Depression in patients with hematologic malignancies: The current landscape and future directions.

Patients with hematologic malignancies experience high rates of depression. These patients are vulnerable to depression throughout the disease trajectory, from diagnosis to survivorship, and at the end of life. In addition to the distressing nature of depression, it has substantial downstream effects including poor quality of life, increased risk of treatment complications, and worse survival. Therefore, systematic screening for depression and integration of robust psychological interventions for affected patients is crucial. Although depression has been historically studied mostly in patients with solid malignancies, research focusing on patients with hematologic malignancies is growing. In this article, we describe what is known about depression in patients with hematologic malignancies, including its assessment, prevalence, risk factors, and implications. We also describe interventions to ameliorate depression in this population. Future research is needed to test effective and scalable interventions to reduce the burden of depression among patients with blood cancers.

A multi-cohort phase 1b trial of rituximab in combination with immunotherapy doublets in relapsed/refractory follicular lymphoma.

Antibodies targeting PD-1 or 4-1BB achieve objective responses in follicular lymphoma (FL), but only in a minority of patients. We hypothesized that targeting multiple immune receptors could overcome immune resistance and increase response rates in patients with relapsed/refractory FL. We therefore conducted a phase 1b trial testing time-limited therapy with different immunotherapy doublets targeting 4-1BB (utomilumab), OX-40 (ivuxolimab), and PD-L1 (avelumab) in combination with rituximab among patients with relapsed/refractory grade 1-3A FL. Patients were enrolled onto 2 of 3 planned cohorts (cohort 1 - rituximab/utomilumab/avelumab; cohort 2 - rituximab/ivuxolimab/utomilumab). 3+3 dose escalation was followed by dose expansion at the recommended phase 2 dose (RP2D). Twenty-four patients were enrolled (16 in cohort 1 and 9 in cohort 2, with one treated in both cohorts). No patients discontinued treatment due to adverse events and the RP2D was the highest dose level tested in both cohorts. In cohort 1, the objective and complete response rates were 44% and 19%, respectively (50% and 30%, respectively, at RP2D). In cohort 2, no responses were observed. The median progression-free survivals in cohorts 1 and 2 were 6.9 and 3.2 months, respectively. In cohort 1, higher density of PD-1+ tumor-infiltrating T-cells on baseline biopsies and lower density of 4-1BB+ and TIGIT+ T-cells in on-treatment biopsies were associated with response. Abundance of Akkermansia in stool samples was also associated with response. Our results support a possible role for 4-1BB agonist therapy in FL and suggest that features of the tumor microenvironment and stool microbiome may be associated with clinical outcomes (NCT03636503).

Perspectives on Transfusions for Hospice Patients With Blood Cancers: A Survey of Hospice Providers.

CONTEXT: Patients with blood cancers have low rates of hospice use. While lack of transfusion access in hospice is posited to substantially contribute to these low rates, little is known about the perspectives of hospice providers regarding transfusion access in hospice. OBJECTIVES: To characterize hospice providers' perspectives regarding care for patients with blood cancers and transfusions in the hospice setting. METHODS: In 2022, we conducted a cross-sectional survey of a sample of hospices in the United States regarding their experience caring for patients with blood cancers, perceived barriers to hospice use, and interventions to increase enrollment. RESULTS: We received 113 completed surveys (response rate = 23.5%). Of the cohort, 2.7% reported that their agency always offers transfusions, 40.7% reported sometimes offering transfusions, and 54.9% reported never offering transfusions. In multivariable analyses, factors associated with offering transfusions included nonprofit ownership (OR 5.93, 95% CI, 2.2-15.2) and daily census >50 patients (OR 3.06, 95% CI, 1.19-7.87). Most respondents (76.6%) identified lack of transfusion access in hospice as a barrier to hospice enrollment for blood cancer patients. The top intervention considered as "very helpful" for increasing enrollment was additional reimbursement for transfusions (72.1%). CONCLUSION: In this national sample of hospices, access to palliative transfusions was severely limited and was considered a significant barrier to hospice use for blood cancer patients. Moreover, hospices felt increased reimbursement for transfusions would be an important intervention. These data suggest that hospice providers are supportive of increasing transfusion access and highlight the critical need for innovative hospice payment models to improve end-of-life care for patients with blood cancers.

Mortality among patients with diffuse large B-cell lymphoma and mental disorders: a population-based study.

