Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE

Mateos, María Victoria; Dimopoulos, Meletios A.; Cavo, Michèle; Suzuki, Kenshi; Knop, Stefan; Doyen, Chantal; Lúcio, Paulo; Nagy, Zsolt; Pour, Luděk; Grosicki, Sebastian; Crepaldi, Andre H; Liberati, Anna Marina; Campbell, Philip; Yoon, Sung Soo; Iosava, Genadi; Fujisaki, Tomoaki; Garg, Mamta; Iida, Shinsuke; Bladé, Joan; Ukropec, Jon; Pei, Huiling; Rampelbergh, Rian Van; Kudva, Anupa; Qi, Ming; Miguel, Jesús F. San

doi:10.1016/j.clml.2021.06.005

Cited by 28 publications

(27 citation statements)

References 24 publications

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“…A frailty subgroup analysis using the same frailty scale as our study was conducted on the phase 3 ALCYONE study of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) [ 27 ]. After a 40.1-month median follow-up, the overall survival (OS) and PFS benefit of D-VMP versus VMP was observed in all frailty subgroups.…”

Section: Discussionmentioning

confidence: 99%

Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

et al. 2022

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In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n = 368; Rd, n = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P < 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P = 0.003). Improved rates of complete response or better and minimal residual disease (10–5) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.

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Section: Discussionmentioning

confidence: 99%

Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

et al. 2022

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“…Medical data were reviewed to categorize the comorbidity of a patient by the modified Charlson Comorbidity Index (CCI) (29). A frailty index adopted in studies on a similar population (30)(31)(32) was set up by adding scores assigned to age, ECOG performance status, and CCI as defined in Supplementary Table S1. A score ≥2 defined the frail population.…”

Section: Methodsmentioning

confidence: 99%

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

et al. 2021

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BackgroundCutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.Patients and MethodsWe built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored.ResultsThe median age was 81 years (range, 36–95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient.ConclusionsIn our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

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“…The simplified frailty score was the next most commonly utilized score (17/43, 39.2%). Among the RCTs it was used in 6 NDMM studies (MAIA [ 31 ], ALCYONE [ 32 ], HOVON 126 [ 33 ], FIRST [ 10 ], HOVON-87 [ 34 ], IFM 2017_03 [ 30 ]) and all of the 8 studies RCT in the R/R setting. Among the non-RCT, it is currently being utilized in 3 studies in the R/R setting (IFM2021_03 [ 35 ], IFM 2018_02 [ 36 ] and KMMWP-164 [ 37 ]).…”

Section: Resultsmentioning

confidence: 99%

The prevalence and outcomes of frail older adults in clinical trials in multiple myeloma: A systematic review

et al. 2023

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Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes.

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Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE

Cited by 28 publications

References 24 publications

Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

The prevalence and outcomes of frail older adults in clinical trials in multiple myeloma: A systematic review

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