The relationship of mental health symptoms to chemotherapy toxicity risk in older adults with cancer: Results from the geriatric assessment-driven intervention study.

BACKGROUND: Depression and anxiety are prevalent in older adults with cancer but are often undertreated. Older adults are also at increased risk of chemotherapy toxicity (CT). This study evaluated the impact of depression and anxiety symptoms on severe CT risk in older adults with cancer. METHODS: This is a secondary analysis of a randomized trial (2:1) evaluating geriatric assessment-driven intervention (GAIN) versus standard of care (SOC) to reduce grade 3+ CT in older adults with cancer. Mental health was assessed via the Mental Health Inventory 13. CT was graded by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: A total of 605 patients enrolled (402 GAIN; 203 SOC). Overall, 35% were depressed and 47% were anxious. Patients with depression had increased CT in the SOC arm (70.7% vs. 54.3%; p = .02) but not in the GAIN arm (54.3% vs. 48.5%; p = .27). CT was more likely in SOC patients with depression (odds ratio [OR], 2.03; 95% CI, 1.10-3.72). This association persisted after adjusting for Cancer and Aging Research Group toxicity score (OR, 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85). Depression and CT were not associated in the GAIN arm (OR, 1.26; 95% CI, 0.84-1.91). Anxiety and CT were not associated in either arm. CONCLUSIONS: Elevated depression symptoms are associated with increased risk of severe CT in older adults with cancer, which was mitigated with GAIN. This suggests that treating depression symptoms may lower toxicity risk. Future studies are needed to confirm and investigate the impact of depression-specific interventions on outcomes.

Relapsed or refractory large B-cell lymphoma after chimeric antigen receptor T-cell therapy: Current challenges and therapeutic options.

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR-T therapy have poor outcomes. Multiple mechanisms of CAR-T therapy failure have been proposed but management of these patients remains a challenge. As CAR-T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR-T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody-drug conjugates and next-generation CAR-T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR-T therapy and provide a framework for the ideal sequencing of these novel agents.

Ruxolitinib resistance or intolerance in steroid-refractory acute graft-versus-host disease - a real-world outcomes analysis.

Ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. Ruxolitinib-resistant aGVHD was identified in 48/307 patients. Among patients receiving additional therapy, the overall response rate to next therapy was 36%. Median survival was 21 days. Ruxolitinib intolerance led to treatment discontinuation in 16/307 patients. Ten intolerant patients received additional therapy with 50% experiencing continued improvement of aGVHD. Median survival was 50 days in these patients. These data serve as a baseline for future SR-aGVHD studies.

Quality of life in caregivers of patients receiving chimeric antigen receptor T-cell therapy.

OBJECTIVE: Informal family caregivers provide critical support for patients receiving chimeric antigen receptor (CAR) T-cell therapy. However, caregivers' experiences are largely unstudied. This study examined quality of life (QOL; physical functioning, pain, fatigue, anxiety, and depression), caregiving burden, and treatment-related distress in caregivers in the first 6 months after CAR T-cell therapy, when caregivers were expected to be most involved in providing care. Relationships between patients' clinical course and caregiver outcomes were also explored. METHODS: Caregivers completed measures examining QOL and burden before patients' CAR T-cell therapy and at days 90 and 180. Treatment-related distress was assessed at days 90 and 180. Patients' clinical variables were extracted from medical charts. Change in outcomes was assessed using means and 99% confidence intervals. Association of change in outcomes with patient clinical variables was assessed with backward elimination analysis. RESULTS: A total of 99 caregivers (mean age 59, 73% female) provided data. Regarding QOL, pain was significantly higher than population norms at baseline but improved by day 180 (p < .01). Conversely, anxiety worsened over time (p < .01). Caregiver burden and treatment-related distress did not change over time. Worsening caregiver depression by day 180 was associated with lower patient baseline performance status (p < .01). Worse caregiver treatment-related distress at day 180 was associated with lower performance status, intensive care unit admission, and lack of disease response at day 90 (ps < 0.01). CONCLUSIONS: Some CAR T-cell therapy caregivers experience pain, anxiety, and burden, which may be associated patients' health status. Further research is warranted regarding the experience of CAR T-cell therapy caregivers.

Distress evaluation in a veteran affairs oncology clinic.

