Search

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.

Supplementary table 1. Selected early phase clinical trials evaluating Reolysin single-agent and combination treatment regimens. Abbreviations: SD = stable disease, PR = partial response, CR = complete response; ER = endoplasmic reticulum.

supplemental legend

Supplementary table 2. Five patients experienced at least grade 2 adverse events. Two of the 5 patients received at least 4 cycles of treatment, and the associated adverse events were noted after cycle 1. All cytopenias resolved prior to the completion of the cycle that adverse event occurred. Abbreviations: DL = dose level, m-protein = monoclonal protein, CXDX = cycle X, day X, NA = not available.

Supplementary figure 1. The top ten worst adverse events include grade 1 - 3 events. Grade 1 events included decreased neutrophil, white blood cell, lymphocyte, and platelet counts, increased aspartate aminotransferase and alkaline phosphatase, and nausea. Grade 2 events included decreased neutrophil, white blood cell, and platelet counts, anemia, and myalgia. Grade 3 events included decreased neutrophil, white blood cell, and platelet counts, and hypophosphatemia.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Background: Indefinite maintenance therapy after autologous stem cell transplant (ASCT) is the current standard of care in multiple myeloma (MM). However, in the real world, patients often discontinue treatment due to various reasons. In this study, we sought to analyze the effect of and reasons for early discontinuation of maintenance therapy on survival outcomes, studying patients who received less than 3 years of maintenance therapy (short-term maintenance group) or more than 3 years (continuous maintenance group). Methods: We retrospectively reviewed 340 patients who underwent ASCT from 2005-2016 and received maintenance therapy for at least six months without progression. The patients started maintenance therapy after 100 days of ASCT. Lenalidomide (89%) and bortezomib (10%) were the most commonly used agents for maintenance therapy. The primary endpoints included were progression-free survival (PFS) and overall survival (OS). All the endpoints were measured from the time of ASCT. The discontinuation was defined as permanently stopping the maintenance therapy. Patient, disease, and transplant-related characteristics were compared between the two groups using the Mann-Whitney U test for continuous variables, and chi-squared or Fisher's exact test for categorical variables. The probabilities of PFS and OS were calculated using the Kaplan-Meier (KM) method and compared using log-rank test. Results: One hundred and two (n= 102; 30%) patients discontinued maintenance therapy in the first 3 years (short-term maintenance group), while 238 patients remained on maintenance therapy for ≥ 3 years (continuous maintenance group). The groups had similar baseline characteristics in terms of age, gender, ISS staging, cytogenetics, response before ASCT, and melphalan dosing. About 20% of patients in both groups were older than 65 years. Among those alive at the last contact, the median follow up were 5.4 years and 6.1 years for the short-term and continuous maintenance therapy group, respectively. At the time of the last follow-up, 131/238 (55%) patients in the continuous maintenance group were still on maintenance therapy. The median PFS in the short-term maintenance group was 5.1 years (95% CI: 4.4-7.4) and median OS was 9.8 years (95% CI: 8.2- to NR), whereas in the continuous maintenance group both median PFS (95% CI: 8.5- NR) and OS were not reached. This latter group had significantly longer PFS and OS than the short-term maintenance group with a 5-year estimated PFS of 80% (95%CI: 74-85%) vs. 50% (95% CI: 39-60%) (p The most common reasons for early discontinuation of maintenance therapy (< 3 years) were adverse events related to maintenance therapy (58%). Four patient (4%) patients developed second primary malignancy (SPM) in this group. The most frequent hematological adverse events (AEs) were pancytopenia and isolated neutropenia. Fatigue and diarrhea were the most common non-hematological AEs. The reasons for stopping maintenance in the continued maintenance group were disease progression (24%) and adverse events (14%), while five patients (2%) developed SPM. Conclusion: In our institutional experience, 30 percent of MM patients discontinued maintenance therapy within 3 years of ASCT due to AEs or patient preference. These patients had inferior PFS and OS after ASCT compared to patients on continuous maintenance. Therefore, continuation of maintenance therapy should be strongly encouraged as safely possible and strategies like dose reduction or switching therapy are recommended. Figure 1 Figure 1. Disclosures Bumma: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

