Table 6 Summary of data from key phase 3/randomized phase 2 studies of maintenance treatment post-induction in the nontransplant setting (data shown for overall treatment, including maintenance, and/or solely for maintenance phase where available).

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

Study

Treatment (maintenance dose/duration)

N

Follow-up

DoT

Key efficacy outcomes

Key safety and tolerability data

Myeloma XI25,40

R (10/25 mg, d 1–21, 28-d cycles, to PD) vs. observation post-CTD/CRD

407 vs. 316

31 monthsa

18 cycles (4-week cycles)a

Cumulative rate of response improvement at 60 months: 17.5% vs. 3.2%

Median PFS: 26 vs. 11 months (HR 0.44)

Median PFS2: 43 vs. 35 months (HR 0.72)

3-year OS: 66.8% vs. 69.8% (HR 1.02)

Grade 3/4 neutropenia: 28%/5%a

Discontinuations due to AEs: 28%a

SPMs: 5.3% vs. 3.1%a

MM-01572

MPR-R (10 mg, d 1–21, 28-d cycles, to PD) vs. MPR-placebo (d 1–21, 28-d cycles, to PD) vs. MP-placebo (d 1–21, 28-d cycles, to PD)

152 vs. 153 vs. 154

30 months

NR

Data from start of treatment:

ORR: 77% vs. 68% vs. 50%

 ≥ VGPR: 32.9% vs. 32.7% vs. 12.3%

Median PFS: 31 vs. 14 (HR 0.49) vs. 13 (HR 0.40) months

3-year OS: 70% vs. 62% vs. 66%

Post-induction:

Median PFS, MPR-R vs. MPR-placebo: 26 vs. 7 months (HR 0.34)

Data from start of treatment:

Grade 4 neutropenia: 35% vs. 32% vs. 8%

Grade 4 thrombocytopenia: 11% vs. 12% vs. 4%

Discontinuations due to AEs: 16% vs. 14% vs. 5%

SPMs: 7% vs. 7% vs. 3%

Post-induction, MPR-R arm:

Grade 4 neutropenia: 2%

Grade 4 thrombocytopenia: 6%

Grade 3/4 infection: 3%/2%

Discontinuations due to AEs: 8%

GIMEMA RV-MM-PI-20937

R (10 mg, d 1–21, 28-d cycles, to PD) vs. no maintenance post-MPR (n = 132) or ASCT (n = 141) consolidation

126 vs. 125

(59 vs. 57 post-MPR)

51.2 months from enrollment

NR

MPR-R vs. MPR:

Median PFS: 34.2 vs. 21.8 months

5-year OS: 70.2% vs. 58.7%

R maintenance CR rate improvement: 20.0% to 33.8%

R vs. no maintenance, post-MPR/ASCT

Median PFS: 41.9 vs. 21.6 months (HR 0.47)

OS: HR 0.64

R vs. no maintenance, post-MPR/ASCT

Grade 3/4 AEs:

Neutropenia 23.3% vs. 0%

Infections 6.0% vs. 1.7%

Dermatologic events 4.3% vs. 0%

Discontinuation due to AEs: 5.2% vs. 0%

HOVON87/NMSG1873

MPT-T (100 mg/d to PD) vs. MPR-R (10 mg, d 1–21, 28-d cycles, to PD)

318 vs. 319

36 months

T vs. R maintenance: median 5 vs. 17 months

ORR: 81% vs. 84%

≥ VGPR: 47% vs. 45%

Response improvement during maintenance: 23% vs. 18%

Median PFS: 20 vs. 23 months (HR 0.87)

4-year OS: 52% vs. 56% (HR 0.82)

Grade 3/4 neutropenia: 27% vs. 64%

Grade 3/4 thrombocytopenia: 8% vs. 30%

Grade 3/4 neuropathy: 16% vs. 2%

Discontinuation of maintenance due to AEs: 60% vs. 17%

SPMs: 7% vs. 6%

ECOG E1A0674

MPT-T (100 mg/d to PD) vs. mPR-R (10 mg, d 1–21, 28-d cycles, to PD)