Distress in oncology patients (pts) has a negative impact on quality of life, survival, and healthcare satisfaction. Higher distress leads to lower compliance with treatment and follow-up [1-8]. The 2012 American College of Surgeons Commission on Cancer (CoC) standard of care for oncology pts included an assessment for distress [1]. A screening process for distress allows the healthcare team to address these issues early and refer to appropriate resources [2-9]. This project was initiated to meet National Comprehensive Cancer Network (NCCN) and CoC standard of care, identify distress in veterans with cancer, and address these concerns. Patients who attended the Tuesday oncology clinic at the Dayton VAMC were given the NCCN Distress Thermometer (DT) during triage. The treating physician addressed problems identified. The Wilcoxon signed rank test and the Friedman test were used. DTs were completed by 296 pts from March to December 2016. Mean age was 68, 93% male, 83% white, 55% married, and 93% without PTSD. The distress level was not different from T1 through T3. Number of problems decreased over three time periods. Referrals to nutrition, mental health, and social work services increased over time. Although over time periods we found no decrease in distress scores, there was a decline in number of problems. The mean distress score at all but time 4 was < 4, which is considered mild distress. The mean distress score at T4 was 4.36 (n = 14), suggesting that the few pts who return to clinic more than three times may be experiencing more difficult personal and environmental circumstances. Patient sample ranged from those undergoing intensive cancer treatment (e.g., chemotherapy) to less intensive treatment (e.g., hormone injections) to those who completed treatment.

The use of venetoclax-based salvage therapy for post-hematopoietic cell transplantation relapse of acute myeloid leukemia.

For patients with high risk myeloid disease, allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy. Unfortunately, many of these patients relapse after HCT and have a limited survival. The recent approval of venetoclax, an orally bioavailable BCL-2 inhibitor, resulted in significant responses in treatment naïve acute myeloid leukemia (AML), and off-label use in the relapsed/refractory setting is increasing. We report the outcomes of 21 patients who underwent allogeneic HCT for myeloid disease, relapsed with AML, and were treated with venetoclax. Several patients had poor risk features including antecedent hematologic malignancy (6/21), complex karyotype (6/21), and TP53 mutations (5/21). The median age was 64.5 years and time from HCT to relapse was 5.7 months (range: 0.9 to 44.9 months). Of the 19 patients who were assessed for response, there were meaningful treatment responses seen in eight patients: five CR, three CRi, zero PR, for an ORR of 42.1%. Treatment effect was seen in six additional patients, including four in the morphologic leukemia-free state. Nine patients maintained their response for ≥3 months and eight were receiving therapy at data cut. Post-HCT AML relapse has an exceedingly poor outcome, and venetoclax-based therapy is a potent therapy option that should be studied prospectively in this setting.

Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell transplantation in adults with severe aplastic anemia.

The age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included. Outcomes analyzed included time to engraftment, incidence of graft failure, GVHD, viral reactivation, disease recurrence, and GVHD-free, relapse-free survival (GRFS). Among 24 patients included, median age was 43.5 years (22-62) and a variety of donor types and stem cell sources were represented. At median follow-up of 26.9 months (2.4-72.7), no cases of grade III-IV acute (aGVHD) or severe chronic GVHD (cGVHD) were recorded. Viral reactivation was minimal, and there were no cases of graft failure or PTLD, with 100% disease-free and overall survival at last follow up. The estimate of 1-year GRFS was 86.3% (95% CI: 72.8-100%), with moderate cGVHD accounting for all events. The FCR regimen in SAA was well tolerated, even in older adults, with 100% disease-free survival with low GVHD and infection rates. These encouraging findings should be validated in larger prospective trials.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting.

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and postprotocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, P = .726), documented infection (1.7% versus 6.7%, P = .068), and readmission (13.3% versus 22.7%, P = .091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, P = .736) nor 90-day NRM (0.8% versus 1.3%, P = .736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the preprotocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

How old is too old? Frailty and geriatric assessments of older patients undergoing allogeneic HCT.

