Evaluating the combined daratumumab, lenalidomide and dexamethasone therapy for patients with multiple myeloma, based on frailty levels.

This study compared the effectiveness and safety of using daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone (Decadron)(D-Rd) to lenalidomide and dexamethasone (Rd) treatment in patients with newly diagnosed multiple myeloma (NDMM), based on frailty levels. The data showed that D-Rd was more effective than Rd at improving progression-free survival in these patients, regardless of frailty level after 3 years.

Multiple myeloma (MM) is a blood cancer that originates from blood cells called plasma cells. Patients with NDMM are normally treated with chemotherapy and a stem cell transplant. Elderly patients or those with certain conditions are commonly not eligible for a transplant and require different combination therapies.

Daratumumab is an immunotherapy used either on its own or combined with standard-of-care for patients with NDMM. Daratumumab works by directly targeting and killing cancer cells. Lenalidomide, an immunotherapy, boosts the immune system and assists in destroying cancer cells. Dexamethasone, a steroid, reduces swelling and inflammation, and decreases pain and pressure. A combination of these three therapies was previously shown to provide a progression-free survival (PFS) benefit and deeper responses in patients with NDMM, including the elderly. However, data analysis from this study did not consider fitness levels (frailty status), based on age. There is a need to determine the effectiveness of this combination therapy in elderly patients based on frailty levels.

This study included 737 patients with NDMM. 368 patients were randomly assigned to a D-Rd treatment group and 369 patients to Rd treatment. Patients were classified as non-frail (fit and intermediate) and frail. 396 patients were classified as non-frail, with 146 fit patients and 250 intermediate patients. Of the fit patients, 68 patients had D-Rd and 78 patients received Rd. 128 intermediate patients received D-Rd and 122 intermediate patients had Rd. 341 patients were classified as frail, with 172 patients having received D-Rd and 169 patients treated with Rd. The average follow-up time was 36.4 months.

After 36.4 months, non-frail patients had a longer survival without cancer worsening compared to those that were frail. However, patients in the D-Rd group in all subgroups had better survival without cancer worsening compared to those in the Rd group. In the non-frail group, patients treated with D-Rd had a 52% higher survival without cancer worsening compared to those in the Rd group. In the frail group, patients treated with D-Rd had a 38% better survival without cancer worsening compared to those in the Rd group. 

Also, patients treated with D-Rd in all subgroups had better rates of complete response (disappearance of cancer) and minimal residual disease (a very low number of cancer cells left after treatment) compared to those treated with Rd.

The most common side effect of D-Rd therapy was a low white blood cell count (45.4% in the non-frail group versus 57.7% in the frail group).

The study concluded that combined therapy with daratumumab, lenalidomide, and dexamethasone provided evidence of clinical benefit to patients with NDMM and was not affected by frailty levels.

The study assessed frailty based on records from a past study, so there may be missing data. Frailty score calculations were somewhat subjective. This study was funded by Janssen, the manufacturer of daratumumab.