E-PROOF: E-intervention for protein intake and resistance training to optimize function: A study protocol.

BACKGROUND: Accounting for more than 60% of cancer survivors, older (≥65 years) cancer survivors have a 2- to 5-fold risk of physical function impairment, compared to cancer-free peers. One strategy to improve physical function is dietary and resistance training interventions, which improve muscle strength and mass by stimulating muscle protein synthesis. The E-PROOF (E-intervention for Protein Intake and Resistance Training to Optimize Function) study will examine the feasibility, acceptability, and preliminary efficacy of a 12-week randomized controlled trial of an online, tailored nutritional and resistance training education and counseling intervention to improve physical function and associated health outcomes (muscle strength, health-related quality of life (HRQoL), self-efficacy, and weight management). METHODS: In this study, 70 older cancer survivors will be randomized to one of two groups: experimental (receiving remote behavioral counseling and evidence-based education and resources), and control (general survivorship education). We will examine the intervention effects on physical function, muscle strength, HRQoL, self-efficacy, weight, and waist circumference during a 12-week period between the experimental and control groups. Three months following the end of the intervention, we will conduct a follow-up assessment to measure physical function, muscle strength, and HRQoL. SIGNIFICANCE AND IMPACT: This study is the first synchronous, online protein-focused diet and resistance training intervention among older cancer survivors. This novel study advances science by promoting independent health behaviors among older cancer survivors to improve health outcomes, and provide foundational knowledge to further address this growing problem on a wider scale through online platforms.

Determining the relationship of p16INK4a and additional molecular markers of aging with clinical frailty in hematologic malignancy.

PURPOSE: Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I2) in patients with HM. METHODS: 70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16INK4a expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I2) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I2. RESULTS: Age-adjusted p16INK4a was similar in newly diagnosed patients and healthy controls (p > 0.1). PBTL p16INK4a levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09-0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11-0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I2 model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16INK4a [AUC = 0.76, 95% CI (0.56-0.98); p = 0.01], Hannum [AUC = 0.70, 95% CI (0.54-0.85); p = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55-0.86); p = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57-0.88); p = < 0.01] measures showed the greatest potential to identify clinical frailty using the I2. CONCLUSIONS: Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM. IMPLICATIONS FOR CANCER SURVIVORS: We developed the I2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.

Psychoneuroimmunology in multiple myeloma and autologous hematopoietic stem cell transplant: Opportunities for research among patients and caregivers.

Multiple myeloma (MM) is an incurable cancer and is the leading indication for autologous hematopoietic stem cell transplantation (HSCT). To be eligible for HSCT, a patient must have a caregiver, as caregivers play a central role in HSCT preparation and recovery. MM patients remain on treatment indefinitely, and thus patients and their caregivers face long-term challenges including the intensity of HSCT and perpetual therapy after transplant. Importantly, both patients and their caregivers show heightened depressive and anxiety symptoms, with dyadic correspondence evidenced and caregivers' distress often exceeding that of patients. An extensive psychoneuroimmunology (PNI) literature links distress with health via immune and neuroendocrine dysregulation as well as biological aging. However, data on PNI in the context of multiple myeloma - in patients or caregivers - are remarkably limited. Distress in MM patients has been associated with poorer outcomes including higher inflammation, greater one year post-HSCT hospital readmissions, and worse overall survival. Further, anxiety and depression are linked to biological aging and may contribute to the poor long-term health of both patients and caregivers. Because MM generally affects older adults, individual differences in biological aging may represent an important modifier of MM biology and HSCT treatment outcomes. There are a number of clinical scenarios in which biologically younger people could be prescribed more intensive therapies, with potential for greater benefit, by using a personalized cancer therapy approach based on the quantification of physiologic reserve. Further, despite considerable psychological demands, the effects of distress on health among MM caregivers is largely unexamined. Within this context, the current critical review highlights gaps in knowledge at the intersection of HSCT, inflammation, and biological aging in the context of MM. Research in this area hold promise for opportunities for novel and impactful psychoneuroimmunology (PNI) research to enhance health outcomes, quality of life, and longevity among both MM patients and their caregivers.

