Source: Myeloma – Hematology Advisor

Including daratumumab in second-line therapy improves outcomes in patients with multiple myeloma (MM), even those who relapse less than 2 years after initial therapy, according to research published in Blood Advances.

These results come from a post hoc analysis of 2 phase 3 trials — CASTOR (ClinicalTrials.gov identifier: NCT02136134) and POLLUX (ClinicalTrials.gov identifier: NCT02076009).

The pooled patient population included 240 patients with early relapse (less than 2 years from the start of first-line therapy) and 290 patients with late relapse (2 years or more from the start of first-line therapy).

In the early-relapse group, 125 patients received daratumumab in combination with either bortezomib and dexamethasone (Vd) or lenalidomide and dexamethasone (Rd), and 115 patients received Vd or Rd without daratumumab.

In the late-relapse group, 146 patients were assigned to daratumumab plus Vd or Rd, and 144 patients were assigned to Vd or Rd without daratumumab.

The median follow-up in the intent-to-treat population was 72.6 months in the CASTOR trial and 79.7 months in POLLUX.

All efficacy outcomes — overall response rate (ORR), complete response (CR) rate, minimal residual disease (MRD) negativity rate, progression-free survival (PFS), and overall survival (OS) — were significantly better for the daratumumab recipients, regardless of the timing of relapse.

Among patients with early relapse, the ORR was 90.9% in the daratumumab group and 73.6% in the control group (P =.0004). Among patients with late relapse, the ORR was 93.8% and 80.9%, respectively (P =.001).

The CR rate among patients with early relapse was 46.3% in the daratumumab group and 13.6% in the control group (P <.0001). Among patients with late relapse, the CR rate was 57.2% and 29.8%, respectively (P <.0001).

The MRD negativity rate among patients with early relapse was 22.4% in the daratumumab group and 2.6% in the control group (P <.0001). Among patients with late relapse, the MRD negativity rate was 31.5% and 10.4%, respectively (P <.0001).

The median PFS among patients with early relapse was 27.9 months in the daratumumab group and 10.0 months in the control group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P <.0001). For patients with late relapse, the median PFS was 51.8 months and 14.4 months, respectively (HR, 0.35; 95% CI, 0.26-0.47; P <.0001).

The median OS among patients with early relapse was 65.0 months in the daratumumab group and 38.2 months in the control group (HR, 0.62; 95% CI, 0.45-0.86; P =.0036). Among patients with late relapse, the median OS was not reached and 67.3 months, respectively (HR, 0.67; 95% CI, 0.48-0.93; P =.0183).

“These results, combined with previous subgroup analyses of CASTOR and POLLUX, show that daratumumab-containing regimens maintain consistent clinical benefits for patients with high-risk RRMM [relapsed/refractory MM], as defined either by cytogenetics or by early progression/relapse,” the researchers concluded.

Disclosures: CASTOR and POLLUX were supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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