Allogeneic hematopoietic cell transplantation (HCT) is a curative-intent treatment for many hematologic malignancies but carries a significant risk of morbidity and mortality. An increasing number of older adults are receiving HCT, but current pretransplant evaluations overlook the unique vulnerabilities that older adults face. Oncology-specific geriatric and frailty assessments provide a comprehensive evaluation of older adults, help better weigh the risks of HCT with patients, and guide personalized optimization strategies to minimize vulnerabilities. Geriatric assessments evaluate seven domains: comorbidities, physical function, mental health, cognition, nutrition, medications, and social support. Frailty indices provide unique evaluations into a patient's overall status. Various standardized measures have been used to evaluate these areas in older adults prior to HCT. Different care models exist for the integration of geriatrics and geriatric principles into HCT evaluation: a multidisciplinary consultative clinic, a geriatrician alongside the HCT clinic, or a primary geriatric hematologist/transplant physician. Future studies are needed to investigate the use of geriatric assessments in selecting the conditioning regimen and intensity and measuring the impact of geriatric assessment-driven interventions on quality of life and toxicities post transplant.

TP53 Mutations Are Associated with Increased Infections and Reduced Hematopoietic Cell Transplantation Rates in Myelodysplastic Syndrome and Acute Myeloid Leukemia.

Although allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy for patients with poor-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), only a minority of these patients undergo HCT. Patients with TP53-mutated (TP53MUT) MDS/AML are at particularly high risk, yet fewer TP53MUT patients undergo HCT compared with poor-risk TP53-wild type (TP53WT) patients. We hypothesized that TP53MUT MDS/AML patients have unique risk factors affecting the rate of HCT and thus investigated phenotypic changes that may prevent patients with TP53MUT MDS/AML from receiving HCT. In this single-center retrospective analysis of outcomes for adults with newly diagnosed MDS or AML (n = 352), HLA typing was used as a surrogate for physician "intent to transplant." Multivariable logistic regression models were used to estimate odds ratios (ORs) for factors associated with HLA typing, HCT, and pretransplantation infections. Multivariable Cox proportional hazards models were used to create predicted survival curves for patients with and those without TP53 mutations. Overall, significantly fewer TP53MUT patients underwent HCT compared to TP53WT patients (19% versus 31%; P = .028). Development of infection was significantly associated with decreased odds of HCT (OR, .42; 95% CI, .19 to .90) and worse overall survival (hazard ratio, 1.46; 95% CI, 1.09 to 1.96) in multivariable analyses. TP53MUT disease was independently associated with increased odds of developing an infection (OR, 2.18; 95% CI, 1.21 to 3.93), bacterial pneumonia (OR, 1.83; 95% CI, 1.00 to 3.33), and invasive fungal infection (OR, 2.64; 95% CI, 1.34 to 5.22) prior to HCT. Infections were the cause of death in significantly more patients with TP53MUT disease (38% versus 19%; P = .005). With substantially more infections and decreased HCT rates in patients with TP53 mutations, this raises the possibility that phenotypic changes occurring in TP53MUT disease may affect infection susceptibility in this population and drastically impact clinical 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.

Reduction in the Prevalence of Thrombotic Events in Sickle Cell Disease after Allogeneic Hematopoietic Transplantation.

Thrombosis is a recognized complication in sickle cell disease (SCD). Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for patients with severe SCD phenotypes. Data describing the effects of allo-HCT on recurrent thrombotic events (venous and arterial events) are limited, however. We evaluated 31 patients with SCD who underwent allo-HCT with a median follow-up of 34.5 months (range, 13 to 115) post-transplantation. No patient continued anticoagulation or antiplatelet therapy after allo-HCT. There was an absolute difference of 32% (95% confidence interval [CI], 12.3% to 32.2%; P = .002) in the prevalence of venous thromboembolic (VTE) events before and after allo-HSCT. In addition, there was an absolute difference of 38.5% (95% CI, 10.63 to 45.96; P = .006) in the number of ischemic cerebrovascular accidents (CVAs) occurring before and after allo-HSCT. Patients with severe SCD who undergo allo-HCT are less likely to develop recurrent thrombotic events compared with a control cohort of patients matched for age and genotype (odds ratio, 0.22; 95% CI, 0.058 to 0.83; P = .025). Following curative therapy with allo-HCT, there is a reduction in recurrent arterial and venous thrombosis in patients with severe SCD phenotypes.

