Amid the recent increase in the use of lenalidomide in the initial treatment of multiple myeloma, additional evidence suggests that the DKd (daratumumab/carfilzomib/dexamethasone) three-drug regimen could be the most effective first-line treatment for relapsed or refractory patients.

The Korean insurance authorities are reviewing the reimbursement of DKd therapy on the condition that patients pay 100 percent (100/100) of the cost of Darzalex (daratumumab), an anti-CD38 monoclonal antibody, drawing attention from parties involved to see if the treatment environment for relapsed and refractory patients in this country will change.

Recently, the international journal Leukemia & Lymphoma published the results of a matching-adjusted indirect comparison (MAIC) between DKd, PVd (pomalidomide/bortezomib/dexamethasone) and DPd (daratumumab/pomalidomide/dexamethasone) regimens.

Lenalidomide, a type of immunomodulatory imide drug (IMiD), is increasingly used in frontline settings as initial induction therapy, post-transplant consolidation, and as part of maintenance therapy. Given that lenalidomide treatment is typically administered until the disease progresses or the patient becomes intolerant to treatment, most patients become refractory to lenalidomide after initial treatment.

These relapsed-refractory patients are not candidates for lenalidomide-based triplets in their next treatment, and there is a need to find more effective treatments for the growing number of lenalidomide-refractory patients.

Therefore, the researchers conducted an indirect comparative evaluation of DKd, PVd, and DPd regimens as treatment options in the event of relapse or failure in lenalidomide-exposed patients.

MAIC goes beyond traditional indirect comparisons that utilize summary data and uses individual patient-level data (IPD) to make comparisons adjusted for study arm characteristics.

The researchers utilized the respective landmark trials CANDOR (DKd regimen), OPTIMISMM (PVd regimen), and APOLLO (DPd regimen) to evaluate the indirect comparisons of the three.

First, they indirectly compared the outcomes of the DKd regimen arm (123 patients) exposed to lenalidomide in the CANDOR study with the outcomes of the PVd regimen arm (281 patients) in the OPTIMISMM study.

Before the matching, there were significant differences between the two groups in the shares of patients who were "75 or older," "had prior bortezomib exposure," "were refractory to bortezomib," "marked ECOG PS score of 0," "were refractory to lenalidomide," and "received two or more prior therapies." After the matching, however, the baseline characteristics were balanced.

In the matched patient group, 24-month progression-free survival (PFS) was 48.5 percent for the DKd therapy and 28.8 percent for the PVd therapy. The hazard ratio (HR) for PFS was 0.60 in favor of the DKd therapy.

The incidence of grade 3 or higher neutropenia was lower in the DKd arm, but the incidence of grade 3 or higher anemia and thrombocytopenia was slightly higher in the DKd arm.

The researchers also indirectly compared the results of the same patient group in the CANDOR trial with the results of the DPd regimen (151 patients) in the APOLLO trial. Before matching, there were significant differences in several categories, including the proportion of patients "75 years or older" and "proteasome inhibitor refractory," but after matching, baseline characteristics were balanced.

PFS at 24 months after matching was 47.4 percent in the DKd arm and 36.6 percent in the DPd arm, which was numerically higher but not statistically significant, with a PFS hazard ratio (HR) of 0.77 in favor of the DKd regimen. Adverse event differences were similar to previous comparisons with PVd regimens.

"Our estimates suggest that DKd may be a highly effective lenalidomide-sparing treatment option for first relapse, especially given the increasing number of patients who have received lenalidomide as part of their first-line treatment," the researchers wrote in the paper. "We also found that adding an anti-CD38 monoclonal antibody, such as daratumumab, to the existing standard of care has demonstrated favorable efficacy in a growing number of clinical trials."

As the efficacy of the DKd triple therapy continues to grow, the Korean insurance authorities have also begun to review its reimbursement.

Amgen's DKd reimbursement application passed the Cancer Disease Review Committee in April and is now in the Pharmaceutical Reimbursement Evaluation Committee’s subcommittee.

Amgen requests that Darzalex be covered as a patient-payment option in addition to the existing Kd double regimen.

If approved, relapsed and refractory patients in Korea will soon be able to use Darzalex for first-line treatment at full patient payment (100/100) and Kd at partial patient payment (5/100) as they do now.