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The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease-negativity (10-5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06-1.48]), with HRCAs (0.38 [0.14-1.01]), and with gain/amp(1q21) (0.42 [0.14-1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35-1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM. Video Abstract.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Mieloma Múltiple/diagnóstico , Anciano , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificaciónRESUMEN
BACKGROUND: Medical mistrust, rooted in unethical research, is a barrier to cancer-related health care for Black/African American (AA) persons. Understanding trust, mistrust, and health care experiences is crucial, especially in multiple myeloma (MM), which disproportionately burdens Black/AA persons in incidence and survival. STUDY PURPOSE: This study qualitatively examines the experiences of Black/AA and White dyads (patient with MM and adult caregiver) to gain insights into these phenomena. METHODS: From November 2021 to April 2022, we recruited 21 dyads from the UNC Lineberger Comprehensive Cancer Center. Participants completed a sociodemographic survey and a 60-90 min semi-structured interview. We used ATLAS.ti v9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc). RESULTS: We interviewed 21 racially concordant dyads (11 Black/AA, 10 White) with mean patient ages of 70 (Black/AA) and 72 (White) at enrollment. Both Black/AA and White caregivers had a mean enrollment age of 68. The mean duration from MM diagnosis to enrollment for all patients was 5.5 years. Four key themes emerged: (1) knowledge and trust, (2) heightened emotions and discomfort, (3) differing mental constructs of health care experiences, and (4) mitigating mistrust, which varied by self-identified race. Black/AA participants had greater knowledge of historical events like the U.S. Public Health Service Untreated Syphilis Study at Tuskegee and carried the emotional burden longer. They also emphasized self-learning and self-guided research about MM for informed medical decision-making. Both Black/AA and White dyads emphasized the pivotal role of patient-provider relationships and effective communication in fostering trust and addressing concerns. CONCLUSION: Our study offers contextual insights into the enduring challenges of medical mistrust, particularly within the Black/AA community, and its implications for patients and caregivers accessing and receiving MM-related care. Future studies should leverage these insights to guide the development of multilevel interventions addressing medical mistrust within the Black/AA community.
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Negro o Afroamericano , Cuidadores , Mieloma Múltiple , Confianza , Población Blanca , Humanos , Mieloma Múltiple/psicología , Mieloma Múltiple/terapia , Masculino , Femenino , Anciano , Cuidadores/psicología , Negro o Afroamericano/psicología , Persona de Mediana Edad , Población Blanca/psicología , Anciano de 80 o más Años , Investigación CualitativaRESUMEN
PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.
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Neoplasias de la Mama , Supervivientes de Cáncer , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Casos y Controles , Estudios Prospectivos , Calidad de VidaRESUMEN
There is limited knowledge regarding the prevalence of geriatric impairments and frailty among patients with multiple myeloma (MM) in a real-world setting. This study evaluated the distribution of frailty profiles among 116 patients with newly diagnosed or relapsed MM, using four common frailty scales. The proportion of patients classified as frail varied significantly, ranging from 15.5% to 56.9%, due to differences in how frailty was operationalized between each frailty measure. Functional, cognitive, and mobility impairments were common overall and irrespective of performance status. Analyses between frailty and treatment selection (dose reduction and doublet vs. triplet therapy) demonstrated significant differences in non-steroid MM drug dose reductions between frail vs. non-frail patients, as scored by the International Myeloma Working Group (IMWG) Frailty Index and Simplified Frailty Score (p < .05). A standardized approach to frailty assessment that is practical in application, and beneficial in guiding treatment selection and minimizing treatment related toxicity is necessary to provide optimal tailored care.