As part of ongoing efforts to meaningfully improve recruitment, enrollment, and accrual of older adults into cancer clinical trials, the National Cancer Institute (NCI) sponsored a workshop with experts across the country entitled Engaging Older Adults in the NCI Clinical Trials Network: Challenges and Opportunities. Three working groups, including Study Design, Infrastructure, and Stakeholders, were formed, who worked together to offer synergistic improvements in the system. Here, we summarize the workshop discussions of the Infrastructure Working Group, whose goal was to address infrastructural challenges, identify underlying resources, and offer solutions to facilitate accrual of older adults into cancer clinical trials. Based on preconference work and workshop discussions, four key recommendations to strengthen NCI infrastructure were proposed: 1) further centralize resources and expertise; 2) provide training for clinical research staff; (3) develop common data elements; and 4) evaluate what works and does not work. These recommendations provide a strategy to improve the infrastructure to enroll more older adults in cancer clinical trials.

Older patients with cancer often receive treatment regimens based on their age without considering other objective factors that may influence outcomes. Assessment of frailty can identify older patients who are robust and therefore more likely to benefit from intensive treatment, or conversely, frail and might instead be offered alternative approaches. However, such assessment requires specialised training and dedicated clinical resources. Alternative quantitative biomarkers associated with frailty are lacking. Here, we asked if expression signatures of 74 immune cell, ageing, and senescence-related messenger RNAs in purified peripheral blood T cells could identify associations with clinical frailty in patients with haematological malignancies. We studied 69 patients between the ages of 36 and 92 years (median 76 years) with leukaemia, lymphoma, or multiple myeloma, across two institutions. Expression of four genes (aryl hydrocarbon receptor [AHR], CD27, CD28, and interleukin-2 receptor subunit alpha [IL2RA; CD25]) in T cells was associated with frailty, independent of age. An expression-based regression model had 76% sensitivity and 90% specificity to assign a patient as robust. These data identify measurable peripheral blood correlates of clinical frailty and suggest biomarkers for future prospective assessment.

Background: Older adults with hematologic malignancy (HM) are a growing demographic with heterogenous health needs. Chronologic age, performance status and comorbidities impact the selection and intensity of treatments but may not accurately predict treatment toxicity or resiliency. Here, we conducted longitudinal measures of clinical frailty and epigenetic age to explore the relationships between physiologic aging and fitness. Methods: Newly diagnosed patients >60 years with HM were enrolled in a prospective longitudinal study with biomarkers procured at baseline (pre-therapy) and end-of-study (EOS). EOS was defined as the earliest of the following events: progression, transplant, or 1-year from baseline. Peripheral blood was collected, CD3+ T-cells isolated, and DNA extracted using a column-based commercial nucleic acid kit. Peripheral blood T lymphocytes samples were also procured from healthy controls using identical methods. PBTL was extracted, bisulfite converted, and methylation was quantified using the Illumina 850K EPIC methylation array at the TruDiagnostic core laboratory. Raw data was processed using the minfi pipeline, followed by normalization, batch correction, and KNN-based imputation using the GMQN and impute R packages. Principal-component (PC) PhenoAge measures were calculated using the processed methylation values. Measured clinical phenotypes of fitness included ECOG, independent activities of daily living, physical health scores, comorbidities, cognition (BOMC) and objective measures of function (SPPB). Results: 94 patients with HM (acute leukemia n=35, lymphoma n=23, CLL = 6, plasma cell n=30) with PBTL and clinical fitness data were evaluated. The median chronologic age was 70.55 years (range 28.71 yrs, IQR = 10.84). mPhenoAge was higher in patients with HM (Median = 49.59 yrs, Range = 71.245, IQR = 12.52) than healthy donors (Median = 30.46; Range = 75.58, IQR = 32.83). Patients with acute leukemia had the highest mPhenoAge (57.10 yrs, Range = 61.97, IQR = 30.03; p=3e-04). mPhenoage was lower in patients with ECOG 0 vs ECOG 1 (p=0.011). Patients with Acute leukemia also showed a decrease in mPhenoage at EOS (p=0.034), which was not seen in other HMs. Patient IADLs (p=0.032) and comorbidities (p=0.009) were positively correlated with Epigenetic Age Acceleration (EAA). Patient cognitive score (p=0.053) negatively correlated with EAA. mPhenoAge decreased more in patients who received hypomethylating therapies than those who received high-dose multi-drug chemotherapy, low-dose multi-drug chemotherapy or targeted agents. Conclusions: Physiologic age, as measured by PBTL mPhenoAge, is increased among older adults with HMs relative to healthy controls. PBTL mPhenoAge is highest among HM patients with acute leukemia and changes are associated with clinical phenotypes. PBTL mPhenoAGE decreased with hypomethylating agents in patients with acute leukemia. Citation Format: Ashley E. Rosko, Kaitlyn Dvorak, Jennifer Woyach, Varun Dwaraka, Ryan Smith, Ryann Finlayson, Alice Mims, Christin Burd. Epigenetic age acceleration in older adults with hematologic malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3010.

