Supported via arm's length funding from Bayer

Highlights from

American Society of Hematology

Annual meeting 2018

San Diego 1-4 December 2018

MAIA: Daratumumab with lenalidomide plus dexamethasone for the treatment of transplant-ineligible, newly diagnosed multiple myeloma

Take-home messages
  • Lenalidomide-based therapies, such as lenalidomide plus dexamethasone (Rd), are the current standard of care for patients with transplant-ineligible, newly diagnosed MM
  • The addition of daratumumab to Rd, however, has demonstrated a significant reduction in disease progression or death versus Rd dual therapy in this setting
  • Triple therapy with daratumumab plus Rd was well tolerated, with a safety profile similar to previous trials
“These results strongly support D-Rd as a new standard of care for transplant-ineligible patients with myeloma.”

Dr Thierry Facon, Principle Investigator, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France

The late-breaker session of the American Society of Hematology (ASH) 60th Annual Meeting 2018 included a presentation given by Dr Thierry Facon, Principle Investigator, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France. Dr Facon reported the prespecified interim analysis of the phase III trial MAIA, which showed that the addition of daratumumab to Rd (D-Rd) in patients with transplant-ineligible, newly diagnosed multiple myeloma (NDMM) reduced the risk of disease progression or death by 44% compared with Rd dual therapy.

Daratumumab is a human IgG-kappa monoclonal antibody that targets CD38 with direct in-tumour and immunomodulatory mechanisms of action. It has been approved as monotherapy or in combination with standard-of-care regimens in relapsed/ refractory multiple myeloma (RRMM) and in transplant-ineligible NDMM when used in combination with bortezomib, melphalan and prednisone.

The POLLUX trial investigated D-Rd in patients with RRMM, which showed an increase in median progression-free survival (PFS) by 27 months versus Rd dual therapy (44.3 months median follow-up). This provided the rationale for Dr Facon’s team to investigate the efficacy of the same combination in transplant-ineligible patients with NDMM.

In total, 737 patients with an Eastern Cooperative Oncology Group (ECOG) score of 0-2 and CrCl ≥30 mL/min were enrolled in the MAIA trial. Patients were randomised in a 1:1 ratio to receive either Rd (lenalidomide 25 mg daily, days 1-21 + dexamethasone 40 mg daily or IV weekly) or D-Rd (daratumumab 16 mg/kg IV weekly; every week in cycles 1-2, every 2 weeks in cycles 3-6 and every 4 weeks thereafter), in addition to the Rd regimen stated above. Patients in both arms of the study were treated until disease progression.

Commenting on patient characteristics, Dr Facon noted, “median age was 73 and, very importantly, we had a very high proportion of patients of the age of 75; 44% of patients were above the age of 75.”

The primary endpoint of PFS was met in the trial, with a median follow-up of 28 months. At 30 months, 71% of patients in the D-Rd arm showed no progression versus 56% of patients in the Rd arm (hazard ratio (HR): 0.56; 95% CI: 0.43-0.73; p<0.0001). “This PFS benefit was observed across the majority of subgroups such as age, [international staging system], renal function and ECOG. Looking at cytogenetics, the benefit was apparently the most important in patients with standard risk,” explained Dr Facon.

Secondary endpoints included overall response rate (ORR), complete response, very good partial response (VGPR) rate, overall survival (OS), minimum residual disease (MRD) negativity and safety. The ORR, VGPR, and MRD negativity rates were significantly higher in the D-Rd arm than in the Rd arm (p<0.0001).

D-Rd induced significantly deeper responses, including over three-fold MRD negativity compared with Rd, which was associated with lower risk of progression or death. At 28 months follow-up, 62 (17%) deaths occurred in the D-Rd arm compared with 76 (21%) deaths in the Rd arm (HR: 0.78; 95% CI: 0.56-1.1).

“The safety profile observed in the MAIA study was very consistent with findings from other studies,” Dr Facon noted. Treatment-related haematological adverse events were seen in slightly more patients in the D-Rd arm versus the Rd arm (any grade neutropenia: 57% in the D-Rd arm vs 42% in the Rd arm). “We found very few grade 3 or 4 non-haematological adverse events in the D-Rd arm as well as in the Rd arm, and no new safety signals were observed using D-Rd in NDMM”, he concluded.

Based on the reduction of progression or death in patients with NDMM, and the deeper responses seen with D-Rd compared with Rd, Dr Facon closed his talk by stating “these results strongly support D-Rd as a new standard of care for transplant-ineligible patients with myeloma.”

Based on Facon T, Kumar S K et al. Randomized study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant (MAIA) (abstract LBA-2). Presented on Tuesday 4 December 2018.

Top image: © Racksuz

Article image: © OGphoto

The content and interpretation of these conference highlights are the views and comments of the speakers/ authors.

Supported by