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Fragilidad , Evaluación Geriátrica , Mieloma Múltiple , Humanos , Mieloma Múltiple/epidemiología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/diagnóstico , Anciano , Masculino , Femenino , Fragilidad/epidemiología , Prevalencia , Estudios Prospectivos , Anciano de 80 o más Años , Persona de Mediana Edad , Anciano Frágil/estadística & datos numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10-5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high-risk disease (≥2 HRCAs). Video Abstract.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Aberraciones Cromosómicas , Adulto , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/uso terapéuticoRESUMEN
Developing prognostic tools specifically for patients themselves represents an important step in empowering patients to engage in shared decision-making. Incorporating patient-reported outcomes may improve the accuracy of these prognostic tools. We conducted a retrospective population-based study of transplant-ineligible (TIE) patients with multiple myeloma (MM) diagnosed between January 2007 and December 2018. A multivariable Cox regression model was developed to predict the risk of death within 1-year period from the index date. We identified 2356 patients with TIE MM. The following factors were associated with an increased risk of death within 1 year: ageâ >â 80 (HR 1.11), history of heart failure (HR 1.52), "CRAB" at diagnosis (HR 1.61), distance to cancer center (HR 1.25), prior radiation (HR 1.48), no proteosome inhibitor/immunomodulatory therapy usage (HR 1.36), recent emergency department (HR 1.55) or hospitalization (HR 2.13), poor performance status (ECOG 3-4 HR 1.76), and increasing number of severe symptoms (HR 1.56). Model discrimination was high with C-statistic of 0.74, and calibration was very good. To our knowledge, this represents one of the first prognostic models developed in MM incorporating patient-reported outcomes. This survival prognostic tool may improve communication regarding prognosis and shared decision-making among older adults with MM and their health care providers.
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Mieloma Múltiple , Medición de Resultados Informados por el Paciente , Humanos , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Masculino , Femenino , Pronóstico , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Persona de Mediana EdadRESUMEN
New publication provides insights into the impact of disability on outcomes in older adults with multiple myeloma.
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Mieloma Múltiple , Humanos , Anciano , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapiaRESUMEN
INTRODUCTION: Many of the newer treatments for adults with newly-diagnosed and relapsed multiple myeloma (MM) are orally administered. Adherence is a challenge, and little is known about strategies to optimize adherence. MATERIALS AND METHODS: Forty-seven patients initiating orally-administered anti-myeloma therapy were enrolled and randomized in a pilot study to receive either standard of care teaching or the Multinational Association of Supportive Care in Cancer Oral agent Teaching Tool (MOATT), a structured teaching tool. Adherence was measured electronically with a Medication Event Monitoring System (MEMS) cap. Optimal adherence was defined as an adherence rate of ≥90% over the six months study duration. Patients completed surveys regarding cancer therapy satisfaction and self-efficacy for medication management at one month and six months following the initiation of treatment in both arms. RESULTS: The mean adherence of patients over six months was 86.9%; 43.9% of the cohort were classified as non-adherent using the 90% threshold of adherence. Mean adherence was similar among standard of care teaching (87.9%) versus the MOATT intervention tool (85.6%) as was cancer therapy satisfaction and self-efficacy for medication management. DISCUSSION: In our pilot, the MOATT tool was not found to be feasible or acceptable. There were no preliminary differences noted between standard of care teaching versus the structured MOATT teaching tool with regards to overall adherence rates, cancer therapy satisfaction, or self-efficacy in medication management. Overall adherence rates were suboptimal in our study. Future research should work to identify aspects of educational interventions which are effective, and investigate different strategies which can be used to supplement patient education and potentially optimize medication adherence in patients with MM.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Proyectos Piloto , Cumplimiento de la Medicación , Encuestas y Cuestionarios , Administración OralRESUMEN
Due in part to racial disparities and underrepresentation in clinical studies, optimal therapies for Black patients with multiple myeloma remain undefined. This final analysis of GRIFFIN by race showed that the addition of daratumumab (D) to lenalidomide/bortezomib/dexamethasone (RVd) provides clinical benefit among both Black and White transplant-eligible newly diagnosed patients compared with RVd alone. However, Black patients were more likely to discontinue ≥1 drug due to treatment-emergent adverse events. In summary, these findings suggest a benefit of D-RVd front-line therapy among Black and White patients and underscore the importance of equitable treatment access for all patients.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Lenalidomida , Mieloma Múltiple , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Lenalidomida/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Bortezomib/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Negro o AfroamericanoRESUMEN
BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.