BACKGROUND: Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking. METHODS: We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates. RESULTS: We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P < .0001). CONCLUSIONS: Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality.

Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: a population-based study.

BACKGROUND: Mental health disorders can potentially decrease quality of life and survival in patients with cancer. Little is known about the survival implications of mental health disorders in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the effect of pre-existing depression, anxiety, or both on survival in a US cohort of older patients with DLBCL. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients aged 67 years or older, diagnosed with DLBCL in the USA between Jan 1, 2001, and Dec 31, 2013. We used billing claims to identify patients with pre-existing depression, anxiety, or both before their DLBCL diagnosis. We compared 5-year overall survival and lymphoma-specific survival between these patients and those without pre-existing depression, anxiety, or both using Cox proportional analyses, adjusting for sociodemographic and clinical characteristics, including DLBCL stage, extranodal disease, and B symptoms. FINDINGS: Among 13 244 patients with DLBCL, 2094 (15·8%) had depression, anxiety, or both disorders; 6988 (52·8%) were female, and 12 468 (94·1%) were White. The median follow-up for the cohort was 2·0 years (IQR 0·4-6·9 years). 5-year overall survival was 27·0% (95% CI 25·1-28·9) for patients with these mental health disorders versus 37·4% (36·5-38·3) for those with no mental health disorder (hazard ratio [HR] 1·37, 95% CI 1·29-1·44). Although survival differences between mental health disorders were modest, those with depression alone had the worst survival compared with no mental health disorder (HR 1·37, 95% CI 1·28-1·47), followed by those with depression and anxiety (1·23, 1·08-1·41), and then anxiety alone (1·17, 1·06-1·29). Individuals with these pre-existing mental health disorders also had lower 5-year lymphoma-specific survival, with depression conferring the greatest effect (1·37, 1·26-1·49) followed by those with depression and anxiety (1·25, 1·07-1·47) and then anxiety alone (1·16, 1·03-1·31). INTERPRETATION: Pre-existing depression, anxiety, or both disorders present within 24 months before DLBCL diagnosis, worsens prognosis for patients with DLBCL. Our data underscore the need for universal and systematic mental health screening for this population, as mental health disorders are manageable, and improvements in this prevalent comorbidity might affect lymphoma-specific survival and overall survival. FUNDING: American Society of Hematology, National Cancer Institute, Alan J Hirschfield Award.

A phase 2 study of pembrolizumab after autologous stem cell transplantation in patients with T-cell non-Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for posttransplantation maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We, therefore, conducted a phase 2 multicenter study of the anti-PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary end point was progression-free survival (PFS) at 18 months after ASCT. Twenty-one patients were treated in this study and 67% (n = 14) completed 8 cycles of treatment. Among all patients who were evaluable, 13 of 21 were alive and achieved PFS at 18 months after ASCT, meeting the study's primary end point. The estimated 18-month PFS was 83.6% (95% confidence interval [CI], 68-100), and overall survival 94.4% (95% CI, 84-100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab, with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02362997.

Interim Positron Emission Tomography During Frontline Chemoimmunotherapy for Follicular Lymphoma.

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1-3A FL who had an interim PET after 2-4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS (P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET (P < 0.001) and progression of disease within 24 months (POD24) (P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS (P < 0.001) or ΔSUVmax75% (P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL.

Minimal residual disease in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation.

Improved biomarkers are required to guide the optimal use of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples, post-ASCT peripheral blood mononuclear cell (PBMC), and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in of 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, P < .001) and inferior overall survival (52% vs 68%, P = .05). The sensitivity and specificity of ASC MRD positivity for progression and death were 36% and 93%, respectively. Positive ASC MRD remained a significant predictor of PFS in multivariable analysis (hazard ratio [HR], 3.7; P < .001). Post-ASCT surveillance MRD testing of plasma, but not PBMC samples, reliably identified patients with an impending relapse. A positive plasma MRD result was associated with inferior PFS (HR, 3.0; P = .016) in a multivariable analysis. The median lead time from MRD detection to relapse was 62 days (range, 0-518 days). In conclusion, the detection of MRD in ASC samples is associated with a very high risk of relapse, justifying alternative treatment strategies or trials of novel consolidation options in these patients. Furthermore, post-ASCT MRD monitoring may facilitate the evaluation of the early initiation of treatment at molecular relapse. This trial has been registered at www.clinicaltrials.gov as #NCT02362997.

