CASSIOPEIA: What the Multiple Myeloma Trial Found

What myeloma is, in one paragraph

Plasma cells are white blood cells that make antibodies. NCI explains that they grow from B lymphocytes in the bone marrow. They normally appear when the body meets a virus or a bacterium.

In multiple myeloma, abnormal plasma cells build up in the marrow. They crowd out healthy blood cells. They weaken bone. And they pour out a useless antibody protein, called M protein, that can thicken the blood.

Our overview of multiple myeloma covers the disease itself.

The question CASSIOPEIA asked

In Europe, one regimen was standard for someone newly diagnosed and fit enough for a stem cell transplant. It was a three-drug combination called VTd: bortezomib, thalidomide and dexamethasone. It was given before and after the transplant.

The trial asked a narrow question. Does adding a fourth drug, daratumumab, make the response deeper?

Daratumumab is an antibody aimed at CD38. That is a protein on the surface of plasma cells, myeloma cells included.

How it was set up

ClinicalTrials.gov records NCT02541383 as a phase 3 trial that opened in September 2015, with 1,085 participants and primary completion on 27 August 2020.

The published first part enrolled those 1,085 people at 111 European sites. Enrollment ran from September 2015 to August 2017. The split was even. Five hundred and forty-three got daratumumab plus VTd. Five hundred and forty-two got VTd alone. Everyone had four cycles before the transplant and two after it.

The main measure was stringent complete response, assessed 100 days after transplantation.

What "stringent complete response" means

This is where the trial needs unpacking. The endpoint is not survival.

A complete response means the usual tests can no longer find signs of myeloma. Stringent complete response is a tighter version of that, set by extra laboratory criteria.

So it measures how deep the treatment went. It does not measure how long anyone lived. Our page on clinical trial phases covers why a trial's chosen endpoint decides what it can tell you.

The results

At day 100 after transplant, 157 of 543 people on daratumumab plus VTd had reached stringent complete response. That is 29%. In the VTd group it was 110 of 542, or 20%. The odds ratio was 1.60.

Deeper responses ran the same way. Complete response or better was reached by 39% against 26%. Then there is minimal residual disease. A test that can find one myeloma cell in 100,000 found none in 64% of the daratumumab group and 44% of the other.

Median progression-free survival was not reached in either group. That means fewer than half of each group had relapsed when the analysis was done. The hazard ratio favored daratumumab at 0.47.

Forty-six deaths occurred during the study: 14 in the daratumumab group and 32 in the VTd group.

The most common severe side effects were low neutrophils, at 28% against 15%; low lymphocytes, at 17% against 10%; and mouth sores, at 13% against 16%.

What changed afterward

The current prescribing information for the under-the-skin form of daratumumab names this exact use. It lists myeloma with bortezomib, thalidomide and dexamethasone, for newly diagnosed patients eligible for a stem cell transplant. That is the CASSIOPEIA regimen, on the label.

For context, the American Cancer Society projects about 36,000 new myeloma diagnoses in the United States in 2026 and about 10,850 deaths; SEER, the federal cancer surveillance program, republishes those projections alongside its own measurements. SEER's own figures put the median age at diagnosis at 69 and five-year relative survival at 63.7% for people diagnosed from 2016 through 2022. In 1975 the same figure was about 26%.

Those are registry averages describing a population, not a forecast for any person.

What this does not mean

• The main endpoint was response depth at day 100, not survival. Deeper responses tend to go with better outcomes in myeloma. But this trial was not built to prove that for this regimen.
• Median progression-free survival was not reached, so the durability question was still open. A second part of the trial, on maintenance, was still running when this report appeared.
• Everyone here was newly diagnosed and fit enough for a transplant. That leaves out a large share of people with myeloma. The median age at diagnosis is 69.
• Adding a fourth drug added toxicity. Severe neutropenia nearly doubled.
• Nothing here is a treatment recommendation. Our page on questions to ask about a clinical trial is a starting point for that conversation.

Sources

• NCBI eutils: Moreau et al., Lancet 2019;394:29-38 (CASSIOPEIA, PMID 31171419)
• ClinicalTrials.gov API v2: NCT02541383 (CASSIOPEIA)
• openFDA drug label API: DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)
• NCI PDQ: Plasma Cell Neoplasms Including Multiple Myeloma Treatment (Patient Version)
• NCI SEER Stat Facts: Myeloma

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.

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