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Neoplasias de la Mama , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Adyuvante/efectos adversos , Evaluación Geriátrica/métodos , HospitalizaciónRESUMEN
INTRODUCTION: Many older adults with acute myeloid leukemia (AML) do not receive chemotherapy because of physicians' and patients' concern for toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following new treatments. MATERIALS AND METHODS: As a part of a pragmatic single-center trial, 59 older adults ≥60 years with AML completed geriatric assessment and health-related quality of life measures before treatment and at one month and three months after chemotherapy initiation. Changes in scores of various geriatric assessment measures were computed by subtracting the baseline score from the one-month and three-month scores for each patient. Established cut-offs were used to determine a clinically meaningful change (improvement or worsening). This study provides results of descriptive exploratory analyses. RESULTS: Patients experienced significant comorbidity burden and a high prevalence of functional impairments before treatment, with 56% of patients having ≥2 comorbid conditions, 69% having abnormal cognitive function (using Montreal Cognitive Assessment), 69% having impaired objective physical function (using Short Physical Performance Battery), and 64% having a positive depression screen (Patient Health Questionnaire-9). Patients (n = 53) received treatment with predominantly low-intensity chemotherapy; six patients received intensive chemotherapy. Among those who completed some or all of the three-month evaluation (N = 43), from baseline before treatment to three months later, cognitive function improved (38.7%) or remained stable (38.7%), objective physical function improved (51.6%) or remained stable (22.6%), and depression scores improved (9.4%) or remained stable (53.1%). Global health status score and role functioning moderately improved by a score of >16. DISCUSSION: An exploratory analysis of our phase 2 trial demonstrated improvement or stabilization of cognitive and physical function and depression score at three months in a high proportion of older survivors of AML, despite a high prevalence of frailty and significant comorbidity burden at baseline. These results demonstrate success of treatment in improving cognitive and physical function and depression score, and, if confirmed in larger studies, should encourage oncologists to offer chemotherapy to older adults with AML. CLINICAL TRIAL REGISTRATION: The study is registered in the ClinicalTrials.gov ID: NCT03226418.
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Leucemia Mieloide Aguda , Calidad de Vida , Humanos , Anciano , Leucemia Mieloide Aguda/tratamiento farmacológico , Estado de Salud , Comorbilidad , CogniciónAsunto(s)
Mieloma Múltiple , Humanos , Anciano , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapiaRESUMEN
INTRODUCTION: Older adults with cancer have unique fall risk factors related to their disease and treatment such as polypharmacy and neurotoxic treatments. In this secondary analysis, we identified modifiable risk factors associated with future falls among older adults with advanced cancers. MATERIALS AND METHODS: Data were from the COACH study (ClinicalTrials.gov: NCT02107443; PI: Mohile). Patients were age ≥ 70, had stage III/IV solid tumor or lymphoma, ≥1 geriatric assessment impairment, and were receiving palliative intent treatment. Falls were self-reported at baseline (in the past six months), four to six weeks, three months, and six months. We generated inverse probability weights to account for mortality-related loss to follow-up and applied these in generalized linear mixed models to estimate incidence rate ratios. RESULTS: Of 541 patients (mean age: 77, standard deviation [SD]: 5.27), 140 (26%) reported prior falls at baseline, and 467 (86%) had falls data for ≥1 follow-up timepoint. Of those, 103 (22%) reported at least one fall during the follow-up period, and 112 (24%) had incomplete follow-up due to death. In fully adjusted models, prior falls and impaired Timed Up and Go score were associated with higher incidence of falls over 6 months. DISCUSSION: We identified several potentially modifiable fall risk factors in older adults with advanced cancers. Future studies should consider ways to integrate fall risk assessment into ongoing cancer care and intervene to reduce falls in this population.
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Accidentes por Caídas , Neoplasias , Humanos , Anciano , Accidentes por Caídas/prevención & control , Factores de Riesgo , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias/complicaciones , Medición de Riesgo , IncidenciaRESUMEN
INTRODUCTION: Although geriatric assessments (GAs) are recommended for use in older adults with cancer, their integration into oncology practice remain suboptimal. Here, we report our experience integrating web-enabled GA (WeCARE) into oncology practice as an augmented delivery method and provider interface format to overcome implementation barriers. MATERIALS AND METHODS: Older patients (≥60 years) with a gastro-intestinal (GI) malignancy presenting for an initial visit to medical oncology clinic at a single institution between December 7, 2021 and October 10, 2022 were contacted by staff two days in advance of their visits and sent a link to the WeCARE GA, rather than the paper version used previously. Results were directly embedded into the medical record. We describe our initial implementation outcomes and the results of a provider usability survey. RESULTS: Of 266 eligible patients, 221 (83.1%) were successfully contacted by telephone and 200 (75.2%) completed the WeCARE prior to their appointment. More than one phone call was required to make contact for 35.7% of patients, with a mean duration of phone conversation of 2.8 min. Most patients preferred email delivery to text (63% vs 31%); 4.5% were unable to access surveys due to inadequate technology, and 25.7% brought up additional logistical concerns. Among GI oncology providers surveyed, all six found the WeCARE tool and dashboard acceptable, appropriate, and feasible. However, only a third of providers often or always used the dashboard to inform treatment decisions and guide interventions. DISCUSSION: With nearly three-quarters of patients completing the WeCARE prior to their visits with minimal staff support and time required, this method of administration may be a viable format to overcome barriers to GA implementation. Additional work is needed to integrate the results meaningfully into clinical practice.