Background Systemic light chain (AL) amyloidosis is a clonal plasma‐cell neoplasm that carries a poor prognosis. Although AL amyloidosis and Multiple Myeloma (MM) can co‐exist and share various cytogenetic chromosomal abnormalities, little is known about Fluorescent in situ hybridization (FISH) and its prognostic relevance in AL amyloidosis. Aim: The study aims to evaluate the most prevalent FISH cytogenetic abnormalities in AL patients as independent prognostic factors, and assess the impact of cytogenetics on the survival of high‐risk cardiac AL patients. Materials & Methods This retrospective study reviewed 113 consecutive AL patients treated at The Ohio State University (OSU). Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis. Hyperdiploidy was defined as trisomies of at least 2 chromosomal loci. Primary endpoints were progression free survival (PFS) and overall survival (OS). Kaplan Meier curves were used to calculate PFS and OS. The log‐rank test and Cox proportional hazard models were used to test the equality of survival functions and further evaluate the differences between groups. Results FISH abnormalities were detected in 76% of patients. Patients with abnormal FISH trended toward lower overall survival (OS) (p=0.06) and progression free survival (PFS) (p=0.06). The two most prevalent aberrations were translocation t(11;14) (39%) and hyperdiploidy‐overall (38%). Hyperdiploidy‐overall was associated with worsening PFS (p=0.018) and OS (p=0.03), confirmed in multivariable analysis. Patients with del 13q most frequently had cardiac involvement (p=0.006) and was associated with increased bone marrow plasmacytosis (p=0.02). Cardiac AL patients with no FISH abnormalities had much improved OS (p=0.012) and PFS (p=0.018) Conclusions Our findings ultimately reveal the association of hyperdiploidy on survival in AL amyloidosis patients, including the high‐risk cardiac AL population., Hyperdiploidy in AL amyloidosis patients was associated with poor PFS and OS and cardiac AL patients had a strong association with del 13q.

Prophylaxis with fluoroquinolone (FQ) for patients undergoing autologous stem cell transplantation (ASCT) remains controversial. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. In accordance with institutional policy, patients undergoing ASCT for multiple myeloma routinely receive levofloxacin prophylaxis during their period of neutropenia, whereas patients undergoing the ASCT for lymphoma do not. We retrospectively examined patients with multiple myeloma (MM) or lymphoma undergoing ASCT between July 2015 and July 2018 for evidence of positive blood cultures. A total of 172 patients underwent ASCT for lymphoma and 343 underwent ASCT for MM. The 2 cohorts were similar in terms of baseline characteristics. Almost 20% (35 of 172) of the patients with lymphoma and 5.2% (18 of 342) of those with MM had a bloodstream infection (BSI). BSI occurred an average of 2 days earlier in patients with lymphoma compared with patients with MM (day +5 versus day +7; P = .0003). The 2 cohorts recovered absolute neutrophil count at the same time. Hospital length of stay was 2 days shorter for patients with MM (median, 20 days versus 18 days; P = .01). The majority of the organisms were gram-negative in both cohorts. Of the organisms commonly tested for FQ sensitivity, only 1 of 25 was resistant in the lymphoma cohort, compared with 7 of 9 in the MM cohort (P.0001), with 4 being multidrug resistant. The odds of developing a BSI were 4.6 times greater in the lymphoma cohort compared with the MM cohort (95% confidence interval [CI], 2.52 to 8.40; P.0001). In total, 23 of 172 patients with lymphoma (13.4%) and 28 of 342 patients with MM (8.2%) developed Clostridium difficile infection (odds ratio, 1.73; 95% CI, .96 to 3.11; P = .066). Two infection-related deaths occurred in the MM cohort. Our data indicate that FQ prophylaxis reduces the risk of BSI in patients undergoing ASCT but increases the incidence of resistant organisms. We recommend routine antimicrobial prophylaxis in patients undergoing ASCT to reduce the risk of BSI, along with a systematic and regular review of outcomes.

