Maintenance therapy (lenalidomide, ixazomib, and daratumumab alone or in combination)

The prospective randomized AURIGA trial (NCT03901963) included 200 patients with newly diagnosed multiple myeloma who achieved a very good or better partial response, were MRD-positive on bone marrow (10-5), and who had not received daratumumab (or isatuximab) anti-CD38 therapy during induction therapy.[130] Patients were randomly assigned to receive either Dara-R or lenalidomide alone.

The prospective randomized AURIGA trial (NCT03901963) included 200 patients with newly diagnosed multiple myeloma who achieved a very good or better partial response, were MRD-positive on bone marrow (10-5), and who had not received daratumumab (or isatuximab) anti-CD38 therapy during induction therapy.[130] Patients were randomly assigned to receive either Dara-R or lenalidomide alone.

At a median follow-up of 32.3 months, the 30-month PFS rate was 82.7% for patients who received Dara-R and 66.4% for patients who received lenalidomide alone (HR, 0.53; 95% CI, 0.29–0.97; P = .036).[130][Level of evidence B1]

The prospective randomized AURIGA trial (NCT03901963) included 200 patients with newly diagnosed multiple myeloma who achieved a very good or better partial response, were MRD-positive on bone marrow (10-5), and who had not received daratumumab (or isatuximab) anti-CD38 therapy during induction therapy.[130] Patients were randomly assigned to receive either Dara-R or lenalidomide alone.

The MRD-negative (10-6) conversion rate was 23.2% for patients who received Dara-R and 5.0% for patients who received lenalidomide alone (OR, 5.97; 95% CI, 2.15–16.58; P = .0002).

The prospective randomized AURIGA trial (NCT03901963) included 200 patients with newly diagnosed multiple myeloma who achieved a very good or better partial response, were MRD-positive on bone marrow (10-5), and who had not received daratumumab (or isatuximab) anti-CD38 therapy during induction therapy.[130] Patients were randomly assigned to receive either Dara-R or lenalidomide alone.

Grade 3 or 4 cytopenias occurred in 54.2% of patients who received Dara-R versus 46.9% of patients who received lenalidomide alone. Infections occurred in 18.8% of patients who received Dara-R versus 13.3% of patients who received lenalidomide alone.

A prospective randomized trial of 460 patients with newly diagnosed multiple myeloma who had completed induction therapy and autologous SCT compared lenalidomide maintenance with placebo.[131]

A prospective randomized trial of 460 patients with newly diagnosed multiple myeloma who had completed induction therapy and autologous SCT compared lenalidomide maintenance with placebo.[131]

With a median follow-up of 91 months, the median OS for the lenalidomide maintenance group was 113.8 months (95% CI, 100.4−not reached) versus 84.1 months for the placebo group (range, 73.8−106.0 months; HR, 0.61; 95% CI, 0.46−0.80; P = .0004).[131][Level of evidence A1]

A prospective randomized trial of 460 patients with newly diagnosed multiple myeloma who had completed induction therapy and autologous SCT compared lenalidomide maintenance with placebo.[131]

This translated to a 5-year OS rate of 76% (95% CI, 70%−81%) for the lenalidomide group versus 64% (95% CI, 58%−70%) for the placebo group.

A prospective randomized trial evaluated lenalidomide maintenance in 1,917 patients newly diagnosed with or without transplant.[132]

A prospective randomized trial evaluated lenalidomide maintenance in 1,917 patients newly diagnosed with or without transplant.[132]

With a median follow-up of 31 months, lenalidomide showed improved median PFS, 39 months (95% CI, 36−42) versus 20 months (range, 18−22) (HR, 0.46; 95% CI, 0.41−0.53; P < .0001), but lenalidomide failed to significantly improve the 3-year OS rate, 78.6% (95% CI, 75.6%−81.6%) versus 75.8% (72.4%−79.2%) (HR, 0.87; 95% CI, 0.73−1.05; P = .15).[132][Level of evidence B1]

A meta-analysis included 1,208 patients with newly diagnosed disease who underwent an autologous SCT.[133]

A meta-analysis included 1,208 patients with newly diagnosed disease who underwent an autologous SCT.[133]

