention-to-treat; PFS, progression-free survival; Q-TWiST, quality-adjusted time without symptoms or toxicity analysis; SOC, standard of care; SPM, second primary malignancy; TWiST, PFS time without symptoms or grade 3/4 AEs.
bRelative gain reflects the percentage increase in PFS time without symptoms or toxicity with CARVYKTI vs SOC.
Note: Utility weights applied were 1.0 for TWiST and 0.5 for both PFS time with symptoms and grade 3/4 AEs (TOX) and time after disease progression (REL).

Q-TWiST Analysis: Grade 3/4 Neurologic AEs

Sidana et al (2025)4 presented results from a focused Q-TWiST analysis of the CARTITUDE-4 study evaluating the impact of grade 3/4 neurologic AEs on the quality-adjusted survival of CARVYKTI vs SOC, with a maximum follow-up of 45 months.

Base Case Analysis
  • The proportion of time spent progression free and free from grade 3/4 neurologic AEs was greater with CARVYKTI than with SOC.
    • In the CARVYKTI arm, evaluation of grade 3/4 CAR-T-related neurologic AEs (TOX2) within the broader grade 3/4 neurologic AE profile (TOX1) showed that the duration of CAR-T-related neurologic AEs, excluding ICANS and ICANS-associated symptoms, was short relative to the overall duration of grade 3/4 neurologic AEs.
  • CARVYKTI was associated with a longer duration of PFS without grade 3/4 neurologic AEs than SOC across both the ITT and as-treated populations, see Tables: Q-TWiST Scores in the Base Case and Quality-Adjusted Estimates for TOX, TWiST, and REL in the ITT and As-treated Populations.
  • Across all tested scenarios, Q-TWiST remained higher with CARVYKTI vs SOC, including analyses evaluating the full range of utility values (0-1) for TOX and REL health states over a maximum follow-up of 45 months.

Q-TWiST Scores in the Base Case4
ITT Population
As-treated Population
CARVYKTI
(n=208)
SOC
(n=211)
CARVYKTI
(n=176)
SOC
(n=208)
Q-TWiST score, months
33.6
25.0
38.0
25.1
Relative gain in time without symptoms or toxicity, months (95% CI)
+8.7 (5.7-11.6
P<0.001
+13.1 (10.4-15.7)
P<0.001
Relative Q-TWiST gain,a,b %
+34.6
+52.3
Abbreviations: AE, adverse event; CI, confidence interval; ITT, intention-to-treat; PFS, progression-free survival; Q-TWiST, quality-adjusted time without symptoms or toxicity; REL, time after disease progression; SOC, standard of care; TOX, PFS time with grade 3/4 neurologic AEs; TWiST, PFS time without grade 3/4 neurologic AEs.
aRelative gain reflects the percentage increase in Q-TWiST value with CARVYKTI vs SOC.
bP<0.001.
Note: Utility weights applied were 1.0 for TWiST and 0.5 for both TOX and REL.