Cellular therapies in older adults with hematological malignancies: A case-based, state-of-the-art review.

Cellular therapies, including autologous stem cell transplant (ASCT), allogeneic hematopoietic cell transplantation (alloHCT), and chimeric antigen receptor- (CAR-) T cell therapies are essential treatment modalities for many hematological malignancies. Although their use in older adults has substantially increased within the past decades, cellular therapies represent intensive treatment approaches that exclude a large percentage of older adults due to comorbidities and frailty. Under- and overtreatment in older adults with hematologic malignancy is a challenge and many treatment decisions are influenced by chronologic age. The advent of efficient and well-tolerated newer treatment approaches for multiple myeloma has challenged the role of ASCT. In the modern era, there are no randomized clinical trials of transplant versus non-transplant strategies for patients ≥65 years. Nonetheless, ASCT is feasible for selected older patients and does not result in long-term compromise in quality of life. AlloHCT is the only curative approach for acute myeloid leukemia of intermediate and unfavourable risk but carries a significant risk for non-relapse mortality depending on comorbidities, general fitness, and transplant-specific characteristics, such as intensity of conditioning and donor choice. However, alloHCT is feasible in appropriately-selected older adults. Early referral for evaluation is strongly encouraged as this is the most obvious barrier. CAR-T cell therapies have shown unprecedented clinical efficacy and durability in relapsed and refractory diffuse large B cell lymphoma. Its use is well tolerated in older adults, although evidence comes from limited case numbers. Whether patients who are deemed unfit for ASCT qualify for CAR-T cell therapy remains elusive, but the tolerability and efficacy of CAR-T cell therapy appears promising, especially for older patients. The evidence from randomized trials is strong in favor of using a comprehensive geriatric assessment (CGA) to reduce treatment-related toxicities and guide treatment intensity in the care for solid tumors; its use for evaluation of cellular therapies is less evidence-based. However, CGA can provide useful information on patients' fitness, resilient mechanisms, and reveal potential optimization strategies for compensating for vulnerabilities. In this narrative review, we will discuss key questions on cellular therapies in older adults based on illustrative patient cases.

Associations of frailty with symptoms, and HRQOL in older cancer survivors after cancer treatments: a systematic review and meta-analyses.

PURPOSE: Frailty in older adult cancer survivors after cancer treatments is associated with various health outcomes. However, there is less agreement on how frailty affects symptoms and health-related quality of life (HRQOL). This systematic review and meta-analysis aimed to evaluate the current literature on frailty, symptoms, and HRQOL, as well as the associations of frailty with these factors in older adult cancer survivors with chemotherapy. METHODS: A review was conducted on peer-reviewed publications from 2008 to 2023, using seven electronic databases. Meta-analyses were performed using random effects models to determine pooled effect estimates for frailty prevalence, symptom severity, and HRQOL scores. RESULTS: A total of 26 studies involving older cancer survivors were included in the analysis. Most of these studies were conducted in Western countries and focused on White survivors, particularly those with breast cancer. The mean pooled prevalence of frailty was 43.5%. Among frail survivors, the most common symptoms reported after cancer treatments were pain (36.4%), neuropathy (34.1%), and fatigue (21.3%). Frailty was associated with higher pooled mean symptom severity (B = 1.23, p = 0.046) and lower functional HRQOL (B = - 0.31, p = 0.051, with marginal significance) after cancer treatments. CONCLUSION: Frail older cancer survivors are at high risk of adverse symptoms and poor HRQOL after cancer treatment. Further research on screening for frailty is needed to prevent older adults from developing worse symptoms burden and maintain HRQOL. It is also essential to understand the mechanisms of the associations between frailty, symptoms and HRQOL in this population.

Understanding the health effects of caregiving stress: New directions in molecular aging.

