Patients With Relapsed/Refractory MM More Likely to Have Sustained MRD on Daratumumab

Minimal residual disease (MRD) is a strong prognosticator of cancer outcomes, and recent research found that patients with relapsed/refractory multiple myeloma (MM) are more likely to achieve MRD on daratumumab than on a standard of care alone.

Daratumumab combined with standard of care in patients with relapsed/refractory multiple myeloma (RRMM) enables more patients to achieve minimal residual disease (MRD) negativity, which is associated with prolonged survival.

A study presented at the 60th American Society of Hematology Annual Meeting & Exposition evaluated sustained MRD negativity in more than 1000 patients with RRMM treated with daratumumab plus standard of care. The patients were taken from the POLLUX and CASTOR studies, which are open-label, multicenter, randomized (1:1), active-controlled phase 3 studies in patients with RRMM who have received at least 1 prior line of therapy.

MRD is being investigated as a surrogate for end points like overall survival, the authors explained.

“When measured sequentially, sustained MRD-negativity provides an index of deep clinical responses that may provide a more robust assessment of disease control,” they wrote.

Patients either received standard of care treatment alone or standard of care plus daratumumab. In POLLUX, all patients also received lenalidomide (days 1 to 21 in a 28-day cycle) and dexamethasone (once a week). In CASTOR, all patients also received bortezomib (days 1, 4, 8, and 11 for eight 21-day cycles) and dexamethasone (days 1, 2, 4, 5, 8, 9, 11, and 12).

MRD was assessed when complete response (CR) was suspected and again at the 3- and 6-month follow-up after confirmed CR in the POLLUX study; it was assessed at suspected time of CR and then 6 and 12 months after the first treatment in CASTOR.

There were 569 patients with a median follow-up duration of 39.5 months in POLLUX and 498 patients with a median follow-up duration of 31.3 months in the CASTOR trial. The authors found that more patients achieved sustained MRD at or past 6 months when they were treated with daratumumab than without in both trials. In both trials, approximately 30% of patients receiving daratumumab as part of their treatment regimen had sustained MRD negativity compared with 3% who did not receive daratumumab in POLLUX and 13% in CASTOR.

At or past 12 months, 13% of daratumumab patients in POLLUX and 3% in CASTOR had sustained MRD negativity compared with 0.4% and 0%, respectively, of patients who received standard of care without daratumumab.

“Importantly, the ability to reach durable MRD negativity is associated with prolonged survival, suggesting that achieving durable MRD negativity should be a treatment goal for RRMM [patients],” the authors wrote.

References

Avet-Loiseau H, San-Miguel JF, Casneuf T, et al. Evaluation of sustained minimal residual disease (MRD) negativity in relapsed/refractory multiple myeloma (RRMM) patients (pts) treated with daratumumab in combination with lenalidomide plus dexamethasone (D-Rd) or bortezomib plus dexamethasone (D-Vd): analysis of Pollux and Castor. Presented at: 60th American Society of Hematology Annual Meeting & Exposition; December 2, 2018; San Diego, CA. Abstract 3272.