The novel coronavirus (SARS-CoV-2, COVID-19) was first identified in the province of Wuhan, China in December 2019 [1], following the emergence of new cases of pneumonia of unknown etiology. Since then, the manifestations of COVID-19 infections have ranged from asymptomatic to severe respiratory infections, with increased morbidity in older adults including those with co-morbidities and cancer [2,3]. Presently, global mortality is reported at 4.7%, but this varies widely by location, from 0.7% in Germany to 10.8% in Italy [4]. As of April 13, 2020, the number of infections continues to rise well beyond the 1.9 million cases, and approximately 120,000 COVID-19-related deaths that have already occurred globally [5]. Multiple myeloma (MM) is a malignant plasma cell dyscrasia which predominantly affects older and often frail adults. Although tremendous gains have been made for older adults with MM, infections, including respiratory infections, significantly impact the rate of early mortality in these patients [6,7]. Furthermore, older adults with MM have age-associated vulnerabilities leading to heterogeneity in outcomes [8]. The complexity of caring for older patients have increased substantially during this pandemic, due to concern about their risk of severe morbidity of COVID19 infection. Optimal strategies for these patients will involve staging the malignancy/aging, while simultaneously considering the local prevalence of COVID-19 infection. Herein, we discuss strategies for the risk reduction of COVID-19 transmission, treatment stratification of anti-myeloma therapy and discussion regarding goals of care for older adults with MM during the COVID-19 pandemic.

Hematopoietic cell transplant (HCT) is an important aspect of treatment for many hematologic malignancies. As cancer is a disease associated with aging, and hematologic malignancies are no exception, rates of autologous and allogeneic HCT utilization in older adults are on the rise. The most common indications for autologous HCT are multiple myeloma and lymphoma, and for allogenic HCT are acute myeloid leukemia and myelodysplastic syndrome. Older adults into their eighth decade of life can have favorable outcomes after autologous and allogeneic HCT, at least among select patients. Evaluation of older adults prior to HCT can be aided by utilizing a geriatric assessment (GA). GA can identify areas of vulnerability in older adults prior to HCT not captured by more traditional measures. In the future, GA may be utilized to guide interventions prior to HCT to improve outcomes of older adults. Further studies are needed to expand the paucity of data in utilizing GA to identify three groups of patients: those who clearly benefit from HCT, those who would clearly be harmed, and those who might benefit but would require additional support during and after HCT.

Autologous stem cell transplant (ASCT) is the standard of care for patients with multiple myeloma (MM). The clinical significance of peripheral blood T lymphocyte (PBTL) immunologic changes associated with ASCT is poorly understood. Here we evaluated T cell transcriptional messenger RNA profiles and immunophenotypes to correlate immunologic senescence, exhaustion, and anergy with clinical endpoints in a cohort of patients with MM undergoing ASCT. ASCT induced global transcriptional T cell changes and altered molecular levels of markers of T cell subtypes, T cell activation, and exhaustion. These included reduced CD4/CD8 ratio, skewing toward the Th1 subset, reduced expression of costimulatory receptors CD27 and CD28, heightened T cell activation, and increased expression of immune modulatory molecules LAG3 and PD1. Multicolor flow cytometry experiments confirmed altered circulating CD4 and CD8 subsets and skewing toward differentiated effector cells. Moreover, ASCT promoted an exhausted immunophenotype in CD3+CD4+ subsets and a senescent immunophenotype in CD3+CD8+ subsets. Subset-specific altered expression was also seen for surface molecules with immunomodulatory function. ASCT affected soluble levels of molecules with immunomodulatory function by increasing plasma HVEM and TIM3. High molecular LAG3 level was associated with inferior event-free survival post-ASCT (hazard ratio=5.44; confidence interval, 1.92 to 15.46; P = .001; adjusted P [controlling for false discovery rate] = .038). Using a comprehensive evaluation of PBTLs on a molecular and phenotypic level, we have identified that ASCT induces global T cell alterations with CD4 and CD8 subset-specific changes. Moreover, LAG3 emerged as an early biomarker of adverse events post-ASCT. These findings will support the development of treatment strategies targeting immune defects in MM to augment or restore T cell responses.