Dementia caregiving has been linked to multiple health risks, including infectious illness, depression, anxiety, immune dysregulation, weakened vaccine responses, slow wound healing, hypertension, cardiovascular disease, metabolic syndrome, diabetes, frailty, cognitive decline, and reduced structural and functional integrity of the brain. The sustained overproduction of proinflammatory cytokines is a key pathway behind many of these risks. However, contrasting findings suggest that some forms of caregiving may have beneficial effects, such as maintaining caregivers' health and providing a sense of meaning and purpose which, in turn, may contribute to lower rates of functional decline and mortality. The current review synthesizes these disparate literatures, identifies methodological sources of discrepancy, and integrates caregiver research with work on aging biomarkers to propose a research agenda that traces the mechanistic pathways of caregivers' health trajectories with a focus on the unique stressors facing spousal caregivers as compared to other informal caregivers. Combined with a focus on psychosocial moderators and mechanisms, studies using state-of-the-art molecular aging biomarkers such as telomere length, p16INK4a, and epigenetic age could help to reconcile mixed literature on caregiving's sequelae by determining whether and under what conditions caregiving-related experiences contribute to faster aging, in part through inflammatory biology. The biomarkers predict morbidity and mortality, and each contributes non-redundant information about age-related molecular changes -together painting a more complete picture of biological aging. Indeed, assessing changes in these biopsychosocial mechanisms over time would help to clarify the dynamic relationships between caregiving experiences, psychological states, immune function, and aging.

Impact of interval progression before autologous stem cell transplant in patients with multiple myeloma.

In transplant-eligible patients who undergo upfront autologous stem cell transplant (ASCT) for multiple myeloma (MM), standard practice is to treat with six to eight cycles of induction therapy followed by high-dose chemotherapy with ASCT. A gap between the end of induction and the day of ASCT exists to allow stem cell mobilization and collection. Despite attempts to limit the length of this interval, we noticed that some patients experience interval progression (IP) of disease between the end of induction therapy and the day of ASCT. We analyzed 408 MM patients who underwent ASCT between 2011 and 2016. The median length of the interval between end of induction and ASCT was 38 days. We observed that 26% of patients in the entire cohort and 23.6% of patients who received induction with bortezomib-lenalidomide-dexamethasone (VRD) experienced IP. These patients deepened their responses with ASCT, independently of induction regimen. In the entire cohort, IP was significantly associated with shorter PFS in the univariable analysis (Hazard Ratio, HR = 1.37, P = 0.022) but not in the multivariable analysis (HR = 1.14, P = 0.44). However, analyzing only patients who received VRD as induction, progression-free survival (PFS) remained inferior in both the univariable (HR = 2.02; P = 0.002) and the multivariable analyses (HR = 1.96; P = 0.01). T cells and natural killer (NK) cells are increasingly studied targets of immunomodulatory therapy, as immune dysfunction is known to occur in patients with MM. Peripheral blood from 35 MM patients were analyzed. At time of ASCT, patients with IP had significantly increased percentages of CD3+CD8+CD57+ CD28- (P = 0.05) and CD3+CD4+LAG3+ (P = 0.0022) T-cells, as well as less CD56bright and CD56dim NK cells bearing activated markers such as CD69, NKG2D, and CD226. These data suggest that IP can impact the length of response to ASCT; therefore, further studies on the management of these patients are needed.

Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update.

PURPOSE: To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. METHODS: An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022. RESULTS: A total of 26 publications met eligibility criteria and form the evidentiary basis for the update. RECOMMENDATIONS: The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

Geriatric assessment measures are predictive of outcomes in chronic lymphocytic leukemia.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) commonly affects older adults. However, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in this population. Here, we aim to evaluate the use of a comprehensive geriatric assessment in older (>65 years) untreated patients with CLL to predict outcomes. MATERIALS AND METHODS: We conducted a planned analysis of 369 patients with CLL age 65 or older treated in a phase 3 randomized trial of bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone (A041202). Patients underwent evaluations of geriatric domains including functional status, psychological status, social activity, cognition, social support, and nutritional status. We examined associations among baseline geriatric domains with grade 3+ adverse events using multivariable logistic regression and overall survival (OS) and progression-free survival (PFS) using multivariable Cox regression models. RESULTS: In this study, the median age was 71 years (range: 65-87). In the combined multivariable model, the following geriatric domains were significantly associated with PFS: Medical Outcomes Study (MOS) - social activities survey score (hazard ratio [HR] [95% confidence interval (CI)] 0.974(0.961, 0.988), p = 0.0002) and nutritional status (≥5% weight loss in the preceding six months: (HR [95% CI] 2.717[1.696, 4.354], p < 0.001). MOS - social activities score [HR (95% CI) 0.978(0.958, 0.999), p = 0.038] was associated with OS. No geriatric domains were significantly associated with toxicity. There were no statistically significant interactions between geriatric domains and treatment. DISCUSSION: Geriatric domains of social activity and nutritional status were associated with OS and/or PFS in older adults with CLL. These findings highlight the importance of assessing geriatric domains to identify high-risk patients with CLL who may benefit from additional support during treatment.

