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KarMMa: What the Multiple Myeloma Trial Found
KarMMa tested idecabtagene 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.
Rebuilding a patient's own T cells
Idecabtagene vicleucel, shortened to ide-cel and sold as Abecma, is a CAR T-cell therapy. The idea is to turn a person's own immune cells into a drug.
T cells are collected from the patient's blood. In a lab they are changed to carry a chimeric antigen receptor. That is a built protein on the cell surface that spots one target. Here the target is B-cell maturation antigen, or BCMA. It sits on myeloma cells. The modified cells are grown in number and returned by infusion.
Because the cells come from the patient and are given back to the same person, the treatment is called autologous. Our page on CAR T-cell therapy walks through the manufacturing steps and the wait involved.
Who was in the trial
KarMMa, registered as NCT03361748, was a phase 2 study with a single group and no comparison arm. Its primary outcome measure was overall response rate.
Entry required myeloma that had come back or stopped responding after at least three previous regimens. Those regimens had to include a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. In other words, everyone had already used the main classes of myeloma treatment.
Of 140 patients enrolled, 128 actually received the infusion. Twelve did not. That is a real feature of the treatment, not a rounding error. Making the cells takes weeks. Some people become too unwell in that time.
What it found
At a median follow-up of 13.3 months:
- 94 of 128 treated patients, or 73%, had a response.
- 42 of 128, or 33%, had a complete response or better.
- Minimal residual disease was undetectable in 33 patients. That is 26% of everyone treated, and 79% of those with a complete response.
- Median progression-free survival was 8.8 months, with a 95% confidence interval from 5.6 to 11.6 months.
Minimal residual disease testing looks for myeloma cells at a threshold of fewer than one in 100,000 nucleated cells. It is a far more sensitive measure than standard blood tests.
The conclusion the authors drew was measured: ide-cel produced responses in most of these heavily pretreated patients, and almost all of them had grade 3 or 4 side effects.
Why the design limits what can be claimed
Everyone in KarMMa received the treatment. There was no control group, so there is nothing to compare the results against except history.
That matters most for the survival figure. An 8.8-month median progression-free survival cannot be read as "better than X" because no X was measured. Our page on clinical trial phases explains why single-arm phase 2 studies answer a narrower question than randomized trials.
What a single-arm study can show is whether a response happens at all, and how often. Here it was a group with no standard options left. Responses to further usual treatment are uncommon in that group. A 73% response rate was enough to change practice.
The toxicity is part of the deal
The Abecma label carries a boxed warning covering five distinct dangers, and the trial data show why.
Cytokine release syndrome occurred in 107 of 128 patients, 84%, with 5% at grade 3 or higher. It is a body-wide reaction as the new cells switch on. It brings fever, low blood pressure and trouble breathing. It can be fatal. It is treated with tocilizumab, an antibody that blocks one of the signals, with or without steroids.
Neurologic toxicity occurred in 23 patients, 18%, and reached grade 3 in 4 patients. It can appear alongside cytokine release syndrome, after it resolves, or without it at all.
Blood count suppression was near-universal: neutropenia in 91%, anemia in 70%, low platelets in 63%. The label warns that prolonged low counts can lead to bleeding and infection, including fatal outcomes.
The boxed warning names two more. One is hemophagocytic lymphohistiocytosis, a severe over-reaction of the immune system. The other is T-cell cancers seen after BCMA- and CD19-directed CAR T therapies.
What the treatment involves in practice
The label sets out a sequence that is unlike taking a drug.
Cells are collected, sent for manufacture, and returned weeks later. Before infusion the patient receives lymphodepleting chemotherapy with cyclophosphamide and fludarabine, which clears space for the engineered cells to expand.
Premedication with acetaminophen and an antihistamine follows. Steroids are avoided beforehand, because they would blunt the very immune response the treatment depends on. Tocilizumab must be confirmed as available before the infusion is given.
The label tells patients to stay within reach of a healthcare facility for at least a week after the infusion, and to avoid driving for at least that long.
The current label covers adults with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. That is one line earlier than the KarMMa population.
When to get checked
CAR T is for people already diagnosed. Myeloma itself is usually found through symptoms or a routine blood result. NCI's markers of active disease include a calcium above the normal range. Others are a creatinine over 2 mg/dL, or creatinine clearance under 40 mL/min. Others again are hemoglobin under 10.0 g/dL, and holes in bone on a scan.
Ask a doctor about bone pain that does not shift, especially in the back or ribs, or a bone that breaks after a minor knock. Also about repeated infections, unexplained tiredness, or a blood test showing high calcium or worsening kidney function. Our page on multiple myeloma covers the work-up.
What this trial cannot tell you
It cannot tell you whether ide-cel prolongs life. Progression-free survival was measured; overall survival against an alternative was not, because there was no alternative arm.
It cannot tell you the results hold outside the trial population. Everyone enrolled was well enough to be considered for an intensive treatment, which is a selected group.
It cannot promise the treatment will be available in time. Twelve of 140 enrolled patients never received their cells.
And a response is not a permanent one. The median progression-free survival was under a year, which means most people in KarMMa did eventually progress. That is a meaningful result in this setting, and it is not a finish line.
Sources
- NEJM, Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma, PMID 33626253, record retrieved from the NCBI eutils API — https://pubmed.ncbi.nlm.nih.gov/33626253/
- ClinicalTrials.gov v2 API, NCT03361748 (KarMMa) — https://clinicaltrials.gov/api/v2/studies/NCT03361748
- DailyMed, ABECMA (idecabtagene vicleucel) prescribing information — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b90c1fe7-f5cc-464e-958a-af36e9c26d7c
- 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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Prevention, possible warning signs, screening, and diagnosis
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