Ixa-Pom-Dex as Second-Line Therapy in Relapsed/Refractory MM: Alliance A061202
Rahul Banerjee, MD, FACP, discusses the Alliance A061202 trial, presenting the potential benefits and red flags of using ixazomib-pomalidomide-dexamethasone combination in relapsed myeloma treatment.
Transcript:
Judy Schreiber, PhD, RN: We’re going to move on to the next presentation from Dr Banerjee on the Alliance A061202 trial [NCT02004275]…then we’ll go back to questions and answers. Thank you.
Rahul Banerjee, MD, FACP: Wonderful. Very nice to meet you all, virtually or in person. I thought it was going to be a competition about puns, so I [titled] mine “Ixa-Pom-Dex as Second-Line Therapy: Swipe Left or Swipe Right.” Here are my disclosures. As you’ve heard from Dr Cowan, Dr Janakiram, and Dr Liu, there are a plethora of options. We have this luxury of riches and…early line treatment of relapsed myeloma. Comparing between trials is tricky, and…there [are] 2 caveats here. One, I’m comparing between trials…some of which only allowed 1 prior line, [whereas] some [are] allowed up to 3 prior lines. But you can see many options here, including daratumumab, isatuximab, CD38s, elotuzumab, belantamab, a [B-cell maturation antigen] target, ixazomib Pd—which is what I’ll be talking about—[and] selinexor. Then in terms of proteasome inhibitors [PIs], there’s also bortezomib, carfilzomib [Kyprolis], [and] lots of options.
Looking at this slide with all the caveats in place, you can see a couple of them where the active arm had a…median PFS [progression-free survival] of over 20 months, and that’s this ixa Pd study that I’ll talk about. You also see [the daratumumab/carfilzomib/dexamethasone] that was alluded to—the CANDOR trial [NCT03158688]—where [the PFS] was 28.4 months. Then with isatuximab, carfilzomib, [and] dexamethasone, [the PFS] was 35.7 months. How do you choose between all of these? First, I was not aware of this particular study of ixa-pom-dex [ixazomib, pomalidomide, dexamethasone], so I will be presenting an abstract and not an actual manuscript. This was presented last year at EHA and at IMS in Los Angeles, [California]. Dr Voorhees was the lead author [and] Dr Richardson [was] the senior author here, looking at ixa-pom-dex in patients who are progressing or having PD on lenalidomide.
So…relevant to the question I asked Dr Liu earlier, what if someone was having PD on lenalidomide? Dr Janakiram and Dr Cowan offered their takes, as well. So, this is an option. For patients who [were] having active progressive disease on first-line lenalidomide, [they] were allowed to be PI exposed but not PI refractory. You can see it was a cooperative group study here. [Of] the 2 arms, one was just Pd with pom 4 mg and the dexamethasone 20 to 40 mg weekly. The second arm got Pd plus ixazomib added as well. This is a poster or an abstract, so I don’t have all the data I would like. The median age was similar between the groups. I know nothing—very literally nothing—about the other demographics between the Pd and ixazomib Pd arms.
Conveniently, the abstract did not comment on some of the things I was very interested in with the addition of ixazomib, mainly infections and GI [gastrointestinal] toxicity. However, they did comment on hematologic toxicities, similar to what Dr Liu described earlier. You can see that…they didn’t report P values, but I would suggest that these grade 3 hematologic toxicities were higher with the addition of ixazomib plus pomalidomide plus dexamethasone vs just [pomalidomide and dexamethasone]. You can see lymphopenia, for example, grade 3 [or more] was 40%, [and] neutropenia [was] 37%. However, there were similar rates of discontinuation between arms for [adverse events].
The overall response rate was numerically higher with the addition of ixazomib. The median PFS was impressive—20.3 months with ixazomib Pd. So just as an example…in the first slide With the APOLLO trial [NCT03180736] of daratumumab [with pomalidomide and dexamethasone, the PFS] was…12.4 months, if I recall correctly. Then with ICARIA-MM [NCT02990338], [the PFS with] isa-pom-dex was…11 [to] 12 months or so. It’s pretty good. The [HR] was 0.377 for PFS events, and the [CI] was not reported. I Googled the best I possibly could to see [whether there [were] any updates since this abstract, and there [was] a press release from December 2021 that the DSMB [Data and Safety Monitoring Board] closed this study based on this overwhelming interim analysis that was favoring ixazomib.
So, should we swipe left or swipe right on ixa-pom-dex?... Swipe left means you pass on this, [whereas] swipe right says [you’re] interested. The point here is that with dating, everyone is right for someone, but everyone is not right for everybody. So, is this the combination you’re looking for in your patient? There are some positive signs. This is an all-oral regimen, as Dr Cowan, Dr Liu, [and] Dr Janakiram have alluded to. In abstract, they commented on this particularly during COVID-19, so this study started to have the analysis happen during the early years of COVID-19. And…oral is wonderful. [There is] clearly an improved median PFS.
There [are] a bunch of red flags here. Part of it is not the author’s fault—or maybe it is, there’s no manuscript for me to look at—but I don’t know the infectious risk or GI toxicities. This is…coming into my issue here. Again, grade 3 lymphopenia [and] grade 3 neutropenia are real. Those make me concerned about infections, particularly [in] my older, frailer patients. For those patients, I probably would want a CBC once a month, just in case someone’s at risk for those. If someone’s coming into a health care setting once a month for labs, why not use a parenteral drug? Why not use [isatuximab/carfilzomib/dexamethasone] or [daratumumab/carfilzomib/dexamethasone], for example, [spacing] out [the doses] to once a month if you end up dropping the [carfilzomib].
You could argue this with patients who live very remotely. I would argue that with the data with CARTITUDE-4 [NCT04181827], [which will] be presented later today, CAR T [chimeric antigen receptor T-cell therapy] is probably coming soon to [the second] line. I’d rather have them move to the big city…for a month or 2 [and] get CAR T-cell therapy and then go back as opposed to using one of these lines, where again, there is a risk of hematologic toxicities, lab monitoring, and so forth. The other red flag would be that…we don’t have any data yet, and it’s been [1.5] years since this DSMB study closure. I don’t want to assume nefarious sections or something else that is wrong with this. It may just be that everyone’s busy, which everyone is busy. But that is something I would want to see before using this more. My humble vote [is to] swipe left. With that, I’m happy to take questions. Thank you.
Transcript is AI generated and edited for clarity and readability.
