Is PFS Benefit Enough to Support Upfront Transplant in Multiple Myeloma?

DETERMINATION is one of many recent randomized trials in newly diagnosed transplant-eligible multiple myeloma to show a clear progression-free survival (PFS) benefit with upfront autologous stem-cell transplantation (ASCT) versus non-transplantation consolidation, yet no advantage in overall survival.

A survey study reported at the recent American Society of Hematology meeting asked oncologists and hematologists to evaluate their perceptions of the trial, and to describe the benefits and barriers of integrating ASCT into first-line therapy for patients with newly diagnosed transplant-eligible multiple myeloma.

In this exclusive MedPage Today video, Bruce Feinberg, DO, of Cardinal Health Specialty Solutions in Dublin, Ohio, discusses the survey findings.

Following is a transcript of his remarks:

Multiple myeloma is undergoing kind of an explosion of new therapeutics, which are the end result of rapidly increasing knowledge of underlying mechanisms of disease. And historically in oncology, as new therapeutics come into the market, it’s typically an additive phenomenon. So you have drug A, and then drug B comes along, and it’s A plus B versus A. And then you have drug C and it becomes A plus B plus C versus A plus B.

And we seem to be in this kind of evolution right now within myeloma — it’s not unique to myeloma, but it’s happening much faster. And myeloma seemed like from a research perspective, a really interesting disease state to understand from a standpoint of physician choice architecture. The old saying is that where goes the pen, goes the purse. Physicians hold the pen they prescribe.

And so understanding this choice architecture around prescribing and at what point as the newer therapeutics become more and more effective, is it going to be this additive? So when we’ve moved from doublet induction therapy to triplet induction therapy, we’ve added in maintenance, we’ve added in a stem cell consolidation phase of treatment. And so patients undergo a tremendous amount of treatment.

They are living longer and longer. At some point, it begs the question, are we doing more than we need?

So we start with more is more, and at some point more may be less. And that’s the question that’s being asked in the DETERMINATION trial. Can you delay autologous stem cell transplant, given the quality and the effectiveness of the triplet therapies with induction, in providing a durable deep response for the disease?

Again, it’s not unique to oncology. The pioneer of this was a guy named Larry Einhorn, a testicular cancer researcher, and testicular was the classic first solid tumor in which we saw such impressive results that were durable, that we believed we could cure people with it. And he started to ask that question, can we do less? We’re curing people, but the cure is coming at a huge cost. Can we do less? And Larry was a brilliant trialist and, and especially in methodologic design, where he only adjusted one variable at a time and did these great sequential studies.

We’re at that place now in a lot of diseases. We’re asking that question in chronic lymphocytic leukemia — can we do fixed-dosed induction and not have patients on continuous treatment for life? And we’re asking that question also in myeloma, in the case of DETERMINATION, specifically around the consolidation transplant, immediate or delayed. Because in the end it’s always been efficacy and toxicity. That shouldn’t be lost.

The question is, are they the only two viable assessments? How important is the patient centricity aspect of financial toxicity, burden of treatment, and these other factors? And then on a societal level, in reference to payers — they’re not only taking care, they’re not only responsible for managing the cost of cancer patients. They’re the diabetics, and the patients with heart failure. And we can go down the list and they’ve got to start to figure out how do they apportion the limited dollars they have across all those different what are now chronic disease states, even though they may be life-threatening, as we make them more chronic and patients are living again up to decades with these diseases, there it is a finite number of dollars.

And so trying to ask those hard questions, do the research in a way which can be validated, sample sizes that are large enough, ask in a way that the questions are not open-ended but specific and allow us to address outcomes that are meaningful to the different stakeholders. We feel that’s a role that we can play as kind of a middleman, so to speak, across all the stakeholders in the industry.

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