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CARVYKTI®

(ciltacabtagene autoleucel)

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CARVYKTI® (ciltacabtagene autoleucel)

Medical Information

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

Last Updated: 10/01/2025

Summary

  • CARTITUDE-4 (MMY3002) is a phase 3, open-label study evaluating CARVYKTI vs standard care regimens (pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in patients with relapsed and lenalidomide-refractory multiple myeloma (MM) who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and an immunomodulatory drug.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 significant relative gain in the time without grade 3/4 adverse events (AEs) were observed for CARVYKTI vs SOC.

PRODUCT LABELING

CLINICAL DATA - Q-TiWST ANALYSIS

CARTITUDE-4 (MMY3002; NCT04181827) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI vs standard care (PVd or DPd) in patients with lenalidomide-refractory MM after 1-3 prior LOT.1,2

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.

  • 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

Methods

  • 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.3
  • The survival time was divided into the following 3 general, distinct health states:3
    • 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)
  • 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.3
  • 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.3
  • 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,4 a 10% to 15% relative Q-TWiST gain was considered clinically important difference.3

Q-TWiST Formula with Utility Weights Across Health States3

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

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.3
  • Patients receiving CARVYKTI vs SOC showed statistically significant improvement in the time without symptoms or grade 3/4 AEs in the ITT and as-treated populations.3
  • 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.3

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 (3.6-5.1)
2.4 (1.9-3.0)
1.9 (0.9-2.9)
PFS time without grade 3/4 AEs, months
26.2 (23.7-28.6)
15.4 (13.2-17.7)
10.7 (7.5-13.9)
Time after disease progression, months
6.4 (4.8-8.0)
14.3 (12.2-16.5)
-8.0 (-10.6-[-5.3])
Gain in time without symptoms or grade 3/4 AEs, months
31.5 (29.4-33.6)
23.8 (21.9-25.8)
7.7 (4.8-10.5)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

  • The Q-TWiST scores were statistically higher 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.3
  • Patients in the CARVYKTI vs SOC arm experienced a significantly longer duration of PFS without grade 3/4 AEs and grade 1-4 SPMs in both the ITT and as-treated populations.3

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).

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
  • The analysis was based on pre-defined, fixed utility values suggested by Gelber et al (1995).5 Validating the findings with clinical trials or real-world data would strengthen generalizability.3
  • Results are based on a single data cut (May 1, 2024; median follow-up 34 months).3

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 26 September 2025.

 

References

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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 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.  
5 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.