Quality-Adjusted Estimates for TOX, TWiST, and REL in the ITT and As-treated Populations4
CARVYKTI
SOC
CARVYKTI vs SOC
Restricted Mean
(95% CI)
Restricted Mean
(95% CI)
Restricted Mean
(95% CI)
P Value
ITT population
   PFS time with grade 3/4
   neurologic AEs, months
0.07
(0 to 0.13)
0.15
(0.04 to 0.26)
-0.09
(-0.21 to 0.04)
0.169
   PFS time without grade 3/4
   neurologic AEs, months
30.4
(28.0 to 32.9)
17.7
(15.4 to 20.1)
12.7
(9.4 to 16.0)
<0.001
   Time after disease progression,
   months
6.4
(4.8 to 8.0)
14.3
(12.2 to 16.5)
-8.0
(-10.6 to -5.3)
<0.001
   Q-TWiST, months
33.6
(31.5 to 35.8)
25.0
(22.9 to 27.0)
8.7 (5.7 to 11.6)
<0.001
As-treated population
   PFS time with grade 3/4
   neurologic AEs, months
0.07
(0 to 0.14)
0.16
(0.04 to 0.28)
-0.08
(-0.23 to 0.06)
0.243
   PFS time without grade 3/4
   neurologic AEs, months
35.7
(33.6 to 37.7)
17.7
(15.4 to 20.1)
17.9
(14.9 to 21.0)
<0.001
   Time after disease progression,
   months
4.7
(3.3 to 6.0)
14.3
(12.2 to 16.5)
-9.7
(-12.2 to -7.1)
<0.001
   Q-TWiST, months
38.0
(36.3 to 39.8)
25.0
(23.0 to 27.0)
13.1
(10.4 to 15.7)
<0.001
Abbreviations: AE, adverse event; CI, confidence interval; ITT, intention-to-treat; PFS, progression-free survival; Q-TWiST, quality-adjusted time without symptoms or toxicity; REL, time after disease progression; SOC, standard of care; TOX, progression-free survival time with grade 3/4 neurologic adverse events; TWiST, progression-free survival time without grade 3/4 neurologic adverse events.
Note: Utility weights applied were 1.0 for TWiST and 0.5 for both TOX and REL. Base case includes grade 3/4 neurologic AEs (both treatment-emergent and non-treatment-emergent).

Strengths and Limitations

  • One major limitation is assuming that all grade 3/4 AEs affect quality of life equally. This issue could be improved by redefining the TOX state to focus on specific AEs that are known to impact quality of life.3,4
  • Q-TWiST analysis evaluated neurologic AEs to assess their contribution to the overall benefit-risk profile of CARVYKTI and to address physician and patient concerns regarding neurologic risks associated with CAR-T therapies.6
  • The analysis was based on pre-defined, fixed utility values suggested by Gelber et al (1995).7 Validating the findings with clinical trials or real-world data would strengthen generalizability.3,4
  • Results are based on the May 1, 2024 data cut, with a median follow-up of 34 months for the overall Q-TWiST analysis and maximum follow-up of 45 months for the neurologic AE-focused analysis.3,4

LITERATURE SEARCH

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 21 August 2026.

 

References

Show
1 San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347.  
2 Sidiqi MH, Corradini P, Purtill D, et al. Efficacy and safety in patients with lenalidomide-refractory multiple myeloma and 1-3 prior lines who received a single infusion of ciltacabtagene autoleucel as study treatment in the phase 3 CARTITUDE-4 trial. Poster presented at: 65th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA.  
3 Sidana S, Shune L, Costa L, et al. Quality-adjusted survival analysis of cilta-cel vs standard of care in lenalidomide-refractory multiple myeloma patients who received 1–3 prior lines of therapy: CARTITUDE-4 trial population. Poster presented at: International Myeloma Society (IMS) Annual Meeting; September 17-20, 2025; Toronto, Canada.  
4 Sidana S, Shune L, Costa L, et al. Quality-adjusted survival analysis of neurologic events with ciltacabtagene autoleucel (cilta-cel) vs standard of care (SOC) in patients (pts) with lenalidomide-refractory multiple myeloma (MM) who received 1-3 prior lines of therapy (LOT): CARTITUDE-4 trial population (pop). Poster presented at: the 67th American Society of Hematology (ASH) Annual Meeting; December 6-9, 2025; Orlando, FL.  
5 Revicki DA, Feeny D, Hunt TL, et al. Analyzing oncology clinical trial data using the Q-TWiST method: clinical importance and sources for health state preference data. Qual Life Res. 2006;15(3):411-423.  
6 Cohen AD, Parekh S, Santomasso BD, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 2022;12(2):32.  
7 Gelber RD, Cole BF, Gelber S, et al. Comparing treatments using quality-adjusted survival: the Q-TWiST method. Am Stat. 1995;49(2):161-169.  

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