Correlates of common concerns in older cancer survivors of leukemia and lymphoma: results from the WHI LILAC study.

PURPOSE: Older survivors of leukemia and lymphoma often experience long-term effects of chemotherapy. We described common concerns related to their cancer and treatment in older survivors of leukemia and non-Hodgkin lymphoma (NHL) and assessed correlates of these concerns. METHODS: We utilized data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited post-menopausal women aged 50-79. Participants diagnosed with leukemia and NHL were included (n = 420). They were asked about 14 areas of current concerns related to their cancer and treatment and to rate each from 0 (no concern) to 2 (major concern), with total scores ranging from 0 to 28. Linear regression was used to assess factors correlated with the concern score, and logistic regression for factors correlated with the three most common concerns. RESULTS: Mean age at assessment was 81 years (range 69-99); 72% reported at least one concern, and median concern score among these survivors was 3.5 (Q1-Q3 2-5). Factors significantly correlated with concern scores were sadness, pain, distress, higher prior symptom count, and loneliness (all p < 0.05). Significant factors correlated with common concerns were (1) fatigue/sleep: sadness/depression, distress, higher prior symptom count, greater loneliness, and worse physical functioning; (2) physical functioning/activity: older age, public insurance, higher body mass index, pain, worse QoL, and higher treatment-related comorbidities; (3) memory/concentration: prior chemotherapy or radiation, worse QoL, higher prior symptom count, and greater loneliness (all p < 0.05). CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Almost three-quarters of older survivors of leukemia and lymphoma reported at least one concern; a multifaceted intervention may be needed to address these concerns.

Sequencing therapy in relapsed DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy worldwide, comprising approximately 30% of all lymphomas. Currently, 50% to 60% of patients diagnosed with DLBCL are alive at 5 years and cured with modern therapy, but about 10% to 15% of patients are refractory to first-line therapy, and an additional 20% to 30% relapse following a complete response. Patients who have relapses beyond 2 years may experience more favorable outcomes and have forms of DLBCL that can be distinguished biologically. Patients who experience early relapse or who have primary refractory disease (less than a complete response or relapse within 3 to 6 months of initial therapy) have worse outcomes. For decades, the standard of care treatment strategy for fit patients with relapsed DLBCL has been salvage therapy with non-cross-resistant combination chemoimmunotherapy regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) as stem cell rescue for patients with chemosensitive disease. Recent data suggest that certain patients may benefit from chimeric antigen receptor T-cell therapy (CAR T) in the second-line setting. Additional novel therapies exist for patients who are ineligible, who are unable to access these therapies, or who fail ASCT and/or CAR T. Despite the advent of new therapies for DLBCL and improved outcomes, DLBCL remains a life-threatening illness. Thus, it is essential for clinicians to engage in serious illness conversations with their patients. Goals-of-care communication can be improved through skills-based training and has been demonstrated to have an impact on patient experiences.

Prognostic value of minimal residual disease among patients with classical Hodgkin lymphoma undergoing autologous stem cell transplantation.

Improved biomarkers are needed to guide patient selection for autologous stem cell transplantation (ASCT) and post-ASCT maintenance therapies in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the prognostic value of minimal residual disease (MRD) using immunoglobulin-based high-throughput sequencing (Ig-HTS), we analyzed pre- and post-ASCT peripheral blood and pre-ASCT apheresis stem cell (ASC) samples in 36 cHL patients. A tumor clonotype was detected in only 12 patients (33%). Among these patients, MRD within plasma samples was closely associated with impending relapse. All patients (n = 3) with detectable MRD in any post-ASCT plasma sample relapsed (100% specificity), and MRD was not detected in any patients in remission. MRD testing from cellular specimens (peripheral blood mononuclear cell or ASC samples) was not associated with relapse. In this small cohort, plasma-based MRD testing appeared to be a promising biomarker in cHL, but given low clonotype detection rates with Ig-HTS, alternative MRD approaches should be investigated.

Patient, Family, and Clinician Perspectives on Location of Death for Adolescents and Young Adults With Cancer.

