At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, Stefan Knop, Wuerzburg University Medical Center, Wuerzburg, Germany presented initial results from a randomized phase 3 study of triplet vs quadruplet therapeutic regimen for patients with newly diagnosed transplant-eligible multiple myeloma (MM).

Transcript:

Hello, we are here at ASCO 2023 in Chicago. My name is Stefan Knop, I'm from Wuerzburg University Medical Center in Wuerzburg, Germany. Here we presented the initial results from a randomized phase 3 study in transplant-eligible multiple myeloma. 

We compared a quadruplet regimen of elotuzumab, carfilzomib, lenalidomide and dexamethasone (Elo-KRd) versus carfilzomib, lenalidomide, and dexamethasone (KRd) in patients who were deemed transplant-eligible, and were newly diagnosed with multiple myeloma. 

The first coprimary endpoint was the proportion of patients who are in [International Myeloma Working Group] (IMWG)-VGPR and at the same time being [minimal residual disease] MRD-negative, so tested negative for minimal residual disease done by EuroFlow cytometry, of the sensitivity of 10^-5. We choose KRd as a comparator due to the fact that it's much more tolerable than VRd [bortezomib, lenalidomide and dexamethasone], causing less peripheral neuropathy.

The hypothesis was that we could increase the rate of VGPR and better, along with MRD negativity, coming from a historic 16% and we deemed an increase of 2/3s, landing somewhere around 26% as clinically relevant. With this hypothesis, 576 patients will be needed. Between August 2018 and October 2021, 579 patients were randomized. And as we run into the first wave of the pandemic, I will present some data affecting patients from COVID-19 later on.

When it comes to patient characteristics, the median age was around 58 years of age, so relatively young cohort, as it's always done in transplant-eligible patients. Roughly 24% of patients had high-risk molecular cytogenetics defined by the presence of either additional copies of one 1q21, deletion 17p, translocation (4;14), or translocation (14;16). The rate of patients in R-ISS [stage] III was roughly 10%, and the proportion of patients in conventionally measured ISS [stage] III around 20%.

The first co-primary endpoint was met, showing an approximately 15% higher rate of patients being in VGPR plus MRD-negative in the experimental arm, Elo-KRd versus KRd. And also the KRd arm reached a combined rate of approximately 35%, which is significantly higher incidence than what we initially assumed, being around 26%. 

When we concentrate on the cohort being in VGPR and MRD-negative, we see no difference in stringent [complete response] (CR) and CR, but we see 15% higher rate of patients being in VGPR. When it comes to MRD testing, roughly 86% of patients were evaluable and were evaluated for MRD. Again, we can see a much higher rate of patients in MRD-negative status irrespective of the IMWG response when compared to KRd.

In terms of treatment-emergent adverse events, we saw slightly higher rate of febrile neutropenia and thrombocytopenia of grades 3 and 4 in the experimental versus the standard arm. We saw some incidences of cardiotoxicity above 2.5%, we saw less than 2% renal failure of grades 3/4, and we saw virtually no high rates, so grade 3 and higher peripheral neuropathy, what is in line with earlier results employing KRd as a treatment regimen.

In conclusion, we have conducted one of the largest carfilzomib upfront studies so far, specifically in transplant-eligible multiple myeloma. We see that patients are in better higher quality response with Elo-KRd versus KRd, already at the cut after only 6 cycles of induction therapy. We see no new safety signals. 

And of course, the follow-up of the study is ongoing, specifically to evaluate the second co-primary endpoint, which is 3-year PFS. And of course, we are excited to see whether this early advantage favoring E-KRd versus KRd will also transform into a better 3-year PFS later on. Thank you very much for your interest and for your attention.

Source:

Knop S, Stuebig T, Kull M, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus elotuzumab and KRd in transplant-eligible patients with newly diagnosed multiple myeloma: Post-induction response and MRD results from an open-label randomized phase 3 study. Presented at ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 8000.