Biochemical vs Clinical Progression in Relapsed/Refractory Multiple Myeloma

EP: 1.Team Introductions: MM Experts From UT Southwestern vs Mayo Clinic

EP: 2.Relapsed/Refractory Multiple Myeloma: The KarMMa-3 Study

EP: 3.Cross Q&A: Idecabtagene Vicleucel in Relapsed/Refractory Multiple Myeloma

EP: 4.Relapsed/Refractory Multiple Myeloma: The CARTITUDE-4 Study

EP: 5.Cross Q&A: Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma

EP: 6.Relapsed/Refractory Multiple Myeloma: The ALLIANCE A061202 Study

EP: 7.Cross Q&A: Isatuximab + Pom-Dex in Relapsed/Refractory Multiple Myeloma

EP: 8.Relapsed/Refractory Multiple Myeloma: The IKEMA Study

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EP: 9.Biochemical vs Clinical Progression in Relapsed/Refractory Multiple Myeloma

EP: 10.Cross Q&A: Isa + KD in Relapsed/Refractory MM and Biochemical vs Clinical Progression

EP: 11.Mayo Clinic and UT Southwestern “Face Off” Over Multiple Myeloma and CML

Transcript:

Wilson Gonsalves, MD: I’m going to switch gears completely and jump onto the next. This isn’t an abstract, it’s a paper that was originally an abstract likely at [an American Society of Hematology meeting], and it is A retrospective study from a group here at Mayo Clinic entitled, “Outcomes After Biochemical or Clinical Progression in Patients with Multiple Myeloma” by [Sarah] Goldman-Mazur and Shaji Kumar, who led this study. So, just some background on why this study was even done. With all the abstracts we have been reviewing, we’ve seen most patients with multiple myeloma eventually relapse. You can take relapses and put them in 2 buckets. They’re either biochemical asymptomatic relapses or biochemical progressions, or those with clinical progressions, those who end up with any of those CRAB features [hypercalcemia, renal dysfunction, anemia and bone lesions]. It’s been known that there’s a difference in terms of the prevalence of how these patterns of progression exist. A lot of that has been taken out of clinical trial data, which may not always reflect our clinical patient population that we treat. As such, there have been various other smaller studies that have been done from various other institutions looking at the patterns of relapse, biochemical vs clinical progressions. Here, the full goal was to better understand over the last 2 decades, per se, what [were] our progression patterns and how did this impact outcomes. The primary objective of the study was to describe the prevalence in outcome of biochemical progression vs clinical progression in the real-world settings, outline the various percentages of how patients present with different CRAB symptoms at diagnosis and at relapse, and then try to take a step back and see, [is] there anything at baseline that could help one clinically predict what the pattern of relapse would be like?

I’ll quickly run through methods. So, just key things, this is a relapsed myeloma population dating back from 2001 to 2018, so you had to be 18 years or older, you needed to have at least one disease relapse and requiring an additional line of therapy, and you needed to know the pattern of relapse and the reason for the purpose of studies; if you didn’t know what happened to them at the time of relapse, they were not included in this group. Of this just some key features, what you define as clinical progression here. You needed to have CRAB symptoms, so basically, an increase if you had a plasmacytoma, soft tissue lesion increase by 50% or more of the plasmacytoma or bone lesion, presence of hypercalcemia defined by 11.5 or higher, a decrease in hemoglobin by more than 2 points, or less than 10 g/dL, or an increase in creatinine over 2 mg/dL or hyperviscosity. There was a small subset that they looked at, and they considered within the clinical progression group who had aggressive relapse where, clinically, we would probably all agree that somebody presenting with extramedullary disease, plasma cell leukemia, or hyperviscosity requiring plasmapheresis would be those aggressive-type relapses. Again, a big chart, I’m just going to summarize 3 things, which one could probably guess that are likely going to be associated if these were the clinical characteristics of the entire population. The middle column and the column to the right are basically the baseline characteristics of the biochemical progression and the clinical progression. Three things I’ll highlight is just as you would predict the clinical progression, folks have just aggressive features and diagnosis. Here, we tend to use the S phase, which is more of a reflection of the proliferation rate. Clinical progressors with more aggressive disease at baseline had a higher S phase defined by 2% or more, and they were more likely to have non-secretory disease and to have extramedullary disease at diagnosis. Just looking at the numbers, what were the patterns of relapse of this particular population of 18 years? The majority of patients, like 60 to 40, tend to have biochemical-type progressions, and the other 40% had clinical progressions. Most of these clinical progressions were mainly new bone lesions that would arise. A small group of these patients had aggressive relapses, and within that group most of them were extramedullary disease rather than plasma cell leukemia, or hyperviscosity, which I would imagine would be more of those IgM [immunoglobulin M]-type patients on there. I think this table was, again, something that was pretty practical, and if you could look at what the baseline presentation of CRAB symptoms were, the same presentation at first relapse would almost mirror that. If you presented with renal insufficiency as one of your CRAB symptoms at diagnosis, you are more likely to have that presentation at relapse. Same thing for anemia; interestingly, if you had anemia at diagnosis, you are also more likely to have renal insufficiency at relapse, but less likely to have bone disease, and it was the opposite when we looked at bone disease; you’re more likely to progress at bone disease and less likely to have renal disease and anemia.

In terms of outcomes for time to next therapy and overall survival? Now, again...you would think that the folks with biochemical progressions, generally, there is something about them with better disease biology; they have a far better time to next therapy as well as an overall survival compared [with] those patients who have clinical progression. The ones with clinical progression who have those aggressive features have the worst outcomes for time to next therapy and overall survival. Finally, what were some predictors if you were seeing a patient who could help you decide, is this person at high risk of presenting clinically? Again, there were features that we would expect if somebody presented with extramedullary disease; you probably should be watching for those clinical progressions with extramedullary disease. Same thing, if they had very high labeling index at diagnosis, they were more likely to have a clinical relapse. I think something over here in the very second last line, if you had a pretty deep response of a [very good partial response] or better, maybe you are less likely to have a clinical relapse, but I’m not sure that does it justice because you can’t answer that in a controlled fashion per se. In summary, this paper outlines some things that we know and we expected but puts numbers to it. If you have clinical progressions at first relapse, you have inferior post-progression outcomes. Clearly, the pattern of presentation and diagnosis is likely going to predict the pattern of presentation at first relapse. Hopefully, this sets the stage where we can truly understand who’s at risk for those clinical progression, and I think a more interesting question will be, when you do biochemically progress, and does it matter when you initiate therapy, which I think is a question all of us probably handle clinically on a case-by-case basis, per se. With that, that was the end of my presentations.

Judy Schreiber, PhD, RN: Thank you so much, Dr Gonsalves, thank you for both those presentations; it’s very interesting data.

Transcript edited for clarity.