Post-autologous stem cell transplantation (ASCT) maintenance therapy with lenalidomide is standard of care for patients with multiple myeloma (MM). Effective and tolerable drug combinations may further enhance the clinical response post-ASCT. Vorinostat, a histone deacetylase inhibitor, induces antiproliferative and proapoptotic effects in patients with MM. We hypothesized that combination maintenance therapy would further prolong the clinical response achieved from transplantation. We previously reported that the combination of lenalidomide and vorinostat as maintenance post-ASCT was tolerable in 16 patients with MM. We now present the long-term follow up of these patients. Progression-free survival (PFS) and overall survival (OS) outcomes were characterized using the Kaplan-Meier method. Five patients (31%) had high-risk disease, and the median number of lines of therapy before ASCT was 1 (range, 1 to 5). With a median follow-up of 89.8 months from ASCT, the median PFS was 64.3 months (range, 21.7 months to not reached [NR]), and OS was not reached (median, 53.0 months to NR). At the time of this report, 5 patients remained on the study. The combination of vorinostat and lenalidomide as maintenance post-ASCT is tolerable and induces a durable response. A phase III randomized study of lenalidomide versus a combination with vorinostat is warranted.

Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED with active cancer.Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017.Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics.We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.

Older adults with multiple myeloma (MM) are a growing population, and personalizing treatment based on disease and health status is imperative. Similar to MM staging systems that provide disease-related prognostic information, myeloma-specific frailty tools can better identify subgroups at greatest risk for treatment-related toxicity and early treatment discontinuation, as well as predict overall survival. Several myeloma-specific validated tools are well studied. Although these fitness/frailty scores have shaped our understanding of the heterogeneity among older adults with myeloma, the application of such scores in treatment decision making (ie, transplant considerations, relapse) is an unmet need. Here we outline how to incorporate frailty assessments in the evaluation of older adults with MM in the clinical setting with consideration of other factors such as patient preferences, treatment risks/benefits, life expectancy, and disease biology.

Hematologic malignancies are most likely to present in the seventh and eighth decades of life. Continued population growth will lead to increasing numbers of older adults with hematologic malignancies. Oncology care for older adults is complex and must account for the effect of aging on disease biology and treatment tolerance. Multidisciplinary oncology care has been utilized in solid tumor oncology for decades, initially driven by the need for multi-modality treatment. In this review, we make the case for multidisciplinary oncogeriatric care for older adults with hematologic malignancies in order to best navigate the intersection of aging and blood cancer.

Allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical (haplo) donor has emerged as a suitable alternative in the absence of a matched donor. However, haplo-HCT patients have a higher risk of graft-versus-host disease (GVHD). Hence, bone marrow (BM) stem cell source and post-transplant cyclophosphamide (PTCy) have been routinely used to help mitigate this. Due to ease of collection, peripheral blood (PB) stem cells are increasingly being considered for haplo-HCT. We retrospectively analyzed 74 patients (42 BM and 32 PB) who underwent haplo-HCT at Ohio State University from 2009 to 2018. Median age at transplant was 60 years (yrs) for BM and 54 yrs for PB, (p = 0.45). There was no difference in OS (p = 0.13) and NRM (p = 0.75) as well as PFS (p = 0.10) or GRFS (p = 0.90) between the groups. The BM cohort showed a 3-year OS rate of 63% (95% confidence interval (CI): 46–76), and 3-year PFS of 49% (95% CI: 33–63). For the PB group, 3-year OS and PFS were 78% (95% CI: 59–89) and 68% (95% CI: 49–82), respectively. There were no differences in the incidence of acute GVHD (grade II-IV) (p = 0.31) and chronic GVHD (p = 0.18). Patients receiving BM had a significantly higher risk for relapse with relapse rates by 2 years at 36% (95% CI: 22–50) vs. 16% (95% CI: 6–31) for PB (p = 0.03). The findings from this study suggest that PB is an excellent alternative to BM for haplo-HCT.