With a median follow-up of 79.5 months, OS was not reached for the lenalidomide maintenance group versus 86 months for the placebo or observation group (HR, 0.75; 95% CI, 0.63‒0.90; P = .001).[133][Level of evidence A2]

A meta-analysis of 7,730 patients in randomized clinical trials investigated lenalidomide or thalidomide maintenance in patients with newly diagnosed myeloma, with or without transplant.[134]

A meta-analysis of 7,730 patients in randomized clinical trials investigated lenalidomide or thalidomide maintenance in patients with newly diagnosed myeloma, with or without transplant.[134]

The immunomodulatory maintenance therapy significantly improved PFS (HR, 0.62; 95% CI, 0.57−0.67; P < .001), but failed to significantly improve OS (HR, 0.93; 95% CI, 0.85−1.01; P = .082).[134][Level of evidence B1]

A meta-analysis of 5,073 patients in randomized clinical trials investigated maintenance therapy in patients with newly diagnosed myeloma.[135]

A meta-analysis of 5,073 patients in randomized clinical trials investigated maintenance therapy in patients with newly diagnosed myeloma.[135]

Lenalidomide (with or without prednisone) significantly improved PFS (HR, 0.47; 95% CI, 0.39−0.55), but also failed to significantly improve OS (HR, 0.76; 95% CI, 0.51−1.16).[135][Level of evidence B1]

A prospective randomized trial of lenalidomide maintenance versus no maintenance after induction with melphalan and prednisone or melphalan, prednisone, and lenalidomide included patients aged 65 years and older who were not eligible for transplant.[27]

A prospective randomized trial of lenalidomide maintenance versus no maintenance after induction with melphalan and prednisone or melphalan, prednisone, and lenalidomide included patients aged 65 years and older who were not eligible for transplant.[27]

The results showed a 66% reduction in the rate of progression (HR, 0.34; P < .001), which translated to an EFS of 31 months versus 14 months in favor of maintenance lenalidomide.[27][Level of evidence B1]

A prospective randomized trial (CASSIOPEIA [NCT02541383]) evaluated daratumumab maintenance versus no maintenance for patients with newly diagnosed myeloma. Patients had already received bortezomib, thalidomide, and dexamethasone with or without daratumumab as induction before autologous SCT.[136]

A prospective randomized trial (CASSIOPEIA [NCT02541383]) evaluated daratumumab maintenance versus no maintenance for patients with newly diagnosed myeloma. Patients had already received bortezomib, thalidomide, and dexamethasone with or without daratumumab as induction before autologous SCT.[136]

With a median follow-up of 35.4 months after maintenance randomization, the median PFS was not reached in the daratumumab arm and was 46.7 months (40.0–not evaluable) with observation only (HR, 0.53; 95% CI, 0.42–0.68; P < .0001).[136][Level of evidence B1]

A prospective randomized trial evaluated ixazomib maintenance versus no maintenance for patients with newly diagnosed myeloma who were not undergoing autologous SCT after induction therapy.[137]

A prospective randomized trial evaluated ixazomib maintenance versus no maintenance for patients with newly diagnosed myeloma who were not undergoing autologous SCT after induction therapy.[137]

With a median follow-up of 41 months, the median PFS favored ixazomib maintenance at 17.4 months versus 9.4 months (HR, 0.66; 95% CI, 0.54–0.80; P < .001).[137][Level of evidence B1]

A prospective trial (NCT02659293) evaluated maintenance therapy in patients with newly diagnosed melanoma who had received induction therapy and autologous SCT. Patients were randomly assigned to receive maintenance therapy with either 3 years of carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone.[138]

A prospective trial (NCT02659293) evaluated maintenance therapy in patients with newly diagnosed melanoma who had received induction therapy and autologous SCT. Patients were randomly assigned to receive maintenance therapy with either 3 years of carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone.[138]

With a median follow-up of 33.8 months, the median PFS was 59.1 months for patients who received the triplet maintenance therapy and 41.4 months for patients who received lenalidomide alone (HR, 0.51; 95% CI, 0.31–0.86; P = .012).[138][Level of evidence B1]

A prospective trial (NCT02659293) evaluated maintenance therapy in patients with newly diagnosed melanoma who had received induction therapy and autologous SCT. Patients were randomly assigned to receive maintenance therapy with either 3 years of carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone.[138]

Toxicity and efficacy data are not mature.[138]