Survival outcomes following autologous stem cell transplant with melphalan 140mg/m2 versus 200mg/m2 preparative regimens in patients with multiple myeloma.

The standard preparative regimen for autologous stem cell transplant (ASCT) in multiple myeloma (MM) is 200 mg/m2 of intravenous melphalan; however, a dose of 140 mg/m2 is often used when concerns exist related to patient age, performance status, organ function, and other factors. It is unclear whether a lower dose of melphalan impacts post-transplant survival outcomes. We performed a retrospective review of 930 patients with MM who underwent ASCT with 200 mg/m2 versus 140 mg/m2 melphalan. On univariable analysis, no difference in progression-free survival (PFS) was observed, however, an overall survival (OS) benefit was observed in patients receiving 200 mg/m2 melphalan (p = 0.04). Multivariable analyses showed patients receiving 140 mg/m2 faired no worse than those receiving 200 mg/m2. While a subset of younger patients with normal renal function may achieve superior OS with a standard dose of 200 mg/m2 melphalan, these findings suggest an opportunity to individualize the ASCT preparative regimen to optimize outcomes.

The Transplantation Ecosystem: A New Concept to Improve Access and Outcomes for Older Allogeneic Hematopoietic Cell Transplantation Patients.

Allogeneic hematopoietic cell transplantation (HCT) is increasingly offered to older adults with hematologic malignancies, even though nonrelapse mortality remains a major concern in older patients owing to more comorbidities and greater frailty compared with their younger counterparts. The importance of patient fitness, a well-matched donor, and disease control to the success of allogeneic HCT have been well documented; however, these factors fail to account for the impact of the complex transplantation ecosystem (TE) that older adult HCT candidates must navigate. We propose a definition of the TE modeled after the social determinants of health. Furthermore, we outline a research agenda aimed at increasing understanding of the roles of individual social determinants of transplantation health in the larger ecosystem and how they may benefit or harm older adult HCT candidates. Herein we define the TE and its individual tenets, the social determinants of transplantation health. We review the available literature while incorporating the expertise of the membership of the American Society for Transplantation and Cellular Therapy (ASTCT) Special Interest Group for Aging. The membership of the ASTCT Special Interest Group for Aging identify knowledge gaps and strategies to address them for each of the described social determinants of transplantation health. The ecosystem is an essential but underappreciated pillar for transplant access and success. We put forth this novel research agenda seeking to gain a better understanding of the complexity of HCT in older adults and develop strategies to improve access to HCT, survival, and quality of life.

Risk Factors for Immune Checkpoint Inhibitor Immunotherapy Toxicity Among Older Adults with Cancer.

