DETERMINATION: What the Multiple Myeloma Trial Found

A trial about whether to do something, not what drug to give

Most cancer trials compare drugs. This one compared a decision.

Stem cell transplantation has been part of myeloma treatment for decades. The person's own blood-forming stem cells are collected, a very high dose of the chemotherapy drug melphalan is given to wipe out the marrow, and the stored cells are returned to rebuild it. It is demanding, and it takes weeks.

Newer drug combinations got good enough that a real question arose: with modern drugs, is the transplant still worth doing up front?

How the question was posed

ClinicalTrials.gov records NCT01208662 as a phase 3 trial that opened in September 2010, with 729 participants.

Everyone was between 18 and 65 and had symptomatic, newly diagnosed myeloma. All received one cycle of RVD, a three-drug combination of lenalidomide, bortezomib and dexamethasone.

Then came the split. Both groups had two more RVD cycles plus stem cell collection. After that, one group had five further RVD cycles and no transplant. The other had high-dose melphalan with a transplant, then two more RVD cycles.

Both groups then took lenalidomide until the disease progressed or the side effects became unacceptable.

The main measure was progression-free survival. The trial was funded by the National Heart, Lung, and Blood Institute and others, which matters: this was an academic question rather than a company one.

Note what the design does not test. Nobody was denied a transplant forever. The comparison is transplant now against transplant kept in reserve. Our page on clinical trials compared with standard treatment covers why that framing changes how a result should be read.

The results

Three hundred and fifty-seven people were in the RVD-alone group and 365 in the transplant group. Median follow-up was 76 months, so more than six years.

Median progression-free survival was 46.2 months without the transplant and 67.5 months with it. The risk of progression or death was 53% higher in the group that skipped the transplant, with a hazard ratio of 1.53.

That is a difference of about 21 months in the median. It is a large result on the trial's main measure.

Then the second finding, which is the one that made this trial argued over.

Five-year survival was 79.2% without the transplant and 80.7% with it. The hazard ratio for death was 1.10, and its confidence interval ran from 0.73 to 1.65, which includes 1. In plain terms, no overall survival advantage was seen.

Response rates were also close. A partial response or better was reached by 95.0% and 97.5%. A complete response or better by 42.0% and 46.8%. Neither difference was statistically significant.

What it cost

Severe treatment-related side effects, graded 3 or higher, occurred in 78.2% of the RVD-alone group and 94.2% of the transplant group.

Both numbers are high. The gap between them is what the transplant adds, and it is the other half of the trade the trial put on the table.

Reading a result that points two ways

This is a case where the honest summary is genuinely split, and any page that reports only one half is misleading.

Transplant delayed progression by nearly two years in the median. Transplant did not extend life over the follow-up available. Transplant caused more severe side effects.

None of those three sentences cancels the others. Which one matters most depends on what a person is weighing, and that is a conversation with a care team rather than a conclusion a trial can hand down.

Our page on clinical trial phases explains why progression-free survival and overall survival can diverge, and our overview of multiple myeloma covers the disease.

The disease, briefly

NCI describes myeloma as a disease in which abnormal plasma cells build up in the bone marrow. They crowd out normal blood cell production, damage bone, and produce an antibody protein, called M protein, that serves no purpose.

For 2026 the American Cancer Society projects about 36,000 new myeloma diagnoses in the United States and about 10,850 deaths, and SEER, the federal cancer surveillance program, reprints them. Median age at diagnosis, from SEER's own records, is 69.

Five-year relative survival is 63.7% for people diagnosed from 2016 through 2022. In 1975 the same figure was about 26%.

Those are registry averages across a whole population, not a statement about any individual.

What this story cannot tell you

• The trial enrolled people aged 18 to 65. The median age at myeloma diagnosis is 69, so most people with this disease were outside the eligible range.
• Progression-free survival and overall survival answered differently here. A trial can be positive on its primary endpoint and neutral on survival, and both facts are real.
• Follow-up was six years. Longer follow-up could shift the survival picture in either direction.
• Treatment has continued to move since enrollment. Four-drug combinations and newer maintenance approaches came later, and this comparison does not include them.
• Nothing here recommends a course of action. Our page on questions to ask about a clinical trial covers how to open that discussion.

Sources

• NCBI eutils: Richardson et al., N Engl J Med 2022;387:132-147 (DETERMINATION, PMID 35660812)
• ClinicalTrials.gov API v2: NCT01208662 (DETERMINATION)
• 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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