CARTITUDE-4 Analysis Shows Bridging Therapy Response Predicts Cilta-Cel Benefit in Lenalidomide-Refractory Myeloma

Achievement of at least a partial response (PR) to bridging therapy prior to ciltacabtagene autoleucel (Carvykti; cilta-cel) infusion led to superior 30-month progression-free survival (PFS) and overall survival (OS) outcomes compared with lack of response to bridging therapy in patients with lenalidomide (Revlimid)-refractory multiple myeloma, including those in high- and standard-risk cytogenetic subgroups, according to data from an analysis of the phase 3 CARTITUDE-4 trial (NCT04181827) presented at the 2026 EHA Congress.¹

In the high-risk cytogenetics subgroup, 30-month PFS rates were 65.1% (95% CI, 51.4%-75.8%) for patients with a PR or better following bridging therapy (n = 64) vs 51.2% (95% CI, 35.1%-65.2%) for those with less than a PR with bridging therapy (n = 41). The median PFS was not reached (NR) vs 35.2 months, respectively. The 30-month OS rates were 87.2% (95% CI, 76.1%-93.4%) for bridging therapy responders vs 75.6% (95% CI, 59.4%-86.1%) for non-responders, with median OS that was NR in each group.

In the standard-risk cytogenetics subgroup, 30-month PFS rates were 85.0% (95% CI, 69.6%-93.0%) for those who achieved PR or better with bridging therapy (n = 40) vs 70.2% (95% CI, 40.9%-86.9%) for those who did not respond (n = 19). The 30-month OS rates were 92.5% (95% CI, 78.5%-97.5%) vs 76.6% (95% CI, 44.9%-91.9%), respectively. The median PFS and OS were NR in both groups.

“Cilta-cel demonstrated a profound benefit in patients with high- and standard-risk cytogenetics when multiple myeloma was well controlled at the time of infusion,” Niels WCJ van de Donk, MD, PhD, of the Amsterdam University Medical Center in the Netherlands, and colleagues wrote in a poster presentation of the data.

In April 2024, the FDA approved cilta-cel for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and who are refractory to lenalidomide, based on prior data from CARTITUDE-4.²

How was the CARTITUDE-4 cytogenetic subgroup analysis designed?

The phase 3 CARTITUDE-4 trial enrolled patients at least 18 years of age with lenalidomide-refractory multiple myeloma who had received 1 to 3 prior lines of therapy that included a PI and IMiD.¹ Prior treatment with CAR T-cell therapy or BCMA-targeting therapy was not permitted. An ECOG performance status of 0 or 1 was required for enrollment.

Patients were randomly assigned to receive cilta-cel or standard-of-care therapy with pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd), or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd).

Previous analyses of CARTITUDE-4 showed that survival and safety outcomes varied by cytogenetic risk and response to bridging therapy, and that patients with high- or standard-risk cytogenetics treated with cilta-cel had improved PFS and OS compared with standard of care. In the cilta-cel arm, patients received briding therapy with at least 1 cycle of PVd or DPd.

PFS served as the trial’s primary end point, with secondary end points comprising complete response or better rate, overall response rate, minimal residual disease negativity–rate, OS, and safety.

Previously reported long-term data from CARTITUDE-4 suggested a potential cure fraction for patients with standard-risk disease treated with cilta-cel.³

The cytogenetic subgroup analysis presented at EHA 2026 examined efficacy and safety outcomes in the 176 patients who received cilta-cel as study treatment at a median follow-up of 33.6 months, with patients stratified into 4 subgroups by cytogenetic risk and bridging therapy response.¹

What effect did bridging therapy response have on safety outcomes?

Cytokine release syndrome occurred across all subgroups, with rates of 73.4% in the high-risk PR or better subgroup, 82.9% in the high-risk, less than PR subgroup, 70.0% in the standard-risk, PR or better subgroup, and 84.2% in the standard-risk, less than PR subgroup.

Grade 3 or higher infections were observed in 43.8% of high-risk, PR or better patients and 48.8% of high-risk less than PR patients. These rates were 30.0% and 26.3% in the standard-risk PR or better and less than PR groups, respectively.

Notably, no cases of IEC-parkinsonism were observed in patients who achieved PR or better to bridging therapy in either cytogenetic subgroup; 1 case (2.4%) occurred in the high-risk, less than PR group.

Non-relapse mortality (NRM) rates were 10.9%, 14.6%, 5.0%, and 21.1% in the high-risk, PR or better; high-risk, less than PR; standard-risk, PR or better; and standard-risk, less than PR groups, respectively, with infections representing a key contributor to NRM in patients with less than PR to bridging therapy.

References

1. van de Donk NWCJ, Mina R, Touzeau C, et al. Ciltacabtagene autoleucel in lenalidomide-refractory multiple myeloma responding to bridging therapy: CARTITUDE-4 cytogenetic subgroup analysis. Presented at: 2026 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PF767.
2. Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed June 12, 2026. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
3. Costa L, Oriol A, Dytfield D, et al. Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed/refractory multiple myeloma. Blood. 2025;146(suppl 1):94. doi:10.1182/blood-2025-94