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Neoplasias , Pacientes Ambulatorios , Humanos , Anciano , Neoplasias/terapia , Oncología Médica , Evaluación Geriátrica , EnvejecimientoRESUMEN
BACKGROUND: Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (D-RVd) in the GRIFFIN study improved the stringent complete response rate by the end of consolidation in transplantation-eligible patients with newly diagnosed multiple myeloma. Here, we report the findings of the predefined final analysis. METHODS: GRIFFIN was an open-label, randomised, active-controlled, phase 2 trial done in 35 research centres in the USA. Patients had newly diagnosed multiple myeloma with measurable disease by M protein or free light chain, were aged 18-70 years, had an ECOG performance score of 0-2, and were eligible for autologous haematopoietic stem-cell transplantation (HSCT). Patients were randomly assigned (1:1) to four D-RVd or RVd induction cycles, autologous HSCT, two D-RVd or RVd consolidation cycles, and lenalidomide with or without daratumumab maintenance therapy for 2 years. Patients received 21-day cycles of oral lenalidomide (25 mg on days 1-14), subcutaneous bortezomib (1·3 mg/m2 on days 1, 4, 8, and 11), oral dexamethasone (40 mg weekly) with or without intravenous daratumumab (16 mg/kg weekly, cycles 1-4; day 1, cycles 5-6). Maintenance therapy (28-day cycles) was oral lenalidomide (10 mg on days 1-21) with or without daratumumab (16 mg/kg intravenously every 4 or 8 weeks, or 1800 mg subcutaneously monthly). Patients could continue lenalidomide maintenance after study treatment completion. The primary endpoint was stringent complete response rate by the end of consolidation in the response-evaluable population, and has already been reported. Here we report updated stringent complete response rates and secondary outcomes including progression-free survival and overall survival. The trial is registered with ClinicalTrials.gov (NCT02874742) and ended on April 8, 2022. FINDINGS: Between Dec 20, 2016, and April 10, 2018, 104 patients were randomly assigned to the D-RVd group and 103 were randomly assigned to the RVd group; most patients were White (85 [82%] in the D-RVd group and 76 [74%] in the RVd group) and male (58 [56%] in the D-RVd group and 60 [58%] in the RVd group). At a median follow-up of 49·6 months (IQR 47·4-52·1), D-RVd improved rates of stringent complete response (67 [67%] of 100] vs 47 [48%] of 98]; odds ratio 2·18 [95% CI 1·22-3·89], p=0·0079), and 4-year progression-free survival was 87·2% (95% CI 77·9-92·8) for D-RVd versus 70·0% (95% CI 55·9-80·3) for RVd, with a hazard ratio (HR) of 0·45 (95% CI 0·21-0·95, p=0·032) for risk of disease progression or death with D-RVd. Median overall survival was not reached for either group (HR 0·90 [95% CI 0·31-2·56], p=0·84). The most common grade 3-4 treatment-emergent adverse events in the D-RVd versus RVd groups were neutropenia (46 [46%] of 99 vs 23 [23%] of 102), lymphopenia (23 [23%] vs 23 [23%]), leukopenia (17 [17%] vs eight [8%]), thrombocytopenia (16 [16%] vs nine [9%]), pneumonia (12 [12%] vs 14 [14%]), and hypophosphataemia (ten [10%] vs 11 [11%]). Serious treatment-emergent adverse events occurred in 46 (46%) of 99 patients in the D-RVd group and in 53 (52%) of 102 patients in the RVd group. One patient in each treatment group reported a treatment-emergent adverse event that resulted in death (bronchopneumonia in the D-RVd group; cause unknown in the RVd group); neither was related to study treatment. No new safety concerns occurred with maintenance therapy. INTERPRETATION: Addition of daratumumab to RVd improved the depth of response and progression-free survival in transplantation-eligible patients with newly diagnosed multiple myeloma. These results justify further evaluation in phase 3 studies. FUNDING: Janssen Oncology.
