MANHATTAN: Daratumumab-Based Quadruplet for MM Leads to MRD Negativity

Daratumumab-based quadruplet regimens are safe and effective for newly diagnosed multiple myeloma (MM), according to results of the MANHATTAN trial.

MANHATTAN was a non-randomized study of 41 patients with newly diagnosed MM treated at the Memorial Sloan Kettering Cancer Center. Patients received a combination of carfilzomib 20/56 mg/m2, lenalidomide 25 mg, dexamethasone 40 mg, plus daratumumab 16 mg/kg for eight cycles. Median follow-up was 20.3 months. The primary endpoint was the minimal residual disease (MRD) negativity rate without high-dose melphalan chemotherapy and autologous hematopoietic cell transplant. Secondary endpoints included safety, efficacy, and survival.

Overall, 29 patients (71%; 95% confidence interval 54-83) achieved MRD negativity. Median time to MRD negativity was six cycles. All patients responded to treatment, and 95% achieved at least a very good partial response. The most common grade 3 or 4 adverse events, occurring in two or more patients, were neutropenia, rash, lung infection, and increased alanine aminotransferase level. No patients died on the trial.

“In this non-randomized clinical trial of patients with newly diagnosed MM, [carfilzomib-lenalidomide-dexamethasone-daratumumab] combination therapy was associated with unprecedented high rates of MRD negativity by itself,” wrote the researchers in conclusion. “Building on these promising results, we have developed a large randomized multicenter clinical trial (ADVANCE) comparing [this regimen] with current standard of care for patients with newly diagnosed MM, and the trial has already opened for enrollment.”

These findings were published in JAMA Oncology.