Once-Weekly KRd Shows Promise in Newly Diagnosed MM

Triplet combination therapy is an increasingly common treatment option for patients with newly diagnosed multiple myeloma (NDMM), but a new study suggests a common regimen can be administered successfully in once-weekly doses instead of twice-weekly.

Many patients with NDMM are given the second-generation proteasome inhibitor carfilzomib (Kyprolis), along with the immunomodulatory agent lenalidomide (Revlimid) and dexamethasone, or KRd. Typically, the triplet therapy is administered on a twice-weekly basis.

Corresponding author Melissa Alsina, MD, of Moffit Cancer Center in Florida, and colleagues wanted to know whether the therapy could instead be given once a week, something that would be significantly more convenient for patients receiving the therapy. They reported their findings in the American Journal of Hematology.

In the study, carfilzomib was administered on days 1, 8, and 15 along with 40-mg doses of dexamethasone. Lenalidomide was administered at a dose of 25 mg on days 1 through 21. Initially, a dose-expansion arm of 9 patients was given carfilzomib at 20/70 mg/m² (20 mg/m_² on cycle 1, day 1, and 70 mg/m² thereafter). That arm was suspended, however, due to serious adverse events.

Next, another 9 patients were treated on a 2-step-up KRd dosing schedule (20/56 mg/m²), after which a new dose-expansion arm of carfilzomib 56 mg/m² was recommended.

The results for 33 patients were reported. The rate of grade 3 or higher treatment-emergent adverse events was 63.6%.

Twenty-five patients underwent stem cell collection, 18 of whom eventually underwent autologous stem cell transplantation, and 5 of whom resumed on-study KRd following transplantation.

There was an overall response rate (ORR) by cycle 4 of 97%, using the benchmark of very good partial response (VGPR) or better among those in the 20/56-mg/m² group.

Among the 15 patients who did not receive stem cell transplant, the median number of cycles was 16.0, and the ORR was 93.3%. At the median follow-up of 8.1 months, median progression-free survival was not reached, Alsina and colleagues wrote.

In their discussion, they noted that they had previously found success with once-weekly KRd regimens in patients with relapsed or refractory MM (RRMM).

“Consistent with results reported in RRMM, once-weekly KRd (carfilzomib 56 mg/m²) was active and well-tolerated in patients with NDMM,” Alsina and colleagues said.

The authors added that the superior tolerability for the 56-mg/m² dose among patients with NDMM was similar to what they found in RRMM. These data show that most patients were still able to undergo successful stem cell collection and transplantation without any adverse effects as a result of the KRd regimen. This finding matches what they found with the standard twice-weekly KRD (carfilzomib 36 mg/m²).

They, however, that they were unable to compare patients in high-risk and standard-risk categories due to the small sample size.

As the current study was a phase 1b study, Alsina said further investigation is needed; however, they said these data are promising.

“Although not powered for efficacy, rates of overall response and ≥VGPR in this study were similar to those of other frontline KRd studies,” the authors concluded. “These results support the use of once-weekly KRd regimen in patients with NDMM.”

Reference:

Alsina, M, Landgren O, Raje N, et al. A phase 1b study of once‐weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma. Am J Hematol. Published online October 30, 2020. doi:10.1002/ajh.26041