154 vs. 152

40.7 months

15.6 vs. 14.9 months

13.5 vs. 13.3 months of maintenance

ORR: 63.6% vs. 59.9%

Median PFS: 21.0 vs. 18.7 months (HR 0.84)

Median OS: 52.6 vs. 47.7 months (HR 0.88)

Grade ≥ 3 nonhematologic:

Overall: 88% vs. 60%

Maintenance: 19% vs. 11%

Grade ≥ 4 hematologic:

Overall: 61% vs. 49%

Maintenance: 6% vs. 6%

Overall discontinuation of maintenance due to AEs: 41.8%

SPMs: 12.2% vs. 9.3%

NCT0109183141

RP (R 10 mg, d 1–21, 28-d cycles; P 50 mg, Q2d; to PD) vs. R alone post-CRD

57 vs. 49

41.0 vs. 42.3 monthsb

Median 28.9 vs. 25.3 monthsb

Data from enrollment (including CRD induction):

Median PFS: 24.2 vs. 27.6 months

4-year OS: 68% vs. 76%

Grade 3/4 AEs:b

Neutropenia: 8% vs. 13%

Infections: 8% vs. 5%

Discontinuations due to AEs: 5% vs. 8%

GEM05MAS6523,76

VMP vs. VTP induction

VT vs. VP maintenance (V 1.3 mg/m2 IV, d 1, 4, 8, 11, Q3M; T 50 mg/d; P 50 mg Q2d; up to 3 yrs)

130 vs. 130

91 vs. 87

72 months

(maintenance 38 months)

NR

VMP vs. VTP plus maintenance:

Median PFS: 32 vs. 23 months

Median OS: 63 vs. 43 months (HR 0.67); 77 vs. 54 months in patients receiving maintenance

Maintenance (VT vs. VP):

CR rate increased from 24% to: 46% vs. 39%

Depth of response improved in 19%

Median PFS: 39 vs. 32 months

5-year OS: 69% vs. 50%

Maintenance (VT vs. VP):

Grade 3/4 AEs: 17% vs. 5%

Grade 3/4 PN: 9% vs. 3%

Discontinuation due to AEs: 13% vs. 9%

GIMEMA-MM-03-0577

VMPT-VT (V 1.3 mg/m2 IV, Q2w; T 50 mg/d; up to 2 yrs) vs. VMP

254 vs. 257

23.2 months

82 patients received 6 months of VT

ORR: 89% vs. 81%

 ≥ VGPR: 59% vs. 50%

CR: 38% vs. 24%

3-year PFS: 56% vs. 41% (HR 0.67)

3-year TTNT: 72% vs. 60% (HR 0.58)

3-year OS: 89% vs. 87% (HR 0.92)

Response improvement during VT: ≥VGPR: 76% to 77%

CR: 58% to 62%

Grade 3/4 neutropenia: 38% vs. 28%

Grade 3/4 cardiologic AEs: 10% vs. 5%

Grade 3/4 sensory PN: 8% vs. 5%

Discontinuation due to AEs: 23% vs. 17%

VT maintenance:

Grade 3/4 AEs: 8%

Grade 3 PN: 4%

UPFRONT78

V (1.6 mg/m2 IV, d 1, 8, 15, 22, 35-d cycles; up to five cycles) post-Vd vs VTD vs. VMP

168 vs. 167 vs 167 (maintenance: 82 vs. 60 vs. 69)

42.7 months

Median 8 vs. 6 vs. 7 cycles

All five cycles of V maintenance: n = 53 vs. 43 vs. 53

ORR: 73% vs. 80% vs. 70%

 ≥ VGPR: 37% vs. 51% vs. 41%

Median PFS: 14.7 vs. 15.4 vs. 17.3 months

Median OS: 49.8 vs. 51.5 vs. 53.1 months

Maintenance:

Response improvement in 28 of 148 responding patients overall

Grade ≥ 3 AEs: 78% vs. 87% vs. 83%

Grade ≥ 3 PN: 22% vs. 27% vs. 20%

Maintenance:

New-onset grade ≥ 3 PN: 6% vs. 7% vs. 3%

HOVON-126/NMSG21#1386

Ixazomib (4 mg, d 1, 8, 15, 28-d cycles, to PD) vs. placebo post-ITd

143; 39 vs. 39

26.4 months

18.6 months from rdz

NR

Post-induction:

ORR: 81%; ≥ VGPR: 47%; CR: 9%

Median PFS: 14.3 months

18-month OS: 85%

From rdz:

Response improvement: 10% vs. 13%

Median PFS: 10.1 vs. 8.4 months

18-month OS: 100% vs. 92%

During induction:

8% PN

Discontinuations due to toxicity: 17%

During maintenance:

No new-onset PN with ixazomib

Discontinuations due to toxicity: 10% vs. 11%

ALCYONE22,87

Dara-VMP plus dara maintenance (16 mg/kg Q4w, with dex 20 mg, to PD) vs. VMP

350 vs. 356

Initial analysis: 16.5 months

14.7 vs. 12.0 months

ORR: 90.9% vs. 73.9%

 ≥ VGPR: 71.1% vs. 49.7%

CR: 42.6% vs. 24.4%

18-month PFS: 71.6% vs. 50.2% (HR 0.50)

Grade 3/4 infections: 23.1% vs. 14.7%

Dara infusion-related reactions: 27.7%

SPMs: 2.3% vs. 2.5%

   

Updated analysis: 27.8 months

 

 ≥ VGPR: 72.9% vs. 49.7%

CR: 45.1% vs. 25.3%

2-year PFS: 63% vs. 36% (HR 0.43)

2-year PFS2: 84.1% vs. 78.5%

Grade 3/4 infections: 25.1% vs. 14.7%

During dara maintenance:

Grade 3/4 AEs: 23.7%

  1. AEs adverse events, ASCT autologous stem cell transplant, CR complete response, CRD cyclophosphamide-lenalidomide-dexamethasone, CTD cyclophosphamide-thalidomide-dexamethasone, d day(s), dara daratumumab, dex dexamethasone, DoT duration of treatment, HR hazard ratio, ITd ixazomib-thalidomide-dexamethasone, IV intravenous, maint maintenance, MP melphalan-prednisone, (m)MPR(-R) (lower-dose) melphalan-prednisone-lenalidomide (plus lenalidomide maintenance), MPT(-T) melphalan-prednisone-thalidomide (plus thalidomide maintenance), NR not reported, ORR overall response rate, OS overall survival, P prednisone, PD progressive disease, PFS progression-free survival, PFS2 progression-free survival from start of treatment to progression on next line of treatment, PN peripheral neuropathy, Q2d every other day, Q2/4w every 2/4 weeks, Q3M every 3 months, R lenalidomide, rdz randomization, RP lenalidomide-prednisone, SPMs second primary malignancies, T thalidomide, TTNT time to next therapy, V bortezomib, Vd bortezomib-dexamethasone, VGPR very good partial response, VMP(T) bortezomib-melphalan-prednisone-(thalidomide), VP bortezomib-prednisone, VT bortezomib-thalidomide, VTD bortezomib-thalidomide-dexamethasone, VTP bortezomib-thalidomide-prednisone, yrs years.
  2. aOverall data in 1137 vs. 834 patients randomized to lenalidomide vs. observation across both the transplant-eligible and transplant-ineligible pathways.
  3. bOverall data in 117 vs. 106 patients randomized to lenalidomide-prednisone vs. lenalidomide maintenance across the CRD and ASCT consolidation arms.
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