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Upfront Darzalex Combo May Be More Beneficial in the First-Line Setting for Transplant-Ineligible Myeloma Than Alternatives


An expert from the Mayo Clinic explained that the use of a combination of drugs including Darzalex in the first-line setting may lead to better outcomes for patients with multiple myeloma instead of other first-line standard-of-care options.

It may be best for patients with transplant-ineligible multiple myeloma to receive first-line therapy with Darzalex (daratumumab), Revlimid (lenalidomide) and dexamethasone — a combination referred to as D-Rd — as opposed to an alternative standard of care therapy in the first-line and D-Rd in the second-line setting, according to an expert.

In discussing recent findings from three clinical trials presented at the 2021 American Society of Hematology (ASH) Annual Meeting, Dr. Rafael Fonesca explained that patients should discuss their treatment options with their health care providers to find the best route for addressing their cancer.

The trials’ data demonstrated that D-Rd given to patients with transplant-ineligible multiple myeloma as a first-line treatment yielded better overall survival benefits, compared with waiting to give it as a second-line treatment after giving a Velcade-based triplet therapy — Velcade (bortezomib), Revlimid and dexamethasone (VRd). The analysis Fonesca presented considered which standard of care option would have the best safety profile and efficacy in patients.

Fonesca, who is the director for Innovation and Transformational Relationships at the Mayo Clinic in Phoenix, Arizona, also noted that it’s important to consider different paths for patients who experience severe side effects, as some drugs can increase the chances of toxicities more so than others.

“In extreme cases, (neuropathy) can be quite painful and debilitating. And it's a toxicity we don't like to see. So just based on that alone, I have a preference for the use of the daratumumab regimen,” he said.


Make sure that you talk to your hematologist about the various treatment options that are available. I think anyone in the community would say both of them (Darzalex- and Velcade-based regimens) are standard. But if I, say, walk patients through the decision process, and I meet with them, I would normally go and say that while I recognize that, strictly speaking from a scientific perspective, this is best addressed through those trials that looking forward, we call them prospective randomized trials, you get the purest of the answers. Given that both of these regimens are supported by experts from across the United States and institutional guidelines like ours and guidelines like the (National Comprehensive Cancer Network), I think it's fair to ask those questions (like) “What should I use?”

And in particular, I like to use the regimens that do not contain bortezomib because of the risk of neuropathy. Neuropathy, if you're not familiar with this, is the inflammation and decreased function that people can get in the nerves that go to your feet and your hands, which sometimes could be very mild, something like just feeling numbness. But in extreme cases can be quite painful and debilitating. And it's a toxicity we don't like to see. So just based on that alone, I have a preference for the use of the daratumumab regimen.

Now, in the studies we presented, which again, is a simulation based on big data analysis, we would suggest that also there's better efficacy for doing that, but this is something you should discuss with your treating physician.

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