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Mieloma Múltiple , Trombocitopenia , Humanos , Masculino , Mieloma Múltiple/terapia , Bortezomib/efectos adversos , Lenalidomida/uso terapéutico , Talidomida/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona , Trombocitopenia/etiologíaRESUMEN
Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options. However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations. Currently, two B-cell maturation antigen (BCMA)-directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab) have been approved for late-line (greater than four previous lines) R/R MM in the United States. The purpose of this review is to analyze the recent data for these approved therapies as well as provide an overview of other related CAR T-cell and BsAb therapies under development, including non-BCMA-targeting agents. We review efficacy and safety considerations, with particular focus on cytokine release syndrome, neurotoxicity, and infection risk. The relative merits and limitations of each class of therapy are discussed, as well as the areas of unmet need with respect to optimal sequencing and supportive care measures. We examine the factors that challenge equitable access to these novel therapies across minoritized racial, ethnic, and socioeconomic populations. Although it is evident that CAR T-cell and BsAb therapies will transform treatment paradigms in MM for years to come, significant work remains to identify the optimal utilization of these novel therapies and ensure equitable access.
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Anticuerpos Biespecíficos , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Humanos , Mieloma Múltiple/tratamiento farmacológico , Linfocitos T , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Resultado del Tratamiento , Anticuerpos Biespecíficos/uso terapéuticoRESUMEN
Survival has improved in patients diagnosed with multiple myeloma (MM) over the last two decades; however, there remains a paucity of data on the causes of death in MM patients and whether causes of death change during the disease trajectory. We conducted a retrospective population-based study to evaluate the rates of MM-specific versus non-MM cause of death and to identify factors associated with cause-specific death in MM patients, stratified into autologous stem cell transplant (ASCT) and non-ASCT cohorts. A total of 6,677 patients were included, 2,576 in the ASCT group and 4,010 in the non-ASCT group. Eight hundred and seventy-three (34%) ASCT patients and 2,787 (68%) non-ASCT patients died during the follow-up period. MM was the most frequent causes of death, causing 74% of deaths in the ASCT group and 67% in the non-ASCT group. Other cancers were the second leading causes of death, followed by cardiac and infectious diseases. Multivariable analysis demonstrated that a more recent year of diagnosis and novel agent use within 1 year of diagnosis were associated with a decreased risk of MM-specific death, whereas a history of previous non-MM cancer, older age, and the presence of CRAB criteria at diagnosis increased the risk of non-MM death. Our data suggests that despite improvement in MM outcomes in recent years, MM remains the greatest threat to overall survival for patients. Further advances in the development of effective MM therapeutic agents in both ASCT and non-ASCT populations and patient access to them is needed to improve outcomes.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Trasplante Autólogo , Trasplante de Células MadreRESUMEN
BACKGROUND: Multiple myeloma (MM) is an incurable debilitating blood cancer associated with the lowest health related quality of life (HRQoL) of all cancers. With nearly 88% of adults aged ≥55 years at diagnosis, age-associated physical losses, comorbidities, and social factors contribute to worsening HRQoL. This qualitative study assessed dyadic (patient-informal caregiver) perspectives on the factors contributing to HRQoL in MM survivors. METHODS: We recruited 21 dyads from the UNC-Chapel Hill Lineberger Comprehensive Cancer between 11/2021 and 04/2022. Participants completed a single dyadic semistructured interview capturing broad perspectives on MM. We used ATLAS. ti v 9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk, Inc.). This iterative approach allowed the exploration and identification of themes within and across transcripts. RESULTS: The mean age at enrollment was 71 years (median: 71, range: 57-90) for patients and 68 years (median 67, range: 37-88) for caregivers. All dyads were racially concordant (11 Black/AA and 10 White). However, we aggregated the findings due to no consistent racial differences. Six themes related to (1) physical burden, (2) treatment challenges, (3) losses of independence, (4) caregiver burden, (5) patient and caregiver perseverance, and (6) adjustment to a new normal were identified. Dyads also experienced MM together, resulting in patients and caregivers experiencing changes in their ability to engage in physical and social activities, which further contributed to poor HRQoL. Patients' increased need for social support led to shifts in the caregiver roles, resulting in caregivers feeling burdened by their responsibilities. All dyads acknowledged the need for perseverance and adaptability to a new normal with MM. CONCLUSION: The functional, psychosocial, and HRQoL of older patients with MM and their caregivers remain impacted ≥6 months after a new diagnosis highlighting clinical and research opportunities to focus on preserving or improving the health of dyads living with MM.