Hematologic oncologists discuss toxicities seen with ixazomib, lenalidomide, and dexamethasone (IRd) compared with lenalidomide and dexamethasone (Rd).
Suzanne Fanning, DO: When we look at toxicities throughout this trial, thankfully we see some good similarities between the triplet compared with the doublet. The vast majority of the toxicities are going be hematologic in nature, so we can see the anemia, neutropenia, and thrombocytopenia listed on the left side of the slide. We see more grade 3 neutropenia in the IRd [ixazomib, lenalidomide, dexamethasone] arm. There were more infections reported in the IRd [ixazomib, lenalidomide, dexamethasone] arm. When we look at issues of fatigue, we see good similarities. I mentioned the infectious risk that was noted. When we look at other factors, we see more neuropathy in the IRd [ixazomib, lenalidomide, dexamethasone] combination. Remember that this trial, compared with the TOURMALINE trial, didn’t have a more allowable amount of neuropathy to go on to these therapies. This was not a clinical trial, so the practitioners were treating patients with the ixazomib–Rd [lenalidomide, dexamethasone] combination. We did see more grade 3 neuropathy. However, the investigators did think this was more likely associated with pretreatment. There were similar amounts of nausea and anorexia and a little more diarrhea in the IRd [ixazomib, lenalidomide, dexamethasone] combination. We can see constipation, rash listed. Overall, it’s pretty similarly well tolerated with regard to toxicities.
Joshua Richter, MD: Absolutely. I couldn’t agree more on all accounts. The 1 small thing is that in a lot of the trials in myeloma, we look at 3- vs 2-drug combos...and the triplet wins out—it always does—patients have a longer progression-free survival…. Besides getting more Revlimid [lenalidomide] and more Ninlaro [ixazomib], there’s also more dexamethasone that they got over time because we’re following them on steroids for a longer period. Infection rates are higher here, especially the grade 1/2. Some of this may be Ninlaro related, but a good amount may be dexamethasone related. With trials like TOURMALINE, we also saw higher risks of cataracts, hypertension, hyperglycemia, and edema, and some of that is more exposure to steroids over a longer period of time.
Transcript edited for clarity.