Real-World Data Confirm KRd Safety, Efficacy in RRMM

A new analysis of the carfilzomib-lenalidomide-dexamethasone (KRd) regimen in patients with relapsed/refractory multiple myeloma (RRMM) shows that the therapy is effective in a real-world setting.

The new study, by Italian researchers, affirms earlier data derived in a clinical trial setting. The real-world results were published in the journal Hematological Oncology.

Corresponding author Elena Zamagni, MD, PhD, of the University of Bologna, and colleagues noted that the number of treatment options available to patients with MM has been growing substantially in recent years. Those options now include carfilzomib (Kyprolis), a second-generation proteasome inhibitor that is usually administered either with dexamethasone alone or with the immunomodulatory agent lenalidomide (Revlimid).

The ASPIRE trial showed that triplet therapy including carfilzomib (KRd) led to better outcomes than Rd, findings that were confirmed in an updated analysis of ASPIRE and in the ENDEAVOR study. However, the authors said while those data were robust enough to lead to carfilzomib’s approval for the treatment of RRMM in the United States and Europe, there remains a relative lack of data on the safety and efficacy of real-world patients, since many patients that might face the highest risk of adverse events were not eligible for inclusion in the trials.

The researchers decided to probe the real-world safety and efficacy of KRd by retrospectively analyzing the outcomes of 197 patients with RRMS who were treated at 6 Italian hematologic centers between January 2016 and March 2018.

About one-quarter (27%) of patients in the study had high-risk cytogenetic abnormalities, and the median number of prior lines of therapy in the group was 2, though the number of prior lines ranged from 1-8.

Ninety-six percent of patients had previously received bortezomib (Velcade), and 18% of those patients were refractory. Nearly half (45%) had previously received lenalidomide, and 22% of those patients were refractory.

At a median follow-up of 12.5 months, the overall response rate (ORR) to KRd was 88%, with a median progression-free survival (PFS) of 19.8 months and a 1-year overall survival (OS) rate of 80.6%.

More than half of patients (52%) had discontinued treatment at the median of 12.5 months, mostly due to progression (66%). Only 12% of patients discontinued due to toxicity.

A subgroup analysis showed patients with 2 or fewer lines of therapy had extended PFS and OS, as did patients who were not refractory to prior lenalidomide, those without high-risk cytogenetic abnormalities, and those who received very good partial responses or better.

“In conclusion, KRd demonstrated to be effective in RRMM patients treated in (a) real-world setting, without new safety concerns,” they wrote.

The most common grade 3-4 adverse events were neutropenia, infections, and hypertension, which affected 21%, 11%, and 6% of patients, respectively.

Zamagni and colleagues wrote that the data show a good safety profile for KRd, though they noted that the risk of cardiovascular adverse events remains a poorly understood but important issue, particularly for patients over the age of 75. The authors said they identified patients with cardiovascular risk prior to the start of treatment, and monitored their blood pressure closely.

The investigators closed by saying these real-world data confirm that KRd is a good option for many patients, with an advantage over lenalidomide and dexamethasone alone.

Reference

Rocchi S, Tacchetti P, Pantani L, et al. A real-world efficacy and safety analysis of combined carfilzomib, lenalidomide and dexamethasone (KRd) in relapsed/refractory multiple myeloma. Hematol Oncol. Published online October 21, 2020. doi:10.1002/hon.2820