Fit patients in good or well-controlled health

A prospective trial included 709 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either D-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[56]

A prospective trial included 709 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either D-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[56]

With a median follow-up of 47.5 months, the 4-year PFS rate was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.30–0.59; P < .001).[56][Level of evidence B1]

A prospective trial included 709 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either D-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[56]

The complete response rate was 87.9% in the D-VRd group and 70.1% in the VRd group (P < .001). The percentage of patients who achieved MRD-negative status favored D-VRd (75.2% vs. 47.5%; P < .001).

A prospective trial included 709 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either D-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[56]

The most common grade 3 or 4 adverse event was neutropenia, which occurred in 62% of patients who received D-VRd and 51% of patients who received VRd.

The phase II GRIFFIN trial (NCT02874742) enrolled 207 patients with newly diagnosed transplant-eligible multiple myeloma. Patients were randomly assigned to receive induction therapy with either D-VRd or VRd. Patients then received an autologous SCT, two more cycles of the induction regimen, and 2 years of maintenance therapy with Dara-R (daratumumab and lenalidomide) or lenalidomide alone depending on the original randomization.[57]

The phase II GRIFFIN trial (NCT02874742) enrolled 207 patients with newly diagnosed transplant-eligible multiple myeloma. Patients were randomly assigned to receive induction therapy with either D-VRd or VRd. Patients then received an autologous SCT, two more cycles of the induction regimen, and 2 years of maintenance therapy with Dara-R (daratumumab and lenalidomide) or lenalidomide alone depending on the original randomization.[57]

With a median follow-up of 49.6 months, the percentage of patients with a stringent complete response was 67% in the D-VRd group and 48% in the VRd group (odds ratio [OR], 2.18; 95% CI, 1.22–3.89; P = .0079).[57][Level of evidence B3]

The phase II GRIFFIN trial (NCT02874742) enrolled 207 patients with newly diagnosed transplant-eligible multiple myeloma. Patients were randomly assigned to receive induction therapy with either D-VRd or VRd. Patients then received an autologous SCT, two more cycles of the induction regimen, and 2 years of maintenance therapy with Dara-R (daratumumab and lenalidomide) or lenalidomide alone depending on the original randomization.[57]

The 4-year PFS rate was 87.2% in the D-VRd group and 70.0% in the VRd group (HR, 0.45; 95% CI, 0.21–0.95; P = .032).[57][Level of evidence B3]

The phase II GRIFFIN trial (NCT02874742) enrolled 207 patients with newly diagnosed transplant-eligible multiple myeloma. Patients were randomly assigned to receive induction therapy with either D-VRd or VRd. Patients then received an autologous SCT, two more cycles of the induction regimen, and 2 years of maintenance therapy with Dara-R (daratumumab and lenalidomide) or lenalidomide alone depending on the original randomization.[57]

The median OS was not reached in either group (HR, 0.90; 95% CI, 0.31–2.56; P = .84).

The phase II GRIFFIN trial (NCT02874742) enrolled 207 patients with newly diagnosed transplant-eligible multiple myeloma. Patients were randomly assigned to receive induction therapy with either D-VRd or VRd. Patients then received an autologous SCT, two more cycles of the induction regimen, and 2 years of maintenance therapy with Dara-R (daratumumab and lenalidomide) or lenalidomide alone depending on the original randomization.[57]

A Markov model using MRD status to predict PFS suggested improved quality of life and lower cost over 10 years with the use of daratumumab in the first-line setting.[58]

A prospective trial, reported in abstract form, included 662 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either I-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[13]

A prospective trial, reported in abstract form, included 662 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either I-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[13]

With a median follow-up of 47.0 months, the 3-year PFS rate was 83% in the I-VRd group and 75% in the VRd group (HR, 0.70; 95% CI, 0.52–0.94; P = .02).[13][Level of evidence B1]

A prospective trial, reported in abstract form, included 662 transplant-eligible patients with newly diagnosed myeloma. Patients were randomly assigned to receive either I-VRd or VRd. All patients received an autologous SCT and subsequent lenalidomide maintenance therapy.[13]

Isatuximab is given intravenously (IV), unlike daratumumab, which is given subcutaneously.

In the multicenter phase II OPTIMUM trial (NCT03188172), 412 newly diagnosed patients were screened to identify 103 patients with ultra–high-risk (UHR) myeloma or plasma cell leukemia.[59] UHR myeloma was defined by the presence of at least two specified genetic risk markers (t(4;14), t(14;16), t(14;20), del (1p), 1q gain, and del 17p)) and/or SKY92 gene expression risk signature. All patients were treated with D-CVRd induction for six cycles (or until maximum response), autologous SCT consolidation, and D-VRd consolidation followed by Dara-R maintenance.[60]

In the multicenter phase II OPTIMUM trial (NCT03188172), 412 newly diagnosed patients were screened to identify 103 patients with ultra–high-risk (UHR) myeloma or plasma cell leukemia.[59] UHR myeloma was defined by the presence of at least two specified genetic risk markers (t(4;14), t(14;16), t(14;20), del (1p), 1q gain, and del 17p)) and/or SKY92 gene expression risk signature. All patients were treated with D-CVRd induction for six cycles (or until maximum response), autologous SCT consolidation, and D-VRd consolidation followed by Dara-R maintenance.[60]

With a median follow-up of 41.2 months, the 30-month PFS rate was 77% (95% CI, 69%–81%) for patients who received the study treatment versus 40% (95% CI, 31%–49%) for an historical control group who received KCRD (carfilzomib, cyclophosphamide, lenalidomide, and dexamethasone).[59][Level of evidence C2] The 30-month OS rate was 84% (95% CI, 76%–91%) for patients who received the OPTIMUM regimen and 74% (95% CI, 66%–82%) for the historical control KCRD regimen.[59][Level of evidence C1]

In the multicenter phase II OPTIMUM trial (NCT03188172), 412 newly diagnosed patients were screened to identify 103 patients with ultra–high-risk (UHR) myeloma or plasma cell leukemia.[59] UHR myeloma was defined by the presence of at least two specified genetic risk markers (t(4;14), t(14;16), t(14;20), del (1p), 1q gain, and del 17p)) and/or SKY92 gene expression risk signature. All patients were treated with D-CVRd induction for six cycles (or until maximum response), autologous SCT consolidation, and D-VRd consolidation followed by Dara-R maintenance.[60]

The study design did not prove that D-CVRd is the preferred regimen for patients with UHR myeloma, but it is a feasible regimen for further randomized trials in this patient population.