OBJECTIVES: Immune checkpoint inhibitor immunotherapy (IO) is revolutionizing cancer care but can lead to significant toxicity. This study seeks to describe potential risk factors for immune-related adverse events (irAEs) specifically among older adults. MATERIALS AND METHODS: This was a retrospective study at a single academic comprehensive cancer center based on chart review data abstracted by physicians. For patients aged ≥70 years, frequency, type, and grade of irAEs and their association with baseline patient demographics, comorbidities, mobility, and functional status were characterized using bivariate analysis. Based on those results, multivariable logistic regressions were constructed to model the association between these characteristics with any grade and grade 3 or higher irAEs. RESULTS: Data were analyzed for 238 patients aged ≥70 years who received IO for mostly (≥90%) advanced cancer between 2011 and 2018. Thirty-nine percent of older adults experienced an irAE and 13% experienced one that was grade 3 or higher. In the multivariable analysis, depression was associated with an increased incidence of any grade irAE, while decreased life-space mobility was associated with an increased incidence of grade ≥3 irAEs. CONCLUSION: Most characteristics of special interest among older adults, include fall risk, weight loss, cognitive limitations, and hearing loss, were not associated with irAEs in our study. However, decreased life-space mobility and depression are potential risk factors for IO toxicity among older adults with advanced cancer. Interventions designed to evaluate and mitigate modifiable risk factors for treatment-related toxicity are needed, and the results of this study may be useful for guiding those efforts.

A real-world data analysis of predictors of early mortality after a diagnosis of multiple myeloma.

BACKGROUND: Despite the increased availability and use of novel therapies for multiple myeloma, early mortality is a pervasive challenge with a significant impact on older adults. Reported rates and predictors of early mortality have varied in the literature, with most studies seldom focusing on community-treated patients. METHODS: In this retrospective cohort analysis of a real-world electronic health record-derived deidentified database of 7512 patients newly diagnosed with multiple myeloma between January 1, 2011, and February 2, 2021, and treated primarily in US-based community oncology practices, factors associated with early mortality (defined as death within 6 months after the multiple myeloma diagnosis) were examined with the use of binary logistic regression. RESULTS: The median age was 70 years overall. We found an overall early mortality rate of 8.3%, with 73% of early deaths occurring in those aged ≥70 years. Among the early deaths, only 49 patients (8.7%) had documented disease progression before death (median time to progression, 30 days [interquartile range, 7-53 days]). Baseline factors associated with higher odds of early mortality included an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, Revised International Staging System (R-ISS) stage III, an age ≥ 70 years, receipt of proteasome inhibitor-doublet therapy, a light-chain isotype, and the presence of renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Among those aged ≥70 years, ECOG PS ≥ 2 and R-ISS stage III remained the strongest predictors of early mortality. CONCLUSIONS: Early mortality disproportionately affects older adults (aged ≥70 years) with multiple myeloma. Interventions to support this population are needed to reduce disparate survival outcomes. PLAIN LANGUAGE SUMMARY: Factors associated with an increased risk of dying within 6 months (early mortality) of a new diagnosis of multiple myeloma (MM) among 7512 mostly community-treated patients with MM were evaluated. The early mortality rate was 8.3%; among those deaths, 49 patients (8.7%) had documented evidence of MM progression before death. The risk of early mortality was greatest for older patients (aged ≥70 years) and those with a poor performance status, poor kidney function, a higher disease stage, and light-chain MM and those receiving two-drug MM therapies. These findings highlight the need for supportive interventions geared toward older adults with MM.

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

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.

Comparison of Patient Outcomes With Two Different Formulations of Melphalan as Conditioning Chemotherapy for Autologous Hematopoietic Cell Transplantation in Multiple Myeloma.

BACKGROUND: High-dose melphalan (HDM) with autologous hematopoietic cell transplantation (AHCT) after induction chemotherapy is considered standard of care in transplant-eligible patients with newly-diagnosed multiple myeloma (MM). Alkeran melphalan has propylene glycol as a solvent (PG-mel) while Evomela utilizes a propylene glyclol-free formulation (PGF-mel). We evaluated the differences in efficacy and safety of the 2 formulations as there are no prospective head-to-head trials. METHODS: We retrospectively reviewed the medical records of all 259 consecutive MM patients who received PGF-mel as part of HDM-AHCT at The Ohio State University (OSU). The comparator group was the preceding 255 patients who received PG-mel. RESULTS: Baseline patient characteristics were similar between the 2 groups. Post-AHCT rates of relapse were comparable in the PG-mel and PGF-mel groups. Some adverse events were observed at a higher frequency in the PG-mel group compared to the PGF-mel group (grade ≥ 2 mucositis, febrile neutropenia, other infectious complications, and acute renal insufficiency). Time to neutrophil engraftment was slightly longer in the PG-mel group while time to platelet engraftment was longer in PGF-mel group. Red cell transfusion requirement was higher with the use of PG-mel but not platelet transfusion. Duration of hospitalization was slightly shorter with PGF-mel but readmission rates within 30 days of discharge were higher. CONCLUSION: Considering possible confounding factors could possibly account for observed differences in some adverse events, the comparable treatment responses, and difference in cost of the 2 formulation, The OSU reverted to PG-mel as the preferred formulation for HDM-AHCT in MM.

