Which is Better: Three Drugs or Four Drugs?
- The drug combination used to treat newly diagnosed multiple myeloma is up for debate, with some believing four drugs are better than three.
- The three-drug combination includes a proteasome inhibitor, an immunotherapy drug and a steroid. Those drugs are either Velcade, lenalidomide and dexamethasone (VRD), or Kyprolis, lenalidomide and dexamethasone (KRD).
- The four-drug combination involves adding monoclonal antibody drug daratumumab to either the VRD or KRD drug regimens.
That combination of drugs is up for debate among multiple myeloma specialists, with an increasing number of doctors believing that using a four-drug combination is more effective than the traditional three-drug combination.
Three-Drug Combinations
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Many doctors, Dr. Kazandjian says, "including us here in Miami, tend to really believe that KRD is a little more superior than VRD in the initial phases (of multiple myeloma treatment)."
There is another three-drug combination commonly referred to as DRD, which is a combination of daratumumab (brand name: Darzalex), lenalidomide and dexamethasone. This combination is different because instead of using a proteasome inhibitor drug, the regime uses a monoclonal antibody drug, daratumumab.
Which drug combination your doctor suggests depends on whether or not you are eligible to receive a stem cell transplant. However, Dr. Kazandjian says that is not always the best indicator of which drug combination you receive.
"Traditionally, we've lumped patients into transplant-eligible or transplant-ineligible. I think that's probably also not such a great term nowadays. Plenty of patients who are transplant eligible, meaning they're fit enough to receive a transplant may not need a transplant, or may not opt for a transplant," he says.
Dr. Kazandjian explains that the aforementioned drug combinations are the "main" treatment options for newly diagnosed multiple myeloma patients right now.
But, "as I alluded to, very quickly, we're moving on to even four-drug combinations to try to get deeper and deeper remissions," he adds.
Four-Drug Combination
The four-drug combination Dr. Kazandjian is referring to includes the previously mentioned three-drug combinations known as VRD or KRD, but adding monoclonal antibody drug daratumumab to the mix. Dr. Kazandjian says this is a drug combination he is moving toward with his newly diagnosed multiple myeloma patients.
Dr. Kazandjian cites a study where transplant-eligible patients received the VRD drug combination, both with and without daratumumab. The study reported significant activity with the four-drug combination.
"If you can add daratumumab to VRD, how about adding it to the newer triple KRD?" Dr. Kazandjian says, citing another study, this time from his University of Miami colleague, Dr. C. Ola Landgren, where daratumumab was added to the three-drug combination known as KRD.
The results of these studies are "fairly convincing that four drugs may be the way to go," Dr. Kazandjian says.
Darzalex vs. Sarclisa for Multiple Myeloma
While there is debate about whether to add a fourth drug to the induction therapy regimen, there is also debate about which monoclonal antibody drug is best to use in combination with the "gold standard" three-drug combos.
Those two drugs in question are daratumumab (brand name: Darzalex) and isatuximab (brand name: Sarclisa).
Dr. Kazandjian says that regardless of the debate, there is not much difference between the two; something he says his colleagues would likely agree with.
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"I don't think there's a major difference between the two drugs," he says. "I think it would be hard to say one is better than the other, and we'll never have a clinical trial that compares the other one."
The only difference Dr. Kazandjian cites is the frequency in which the drugs are given to multiple myeloma patients. Isatuximab is given every week or every other week, whereas daratumumab, at some point, becomes a drug that is given once a month.
"But (for) me, and I'm sure many of my colleagues many times have tried to increase the frequency of daratumumab to make it a little more active if a patient is slowly relapsing or something," Dr. Kazandjian says. "So, the bottom line is I think they are both good drugs. Isatuximab now has similar studies that daratumumab has in the newly diagnosed setting."
"It is definitely a very valid alternative to daratumumab."
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