Table 5 Summary of data from key phase 3 studies of continuous therapy in the nontransplant setting.

From: Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma

Study

Treatment

N

Follow-up

DoT

Key efficacy outcomes

Key safety and tolerability data

FIRST4,64

Continuous Rd vs. Rd (18 cycles) vs. MPT (72 weeks)

535 vs. 541 vs. 547

Initial analysis: 37.0 mos

Median: 18.4 vs. 16.6 vs. 15.4 mos

ORR: 75% vs. 73% vs. 62%

 ≥ VGPR: 43% vs. 42% vs. 28%

Median PFS: 25.5 vs. 20.7 vs. 21.2 mos (HR 0.70 vs. Rd18/0.72 vs. MPT)

4-yr OS: 59% vs. 56% vs. 51% (HR 0.90 vs. Rd18/0.78 vs. MPT)

Grade 3/4 AEs: 85% vs. 80% vs. 89%

Grade 3/4 infection: 29% vs. 22% vs. 17%

SPMs: 3% vs. 6% vs. 5%

   

Updated analysis: 67 mos

Mean: 25.5 vs. 12.6 vs. 11.9 mos

ORR: 81% vs. 79% vs. 67%

 ≥ VGPR: 48% vs. 47% vs. 30%

4-yr PFS: 32.6% vs. 14.3% vs. 13.6% (HR 0.70/0.69)

Median OS: 59.1 vs. 62.3 vs. 49.1 mos (HR 1.02/0.78)

Grade 3/4 infection: 32% vs. 22% vs. 17%

SPMs: 7% vs. 7% vs. 9%

SWOG S077769,70

VRd-Rd vs. Rd

(Rd to PD)

264 vs. 261

Initial analysis: 54 vs. 56 mos

NR

ORR: 82% vs. 72%

 ≥ VGPR: 43.5% vs. 31.8%

Median PFS: 43 vs. 30 mos (HR 0.712)

Median OS: 75 vs. 64 mos (HR 0.709)

Grade 3/4 AEs: 82% vs. 75%

Grade ≥ 3 neurotoxicity: 33% vs. 11%

Discontinuation due to AEs: 23% vs. 10%

SPMs: 4% vs. 4%

   

Updated analysis: 84 mos

17.4 mos (Rd post-induction)

 ≥ VGPR: 74.9% vs. 53.7%

Median PFS: 41 vs. 29 mos (HR 0.742)

Median OS: not reached vs. 69 mos (HR 0.709)

SPMs: 8% vs. 7%

RV-MM-PI-075267

Rd-R vs. continuous Rd

98 vs. 101

25 mos

NR

ORR: 73% vs. 63%

 ≥ VGPR: 43% vs. 35%

Median EFS: 9.3 vs. 6.6 mos (HR 0.72)

Median PFS: 18.3 vs. 15.5 mos (HR 0.93)

18-mo OS: 85% vs. 81% (HR 0.73)

Dose reductions (9 cycles):

R: 1% vs. 21%

Dex: 17% vs. 29%

MAIA68

Dara-Rd vs. Rd

368 vs. 369

28 mos

25.3 vs. 21.3 mos

≥ VGPR: 79.3% vs. 53.1%

≥ CR: 47.6% vs. 24.9%

Median PFS: not reached vs. 31.9 mos (HR 0.56)

OS: 16.8% vs. 20.6% of patients had died; median not reached on either arm

Common grade 3/4 AEs: neutropenia (50.0% vs. 35.3%), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), pneumonia (13.7% vs. 7.9%)

Infections: any-grade, 86.3% vs. 73.4%, grade 3/4 32.1% vs. 23.3%

Infusion-related reactions (Dara-Rd): 40.9% (2.7% grade 3/4)

Discontinuation due to AEs: 7.1% vs. 15.9%

  1. AE adverse event, CR complete response, dara daratumumab, dex dexamethasone, DoT duration of treatment, EFS event-free survival, HR hazard ratio, mos months, MPT melphalan-prednisone-thalidomide, NR not reported, ORR overall response rate, OS overall survival, PD progressive disease, PFS progression-free survival, R lenalidomide, Rd lenalidomide-dexamethasone, SPM second primary malignancy, SWOG Southwest Oncology Group, VGPR very good partial response, VRd bortezomib-lenalidomide-dexamethasone.
Back to article page