High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin’s lymphoma (NHL). However, the optimal conditioning regimen is unclear. Different conditioning regimens prior to AHCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We sought to compare the two regimens for patients with relapsed NHL undergoing AHCT. We retrospectively compared the outcomes of patients treated with BEAM (N = 269) at The Ohio State University and BUCYVP16 (N = 409) at the Cleveland Clinic followed by AHCT between 2006 and 2014. The primary endpoints were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Patient characteristics between the two groups were similar. After a median follow-up of 3.9 years for BEAM and 4.3 years for BUCYVP16 from AHCT, the rate of relapse (p = 0.69), PFS (p = 0.52), and OS (p = 0.11) were similar between the two conditioning regimens. No differences in survival outcomes were seen in disease subtypes. Multivariable analysis showed significant association toward improved OS with BEAM (HR: 1.56, 95% CI 1.16–2.10) (p

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥ 10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥ 11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥ 10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (&gt, 11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

Healthy lifestyles including maintaining a normal weight, consuming a healthy diet, and being physically active can improve prognosis and health-related quality of life (HRQoL) among cancer survivors. The largest proportion of cancer survivors are older adults (≥ 65 years), yet their lifestyle behaviors are understudied. This study sought to examine the lifestyle behaviors (maintaining healthy weight, diet quality, physical activity) of older female cancer survivors and identify associations with HRQoL. Older female cancer survivors (n = 171) completed surveys to assess HRQoL (RAND-36), unintentional weight loss, body mass index (BMI), diet quality (HEI-2015), and physical activity. Demographic information and medical record data were also collected. Descriptive analyses, correlations, and stepwise linear regressions were utilized. Physical and mental HRQoL of the sample (mean age = 74.50 years) were low: 41.94 ± 10.50 and 48.47 ± 7.18, respectively, out of 100. Physical activity was low: 75.3%, 54.2%, and 68.1% reported no strenuous, moderate, and mild physical activity, respectively. Mean BMI was 27.71 ± 6.24 (overweight) with 64% of the participants being overweight or obese. Mean HEI-2015 scores were 66.54 ± 10.0. Engagement in moderate physical activity was associated with higher physical HRQoL (β = 0.42, p = 0.004). Being white (β = 0.53, p

Many hematopoietic cell transplantation (HCT) recipients require rehabilitation due to deconditioning following intensive conditioning regimens and immune reconstitution. HCT recipients are preferentially discharged to home to avoid the risk of exposure to healthcare-associated infection in a rehabilitation facility (RF), with a caregiver who has been provided specific education about the complexity of post-HCT care. This study was conducted to determine the incidence of discharge to an RF following HCT, identify pre-HCT and peri-HCT risk factors for discharge to an RF, and estimate the effect of discharge disposition on overall survival (OS). This retrospective, matched 1:4 case-control study included 56 cases over a 10-year period from a single institution. Controls were matched by transplantation type (autologous versus allogeneic) and date of transplantation. The incidence of discharge to an RF was 2.2%. Controlling for disease, increasing age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04 to 1.15; P.001), female sex (OR, 3.11; 95% CI, 1.32 to 7.32; P = .01), high-risk HCT Comorbidity Index (HCT-CI) score (≥3) (OR, 3.44; 95% CI, 1.39 to 8.52; P = .008), decreasing pre-HCT serum albumin (OR, 2.60; 95% CI, 1.07 to 6.38; P = .037), and development of acute kidney injury during HCT (OR, 4.10; 95% CI, 1.36 to 12.40; P = .012) were associated with discharge to an RF. Discharge to an RF was associated with worse OS and higher nonrelapse mortality (NRM) compared with discharge to home (1-year OS, 70.5% [95% CI, 55.8% to 81.1%] versus 88.8% [95% CI, 83.6% to 92.4%], P.001; 100-day NRM: 9.5% [95% CI, 3.5% to 19.2%] versus 1.8% [95% CI, 0.6% to 4.3%]; P = .03). Discharge to an RF following HCT is a rare event but associated with poor OS. Modifiable risk factors for discharge to an RF, including serum albumin as a measure of nutrition and reversible HCT-CI components, should be prospectively studied to determine the effect of mitigation on discharge disposition and survival.

