Noopur Raje, MD, Massachusetts General Hospital, Boston, MA shares findings from the Phase II KarMMa study (NCT03361748) of idecabtagene vicleucel (ide-cel) in high-risk subgroups of patients with relapsed/refractory (R/R) multiple myeloma (MM). Ide-cel is a BCMA-targeting CAR T-cell therapy, shown in the KarMMa trial to give deep and durable responses in the overall R/R MM cohort. Patients were then risk-stratified; high-risk characteristics included extramedullary disease, high-risk cytogenetics, high tumor burden, and R-ISS stage III disease at baseline. The overall response rates and complete response rates were ≥65% and ≥20%, respectively, in all high-risk subgroups except those with R-ISS disease stage III. Extramedullary disease and high-tumor burden did not substantially impact these outcomes. Similar exceptions were seen in the duration of response measurements, with only R-ISS stage III disease having a substantial negative impact. The results suggest ide-cel is of significant benefit, even in most of these difficult to treat patients. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
Transcript (edited for clarity)
We’re presenting data on the KarMMa trial, and we’ve done a subgroup analysis focusing on the high-risk patient population in this KarMMa trial, which was presented at ASCO. As you all remember, this was a total of 128 patients, and at least a third of these had high-risk features. And the way we defined high-risk was, high-risk by cytogenetics, high risk by tumor burden, higher risk by RISS staging, and also included extramedullary disease...
We’re presenting data on the KarMMa trial, and we’ve done a subgroup analysis focusing on the high-risk patient population in this KarMMa trial, which was presented at ASCO. As you all remember, this was a total of 128 patients, and at least a third of these had high-risk features. And the way we defined high-risk was, high-risk by cytogenetics, high risk by tumor burden, higher risk by RISS staging, and also included extramedullary disease. And nearly half these patients had one or all of these features. And we looked to see whether or not the responses in this patient population was any different. When we looked at this data in our subgroup analysis, what we found was the response rates was pretty comparable to the rest of the patients. So not a big difference in terms of response rates, except in the RISS group.
Now, the RISS group includes patients with high-risk disease, as well as high-risk cytogenetics. And outside of that, all of them had an overall response rate of more than 65%. And even those with the presence of extramedullary disease actually had an extremely high response rate. CR rates in the majority of patients was in excess of 20% in this patient population. Again, underscoring the fact that idecabtagene vicleucel is a treatment strategy, which can absolutely be used and should in fact, be specifically used in this very difficult to treat high-risk patient population. Now based on the KarMMa trial, based on the fact that we’d really enriched for this high-risk patient population. We do have two ongoing trials looking at high-risk disease. Specifically, we have an ongoing trial called KarMMa-2. These are patients who are progressing either after a transplant or within 18 months of the induction treatment with evidence of high-risk cytogenetic features.
And they’re getting CAR T-cells early on as a second line of treatment in the context of myeloma. The other clemency trial, which we’re doing in the context of high-risk disease is upfront. So if you have cytogenetics, which portend a high-risk features such as the 4;14, 14;16 translocation, or the p53 deletion or mutation at the time of diagnosis, you can actually get CAR T-cells instead of getting an autologous stem cell transplant. So these are ongoing trials and we’ll validate what we’ve seen in the KarMMa subgroup analysis of efficacy and improvement in duration of response, as well as progression free survival in patients with high risk, multiple myeloma.