Change in Patients' Perceived Cognition Following Chimeric Antigen Receptor T-Cell Therapy for Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy can lead to durable responses in patients with relapsed/refractory hematologic malignancies. Immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are common and may place patients at risk for longer-term cognitive impairment. This study examined changes in cognition in the first year after CD19-directed CAR T-cell therapy for lymphoma, as well as CAR T-cell therapy-specific risk-factors (e.g., ICANS, CRS) and nonspecific risk factors (e.g., baseline quality of life, frailty) for worsening cognition. Patients' perceived cognition was assessed at baseline and at days 90 and 360. Clinical variables were abstracted from medical records. Piecewise mixed models were used to examine acute change (i.e., within 90 days) and longer-term change (i.e., from 90 days to 360 days) in cognition, as well as to explore risk factors for worsening cognition. Among 118 participants (mean age 61, 59% male), mean levels of perceived cognition did not change from baseline to day 90 (P> .05) but worsened from day 90 to day 360 in global cognition and in the domains of memory, language, organization, and divided attention (P< .05). Although statistically significant, changes were small (d values 0.15-0.28). Greater baseline fatigue, anxiety, and depression were associated with worse global cognition at day 90 (P< .01). Patients with more severe ICANS post-CART reported worse global cognition at day 360 (P< .05), although there were no differences in perceived cognition by severity of CRS (P> .05). Other putative risk factors were not associated with acute or longer-term changes in perceived cognition (P> .05). CAR T-cell therapy recipients reported delayed deterioration in several cognitive domains, although changes were small. These findings may be useful when educating future patients on what to expect when receiving CAR T-cell therapy.

Change in Neurocognitive Performance Among Patients with Non-Hodgkin Lymphoma in the First Year after Chimeric Antigen Receptor T Cell Therapy.

The success of chimeric antigen receptor (CAR) T cell therapy in treating patients with relapsed/refractory hematologic malignancies is leading to a growing number of survivors treated with this regimen. To our knowledge, no previous studies have examined neurocognitive performance in adult CAR T cell therapy recipients, despite high rates of neurotoxicity and cytokine release syndrome (CRS) in the acute treatment period. This study examined changes in neurocognitive performance in the first year after CAR T cell therapy for non-Hodgkin lymphoma (NHL). Putative risk factors for worsening neurocognitive performance (eg, neurotoxicity, CRS) were explored as well. Neurocognition was assessed before initiation of CAR T cell therapy and at 30, 90, and 360 days post-treatment. Clinical variables were abstracted from medical records. Mixed models were used to examine change in total neurocognitive performance (TNP) and cognitive domains (ie, attention, executive function, verbal ability, immediate and delayed memory, and visuospatial abilities). Among 117 participants (mean age, 61 years; 62% male), TNP and executive function declined slightly on average from baseline to day 90 and then improved from day 90 to day 360 (P < .04). Small but significant linear declines in visuospatial ability on average were also observed over time (P = .03). Patients who had 4 or more lines of previous therapy and those with worse neurotoxicity (but not CRS) demonstrated worse TNP. CAR T cell therapy recipients reported transient or persistent deterioration in several cognitive domains, although changes were slight. These findings may be useful when educating future patients on what to expect when receiving CAR T cell therapy.

Association of Patient-Reported Physical Activity on Allogeneic Hematopoietic Cell Transplant Outcomes.

BACKGROUND: Physical function prior to allogeneic hematopoietic cell transplant (HCT) is associated with survival and may be associated with patient physical activity (PA). Tools to evaluate PA prior to HCT are scarce. We aimed to evaluate the impact of easily obtained patient-report of PA prior to HCT on survival. METHODS: HCT recipients between January 1, 2011 and July 5, 2018 and who completed an International Physical Activity Questionnaire Short Form were included. This patient survey captures self-reported activities over the preceding week to determine PA level. RESULTS: We report a retrospective study of 587 adult (age ≥18) HCT recipients. The median age for the cohort was 57.9 years (range 19.9-76.1) with 149 patients (25.4%) age ≥65. Younger patients reported higher PA (low, median age 59.7 years; moderate, 56.1; high, 55.7; p < 0.001). High activity level was reported by males (66.7%; p < 0.001). Patients with low PA had HCT-comorbidity index (HCT-CI) ≥ 3 (68.1%, p = 0.002). When controlling for HCT-CI and disease risk index, higher PA was associated with improved overall survival (HR 0.954, 95% CI 0.921-0.988, p = 0.009). After adjusting for HCT-CI, higher PA was associated with reduced non-relapse mortality (NRM) (HR 0.931, 95% CI 0.891-0.972, p = 0.0013). Subgroup analysis in adults age ≥65 years also found that PA was lower in this population and associated with NRM mortality (HR 0.95, 95% CI 0.90-0.99, p = 0.041). CONCLUSION: Patient-reported PA is a predictor of post-HCT survival. Future studies to validate incorporation of self-report tools to better predict patient-related adverse risk are warranted.

