Drug Combos Improve Outcomes in Newly Diagnosed Myeloma

The treatment plan for patients with newly diagnosed multiple myeloma often relies heavily on whether the patient is healthy enough to undergo a stem cell transplant. And, in both the transplant-eligible and -ineligible populations, there are new drug combinations that are continually being explored, explained Dr. Malin Hultcrantz.

“When someone comes into clinic and has a new diagnosis of multiple myeloma, we look at many different things, but we mainly divide patients into two different groups. One is called transplant eligible, meaning that they are in that group that would be able to go through a transplant. The other one is transplant … ineligible, and mostly those are on the older side where transplant can be a little bit tough,” Hultcrantz said.

At CURE®’s recent Educated Patient® Multiple Myeloma Summit, Hultcrantz, associate attending physician and assistant professor, myeloma service, at Memorial Sloan Kettering Cancer Center in New York, discussed treatment options for patients who are newly diagnosed with multiple myeloma.

Transplant-Eligible Myeloma

When a patient is deemed fit enough by their health care team to undergo a stem cell transplant, they can expect to first be treated with a combination of drugs to reduce the number of myeloma cells in the bone marrow. This treatment, called “induction therapy,” is commonly administered as one of the following drug combinations:

• Darzalex (daratumumab) plus Revlimid (lenalidomide), Velcade (bortezomib) and dexamethasone — a combination referred to as D-VRd
• Darzalex, Kyprolis (carfilzomib), Revlimid and dexamethasone (D-KRd)
• Sarclisa (isatuximab-irfc), Velcade, Revlimid and dexamethasone (Isa-VRd)
• Sarclisa, Kyprolis, Revlimid and dexamethasone (Isa-KRd)

After induction therapy, Hultcrantz mentioned that everyone who is eligible for a transplant should undergo the procedure.

“The question, then, is should we do it upfront or should we delay?” she said. “There’s no right or wrong answer. We look at different [patient characteristics].”

Hultcrantz mentioned that that clinicians consider risk profile, response rate (how effectively the induction therapy killed off myeloma cells), age and performance status (how well a patient can complete daily tasks independently) when determining the next best steps regarding a stem cell transplant.

“For someone who is [in their] late 60s or early 70s, it’s probably better to do their transplant sooner rather than later,” Hultcrantz said.

Transplant-Ineligible Myeloma

Multi-drug regimens are also utilized in patients with newly diagnosed myeloma who are not eligible for transplant.

“We’ve had, for a long time, three-drug regimens or even two-drug regimens,” Hultcrantz said. “What we’ve seen presented at the ASCO [Annual Meeting], we’re starting to see four-drug regimens also in that transplant-ineligible group.”

READ MORE: 4-Drug Regimen Boosts Time to Progression in Newly Diagnosed Myeloma

For example, at a median follow-up of five years, the IMROZ trial showed that Isa-VRD followed by Isa-Rd reduced the risk of disease progression or death by 40.4% compared to VRd.

Patients with newly diagnosed transplant-ineligible myeloma may expect to have induction therapy with a three- or four-drug regimen, such as D-RD, Isa-VRd or Isa-RD, followed by maintenance therapy (therapy given to prevent cancer from coming back) consisting of drug duo, such as Darzalex and Revlimid or Sarclisa and Revlimid.

For patients who are frail, two-drug regimens (Darzalex or Revlimid plus dexamethasone) may be used as upfront induction therapy.

CAR-T Cell Therapy and Future Directions

Researchers and clinicians are now also investigating the use of CAR-T cell therapy in lieu of transplant for those who are eligible and as another treatment option for those who are not eligible for transplant.

Hultcrantz mentioned two ongoing trials — CARTITUDE-6 is comparing outcomes of transplant versus the CAR-T cell therapy, Carvykti (ciltacabtagene autoleucel) followed by maintenance therapy in patients with newly diagnosed transplant-eligible myeloma. Meanwhile, CARTITUDE-5 is investigating the efficacy of induction VRd followed by Carvykti and maintenance thearpy in patients who are not eligible for transplant.

“One thing that we do know is that we have a lot of treatment options, and the future is very bright,” Hultcrantz said.

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