Multiple myeloma (MM) is an incurable disease with a limited life expectancy of five years from diagnosis. Uncontrolled disease or infections are the main causes of mortality. Daratumumab, a monoclonal antibody against CD38, is approved to treat patients with MM. Its target, CD38, is expressed not only on MM cells but also on common lymphoid precursors and subsets of normal lymphocytes. Daratumumab-induced lymphopenia is common, but its clinical significance is understudied. In this study, we report the baseline characteristics, rates of severe lymphopenia, infections, and clinical trajectory of multiple myeloma patients (n = 100) treated with daratumumab-based regimens at the Ohio State University Comprehensive Cancer Center. We discover high rates of infections, hospital utilization, and severe lymphopenia and identify risks factors for severe lymphopenia, such as low pretreatment absolute lymphocyte count (ALC) values. Severe lymphopenia persists in 23% of patients, resulting in worst survival outcomes. Our data underline the importance of monitoring ALC and consider future use of prophylactic measures or alternative regimens in subsets of MM patients.

Background: Gauging fitness remains a challenge among older adults with hematologic malignancies, and interventions to restore function are lacking. We pilot a structured exercise intervention and novel biologic correlates of aging using epigenetic clocks and markers of immunosenescence to evaluate changes in function and clinical outcomes. Methods: Older adults (n=30) with hematologic malignancy actively receiving treatment were screened and enrolled in a 6-month exercise intervention, the Otago Exercise Programme (OEP). The impact of the OEP on geriatric assessment metrics and health-related quality of life were captured. Clinical outcomes of overall survival and hospital utilization (inpatient length of stay and emergency department use) in relationship to geriatric deficits were analyzed. Results: Older adults (median age, 75.5 years [range, 62–83 years]) actively receiving treatment were enrolled in the OEP. Instrumental activities of daily living and physical health scores (PHS) increased significantly with the OEP intervention (median PHS: visit 1, 55 [range, 0–100]; visit 2, 70 [range, 30–100]; PP=.05). Quality of life (Patient-Reported Outcome Measurement Information System [PROMIS]) improved significantly by the end of the 6-month period (median [range]: visit 1, 32.4 [19.9–47.7]; visit 3, 36.2 [19.9–47.7]; P=.01]. Enhanced measures of gait speed and balance, using the Short Physical Performance Battery scores, were associated with a 20% decrease in risk of death (hazard ratio, 0.80; 95% CI, 0.65–0.97; P=.03) and a shorter hospital length of stay (decrease of 1.29 days; 95% CI, −2.46 to −0.13; P=.03). Peripheral blood immunosenescent markers were analyzed in relationship to clinical frailty and reports of mPhenoAge epigenetic analysis are preliminarily reported. Chronologic age had no relationship to overall survival, length of stay, or emergency department utilization. Conclusions: The OEP was effective in improving quality of life, and geriatric tools predicted survival and hospital utilization among older adults with hematologic malignancies.

Over the last few years, there has been great progress in the treatment of multiple myeloma (MM), with many new agents and combinations having been approved and being now routinely incorporated into treatment strategies for newly diagnosed patients. As a result, patients are experiencing benefits in terms of survival and better tolerance. However, the multitude of treatment options also presents a challenge to select the best options tailored to the specific patient situation. Frontline autologous stem cell transplantation (ASCT) is the standard of care for fit patients younger than age 71 who are newly diagnosed with MM, and triplet combinations are the backbone of induction therapy before ASCT. Post-transplant consolidation and prolonged lower-intensity maintenance are two strategies that have been used to deepen responses and delay progression. For older patients not eligible for ASCT, lenalidomide (len) is increasingly being used as part of frontline therapy, and current approaches are now targeting combinations of anti-CD38 antibodies. Strategies for selecting therapeutic regimens for older adults newly diagnosed with MM can be augmented with use of predictive tools to better capture physiologic age and estimate treatment tolerance. Here we review a decade of trials identifying clinical endpoints and toxicities relevant for the frontline treatment of younger patients and older adults.

Background: Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE’s Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these recommendations are guided by the principle that throughout a patient’s disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.