Outcomes After Salvage Autologous Hematopoietic Cell Transplant for Patients With Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience.

BACKGROUND: The role of salvage autologous hematopoietic cell transplantation (sAHCT2) for patients with relapsed/refractory multiple myeloma (RRMM) in the era of modern therapeutics is unclear. As prospective data is limited, we conducted a retrospective analysis to determine the outcomes of sAHCT2. PATIENTS AND METHODS: We conducted a single-institution, retrospective analysis of patients who received sAHCT2 at The Ohio State University from 2000 to 2018. Patients who received a second transplant as part of a planned tandem or autologous-allogeneic transplant were excluded. RESULTS: Fifty-seven patients were treated with sAHCT2. Patients had a median of 2 lines of therapy after AHCT1 prior to their sAHCT2; 70% had prior immunomodulatory imide drugs, 82% had prior proteasome inhibitor, and 20% had prior anti-CD38 monoclonal antibodies as part of re-induction therapy. Forty-two percent of patients attained ≥VGPR prior to sAHCT2. Seventy-four were treated with melphalan 200 mg/m2 as conditioning regimen before infusion of a median of 3.8 × 106 CD34+ cells/kg. Fifty-eight percent patients had maintenance therapy and 81% patients attained CR/VGPR as the best response after sAHCT2. The median PFS and OS after sAHCT2 were 1.6 and 3.6 years, respectively. On multivariable analysis, high-risk cytogenetics, not having attained CR/VGPR, and having more than 2 lines of therapy post-AHCT1 were associated with inferior PFS. Melphalan 140 mg/m2 compared to melphalan 200 mg/m2 and no maintenance therapy compared to maintenance therapy were not associated with inferior PFS. There was no transplant-related mortality in this patient cohort. CONCLUSIONS: For MM patients deriving durable remission after their AHCT1, sAHCT2 was safe and resulted in deep and durable remissions.

Prognosis of older patients with newly diagnosed AML undergoing antileukemic therapy: A systematic review.

BACKGROUND AND OBJECTIVE: The prognostic value of age and other non-hematological factors in predicting outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) undergoing antileukemic therapy is not well understood. We performed a systematic review to determine the association between these factors and mortality and health-related quality of life or fatigue among these patients. METHODS: We searched Medline and Embase through October 2021 for studies in which researchers quantified the relationship between age, comorbidities, frailty, performance status, or functional status; and mortality and health-related quality of life or fatigue in older patients with AML receiving antileukemic therapy. We assessed the risk of bias of the included studies using the Quality in Prognostic Studies tool, conducted random-effects meta-analyses, and assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We included 90 studies. Meta-analysis showed that age (per 5-year increase, HR 1.16 95% CI 1.11-1.21, high-quality evidence), comorbidities (Hematopoietic Cell Transplantation-specific Comorbidity Index: 3+ VS less than 3, HR 1.60 95% CI 1.31-1.95, high-quality evidence), and performance status (Eastern Cooperative Oncology Group/ World Health Organization (ECOG/WHO): 2+ VS less than 2, HR 1.63 95% CI 1.43-1.86, high-quality evidence; ECOG/WHO: 3+ VS less than 3, HR 2.00 95% CI 1.52-2.63, moderate-quality evidence) were associated with long-term mortality. These studies provided inconsistent and non-informative results on short-term mortality (within 90 days) and quality of life. CONCLUSION: High-quality or moderate-quality evidence support that age, comorbidities, performance status predicts the long-term prognosis of older patients with AML undergoing antileukemic treatment.