Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses

Abstract

In the primary analysis (32.3-month median follow-up) of the randomized, phase 3 AURIGA study (NCT03901963), daratumumab-lenalidomide (D-R) maintenance significantly improved MRD-negative conversion rates and reduced the risk of disease progression or death by 47% versus R maintenance in anti-CD38 monoclonal antibody-naïve and post-transplant MRD-positive patients with newly diagnosed MM. Here, we present a post hoc analysis across relevant subgroups, including high-risk cytogenetic abnormalities (HRCAs) per original, revised, and modified International Myeloma Society (IMS) 2024 criteria. MRD-negative (10^-5) conversion rates by 12 months of maintenance were higher for D-R versus R across cytogenetically high-risk subgroups per original (31.8% vs 6.7%), revised (43.8% vs 13.3%), and modified IMS 2024 (41.2% vs 0%) criteria and cytogenetically ultra-high-risk disease (≥2 revised HRCAs; 54.5% vs 0%). Similar trends in overall MRD-negative conversion rates were observed across subgroups. D-R demonstrated a trend towards improved PFS versus R (HR [95% CI]) in cytogenetically high-risk subgroups per original (0.60 [0.21-1.70]), revised (0.53 [0.21-1.31]), and modified IMS 2024 (0.45 [0.13-1.53]) criteria and cytogenetically ultra-high-risk disease (0.61 [0.17-2.25]). Similar outcomes were observed regardless of age or race, with no additional safety concerns among older (≥65 years) or Black patients. These data support the benefit of D-R maintenance regardless of age, race, and risk status.

Fig. 1. Subgroup analysis of MRD-negative (10^–5) conversion rate by 12 months of maintenance.^a

MRD minimal residual disease, D-R daratumumab/lenalidomide, R lenalidomide, CI confidence interval, ITT intent-to-treat, ISS International Staging System, VGPR very good partial response, CR complete response, HRCA high-risk cytogenetic abnormality, NE not estimable, IMS International Myeloma Society. ^aDefined as the proportion of patients who were MRD positive at baseline and achieved MRD-negative status (at 10^–5) by next-generation sequencing by 12 months after maintenance treatment and prior to progressive disease or subsequent antimyeloma therapy. ^bMantel-Haenszel estimate of the common odds ratio for stratified tables was used for the ITT population; Mantel-Haenszel estimate of the common odds ratio for unstratified tables was used for subgroups. An odds ratio >1 indicates an advantage for D-R maintenance. ^cITT population is defined as all patients who were randomized to treatment. ^dResponse status upon entering the study as assessed by International Myeloma Working Group 2016 criteria. ^eHigh-risk cytogenetics per the original definition are defined as ≥1 abnormality including del(17p), t(4;14), and/or t(14;16). ^fRevised high-risk cytogenetics per the revised definition are defined as ≥1 abnormality including del(17p), t(4;14), t(14;16), t(14;20), and/or gain/amp(1q21). ^gNot evaluable because no patient in the R group had MRD-negative conversion. ^hHigh risk per the modified IMS 2024 criteria is defined as the presence of ≥20% del(17p); del(1p32) co-occurring with gain/amp(1q21); or t(4;14), t(14;16), and/or t(14;20) co-occurring with gain/amp(1q21) and/or del(1p32). In the AURIGA study, data were not available on TP53 mutations, beta-2-microglobulin and creatinine levels at the time of multiple myeloma diagnosis, and differentiation between monoallelic versus biallelic del(1p32).

Fig. 2. Subgroup analysis of PFS by cytogenetic risk.

A PFS by cytogenetic risk per original criteria. High-risk cytogenetics per the original definition are defined as ≥1 abnormality including del(17p), t(4;14), and/or t(14;16). B PFS by cytogenetic risk per revised criteria. Revised high-risk cytogenetics per the revised definition are defined as ≥1 abnormality including del(17p), t(4;14), t(14;16), t(14;20), and/or gain/amp(1q21). C PFS by cytogenetic risk per modified IMS 2024 criteria. High risk per the modified IMS 2024 criteria is defined as the presence of ≥20% del(17p); del(1p32) co-occurring with gain/amp(1q21); or t(4;14), t(14;16), and/or t(14;20) co-occurring with gain/amp(1q21) and/or del(1p32). In the AURIGA study, data were not available on TP53 mutations, beta-2-microglobulin and creatinine levels at the time of multiple myeloma diagnosis, and differentiation between monoallelic versus biallelic del(1p32). D PFS by the number of HRCAs, defined as the number of abnormalities from del(17p), t(4;14), t(14;16), t(14;20), and/or gain/amp(1q21). Cytogenetic results at diagnosis (based on clinical report form collected data from local labs) were used in the analysis. PFS, progression-free survival; IMS, International Myeloma Society; HRCA, high-risk cytogenetic abnormality; D-R, daratumumab/lenalidomide; R, lenalidomide; HR, hazard ratio; CI, confidence interval. ^aHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable. An HR <1 indicates an advantage for D-R maintenance.