Geriatric Assessment-Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer: A Randomized Clinical Trial.

IMPORTANCE: Although geriatric assessment-driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown. OBJECTIVE: To assess whether specific geriatric assessment-driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial enrolled 613 participants from a National Cancer Institute-designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle. INTERVENTIONS: Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment's domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration. MAIN OUTCOMES AND MEASURES: The primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation. RESULTS: Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, -1.5 to -18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P < .001) was observed. No significant differences were observed in emergency department visits, unplanned hospitalizations, average length of stay, unplanned readmissions, chemotherapy dose modifications or discontinuations, or overall survival. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integration of multidisciplinary GAIN significantly reduced grade 3 or higher chemotherapy-related toxic effects in older adults with cancer. Implementation of GAIN into oncology clinical practice should be considered among older adults receiving chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517034.

Acute patient-reported outcomes in B-cell malignancies treated with axicabtagene ciloleucel.

Chimeric antigen receptor T-cell therapy with axicabtagene ciloleucel (axi-cel) has considerably improved survival in adults with relapsed/refractory large B-cell lymphoma. This study reports patient-reported outcomes (PROs) such as quality of life (QOL) and toxicity in the first 90 days after treatment. Hematologic cancer patients treated with axi-cel (N = 103, mean age = 61, 39% female) completed SF-36 or PROMIS-29 QOL questionnaires prior to treatment and 90 days after. PRO-Common Terminology Criteria for Adverse Events toxicity items were completed by patients at baseline and 14, 30, 60, and 90 days after treatment. Mixed models examined change in PROs over time. From preinfusion to 90 days later, patients reported improvements in physical functioning, pain, and fatigue (ps < 0.01), but worsening of anxiety (p = 0.02). Patient-reported toxicities worsened by day 14 with improvement thereafter. The five most severe symptoms at day 14 included fatigue, decreased appetite, dry mouth, diarrhea frequency, and problems with concentration. Results indicate improvement in some domains of QOL over time with transient patient-reported toxicities.

Breaking the Age Barrier: Physicians' Perceptions of Candidacy for Allogeneic Hematopoietic Cell Transplantation in Older Adults.

Despite continuing increases in the use of allogeneic hematopoietic cell transplantation (alloHCT) in older adults, no standardized geriatric assessment (GA) has been established to risk stratify for transplantation-related morbidity. We conducted a survey of transplant physicians to determine perceptions of the impact of older age (≥60 years) on alloHCT candidacy, and utilization of tools to gauge candidacy. This 23-item online cross-sectional survey was distributed to HCT physicians caring for adults in the United States between May and July 2019. Of the 770 invited HCT physicians, 175 (22.7%) completed the survey. The majority of respondents were age 41 to 60 years and male and practiced in a higher-volume teaching hospital. When considering regimen intensity, 29 physicians (17%) stated they would consider a myeloablative regimen for patients age ≥70 years, and 141 (82%) would consider reduced-intensity/nonmyeloablative conditioning for patients age ≥70 years. Almost all (90%) endorsed the need for a specialized assessment of pre-HCT vulnerabilities to guide candidacy decisions for older adults. Most physicians reported that their centers rarely (33%) or never (46%) use a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates age ≥60 years. Common barriers to performing a GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff. Many alloHCT physicians will consider alloHCT in patients up to age 75 years and not uncommonly in patients older than that. However, the application of tools and domains to assess candidacy in older adults varies widely. Incorporation of a standardized pretransplantation health assessment tool for risk stratification is a significant unmet need.

Use of geriatric assessment in hematopoietic cell transplant.

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.