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CARTITUDE-1: What the Multiple Myeloma Trial Found
CARTITUDE-1 tested ciltacabtagene CAR T-cell therapy in multiple myeloma, measuring objective response. Plain-language summary of a positive result on its main measure — and what it doesn't mean.
Original commentary from the Cancer Explained editorial team.
Please note: this page is educational only — it is not medical advice, and it does not speculate about anyone’s health beyond reliable public reporting. For questions about your own health, talk with your healthcare team.
Two grips instead of one
Ciltacabtagene autoleucel, shortened to cilta-cel and sold as Carvykti, is a CAR T-cell therapy for myeloma. Like others in its class it aims at B-cell maturation antigen, or BCMA, a protein on myeloma cells.
Its design differs in one respect. The receptor carries two single-domain antibodies that bind BCMA, rather than one. The idea is a firmer grip on the target cell.
The rest follows the usual CAR T route. A patient's T cells are collected, engineered in a laboratory to carry the receptor, grown, and given back by infusion. Our page on CAR T-cell therapy sets out that process.
Who was studied
CARTITUDE-1 ran at 16 centers in the United States. It was single-arm and open-label, meaning everyone received the treatment and everyone knew it.
It combined two phases. Phase 1b established safety and the recommended dose. Phase 2 measured overall response rate.
Entry required adults with myeloma and good functional status. They had to have had three or more previous lines of treatment. Or they had to be resistant to both a proteasome inhibitor and an immunomodulatory drug. All had already had a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody.
Between July 2018 and October 2019, 113 patients were enrolled. Ninety-seven received the infusion at the recommended dose. Their median number of previous therapies was six.
The response numbers
At a median follow-up of 12.4 months:
- 94 of 97 patients responded. That is 97%, with a confidence interval from 91.2% to 99.4%.
- 65 patients, or 67%, reached stringent complete response, the strictest definition of no detectable myeloma by standard tests.
- Median time to first response was 1 month.
- Responses deepened over time rather than fading.
A 97% response rate in people who had already exhausted six lines of treatment is an unusual result. It is the reason this trial is still discussed.
The numbers that were not reached
Three key figures in this trial were "not reached", and that phrase is easy to misread.
Median duration of response was not reached. Median progression-free survival was not reached. That does not mean forever. It means that when the data were locked, fewer than half the patients had relapsed, so no midpoint could be calculated yet.
What could be calculated were rates at a fixed time. The 12-month progression-free rate was 77%, and the 12-month overall survival rate was 89%.
Read those as a snapshot at one year in a group with advanced disease. They are not a long-term result. Our page on trial endpoints explains why "not reached" is a statement about follow-up length.
What it cost
The safety data are as striking as the response data, in the other direction.
Severe blood count problems were near-universal. Grade 3 to 4 neutropenia occurred in 95% of patients, anemia in 68%, low white cells in 61%, low platelets in 60% and low lymphocytes in 50%.
Cytokine release syndrome occurred in 95% of patients, though only 4% at grade 3 or 4. Median time to onset was 7 days. Median duration was 4 days. It resolved in every patient but one, who had grade 5 cytokine release syndrome with hemophagocytic lymphohistiocytosis.
CAR T-cell neurotoxicity occurred in 21% of patients, with 9% at grade 3 or 4.
Fourteen people in the study died: six from treatment-related adverse events, five from the myeloma progressing, and three from causes unrelated to treatment.
Those six treatment-related deaths sit alongside the 97% response rate. Both belong in any honest summary.
The label since
Carvykti was first approved in the United States in 2022. Its current indication covers adults with relapsed or refractory myeloma who have had at least one prior line of therapy. That line must have included a proteasome inhibitor and an immunomodulatory agent. The disease must also be refractory to lenalidomide.
That is far earlier in the course than CARTITUDE-1's population, which had a median of six prior therapies.
The boxed warning has grown with experience. It now covers cytokine release syndrome and neurotoxicity. It also covers parkinsonism and Guillain-Barre syndrome. It covers hemophagocytic lymphohistiocytosis, and low blood counts that last or return. It covers inflammation of the bowel. And it covers second blood cancers, including myelodysplastic syndrome, acute myeloid leukemia and T-cell cancers.
Before infusion, patients receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Preventive steroids are avoided, and tocilizumab must be confirmed available first.
When to get checked
CAR T is for people already living with myeloma. The disease itself has no screening test and is usually found through symptoms or an odd blood result. Ask a doctor about:
- Bone pain that does not shift, particularly in the back, ribs or hips.
- A fracture after a minor injury.
- Infections that keep returning or clear slowly.
- Tiredness and breathlessness suggesting anemia.
- A blood test showing raised calcium, low hemoglobin or worsening kidney function.
Our page on multiple myeloma covers what the work-up involves.
What this trial cannot tell you
There was no comparison group, so nothing here says cilta-cel is better than any alternative. It says what happened to 97 people who received it.
The follow-up was short. A median of 12.4 months cannot describe how long remissions last, which is exactly why the key medians were not reached.
The population was selected. Everyone had good performance status and was well enough for an intensive treatment, and 16 patients enrolled never received the infusion.
And the toxicity is not a footnote to the efficacy. Almost everyone had severe blood count suppression, almost everyone had cytokine release syndrome, and six people died from the treatment. A 97% response rate does not describe the whole experience.
Sources
- Lancet 2021, Ciltacabtagene autoleucel in patients with relapsed or refractory multiple myeloma (CARTITUDE-1), PMID 34175021 — https://pubmed.ncbi.nlm.nih.gov/34175021/
- ClinicalTrials.gov v2 API, NCT03548207 (CARTITUDE-1) — https://clinicaltrials.gov/api/v2/studies/NCT03548207
- DailyMed, CARVYKTI (ciltacabtagene autoleucel) prescribing information — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7d040b91-3fb8-41db-ba7f-60a36f06e2c2
- NCI PDQ, Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (Health Professional Version) — https://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq
How this article was prepared
An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.
The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.
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