PURPOSE: Adolescents and young adults (AYAs) with cancer have high rates of hospital deaths. It is not clear if this reflects their preferences or barriers to dying at home. METHODS: Between December 2018 and January 2021, we conducted in-depth interviews with AYAs (age 12-39 years) with stage IV or recurrent cancer, family caregivers including bereaved caregivers, and clinicians of AYAs with cancer. Patients were asked about their priorities for care including location of death, caregivers were asked what was most important in the care of their AYA family member, and clinicians were asked to reflect on priorities identified through caring for AYAs. Directed content analysis was applied to interview data, and themes regarding location of death were developed. RESULTS: Eighty individuals (23 AYAs, 28 caregivers, and 29 clinicians) participated in interviews. Most AYAs and caregivers preferred a home death. However, some AYAs and caregivers opted for a hospital death to alleviate caregiver burden or protect siblings from the perceived trauma of witnessing a home death. Lack of adequate services to manage intractable symptoms at home and insufficient caregiver support led some AYAs/caregivers to opt for hospital death despite a preference for home death. Participants acknowledged the value of hospice while also pointing out its limitations in attaining a home death. CONCLUSION: Although most AYAs prefer to die at home, this preference is not always achieved. Robust home-based services for effective symptom management and caregiver support are needed to close the gap between preferred and actual location of death for AYAs.

End-of-Life Care for Older Adults with Aggressive Non-Hodgkin Lymphoma.

Background: Aggressive non-Hodgkin lymphoma (NHL) commonly affects older adults and is often treated with intensive therapies. Receipt of intensive therapies and absence of a clear transition between the curative and palliative phases of treatment yield prognostic uncertainty and risk for poor end-of-life (EOL) outcomes. However, data regarding the EOL outcomes of this population are lacking. Methods: We conducted a retrospective analysis of adults ≥65 years with aggressive NHL treated with systemic therapy at Massachusetts General Hospital from April 2000 to July 2020 who subsequently died. We abstracted patient and clinical characteristics and EOL outcomes from the medical record. Using multivariable logistic regression, we examined factors associated with hospitalization within 30 days of death and hospice utilization. Results: Among 91 patients (median age = 75 years; 37.4% female), 70.3% (64/91) were hospitalized, 34.1% (31/91) received systemic therapy, and 23.3% (21/90) had an intensive care unit admission within 30 days of death. The rates of palliative care consultation and hospice utilization were 47.7% (42/88) and 39.8% (35/88), respectively. More than half of patients (51.6%, 47/91) died in a hospital or health care facility. In multivariable analysis, elevated lactic acid dehydrogenase was associated with risk of hospitalization within 30 days of death (odds ratio [OR] 3.61, p = 0.014). Palliative care consultation (OR 4.45, p = 0.005) was associated with a greater likelihood of hospice utilization, whereas hypoalbuminemia (OR 0.29, p = 0.026) was associated with a lower likelihood of hospice utilization. Conclusions: Older adults with aggressive NHL often experience high health care utilization and infrequently utilize hospice care at the EOL. Our findings underscore the need for interventions to optimize the quality of EOL care for this population.

Immune Reconstitution following High-Dose Chemotherapy and Autologous Stem Cell Transplantation with or without Pembrolizumab Maintenance Therapy in Patients with Lymphoma.

Autologous stem cell transplantation (ASCT) is a standard of care for patients with chemosensitive, relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and diffuse large B cell lymphoma (DLBCL). Whereas the clinical benefit of ASCT has traditionally been attributed solely to cytoreduction from intensive chemotherapy, ASCT has important immunogenic effects that may contribute to its antitumor efficacy and could provide a favorable immune environment for post-ASCT immune-based maintenance treatments. We previously reported clinical results of a phase II trial (ClinicalTrials.gov identifier NCT02362997) testing 8 doses of pembrolizumab maintenance therapy after ASCT for patients with R/R cHL or DLBCL. To clarify the impact of pembrolizumab on immune reconstitution, we compared the kinetics of peripheral blood immune cell recovery after ASCT for trial patients receiving pembrolizumab maintenance to those of a contemporaneous control cohort of similar patients undergoing ASCT without pembrolizumab maintenance. This study was conducted to characterize the impact of post-ASCT pembrolizumab maintenance therapy on immune reconstitution for patients with R/R DLBCL and cHL and to identify candidate biomarkers of efficacy and immune-related adverse events (irAEs). Peripheral blood (PB) mononuclear cell samples were prospectively collected at 1 to 18 months after ASCT and analyzed by flow cytometry using a panel of fluorophore-conjugated monoclonal antibodies to identify B cells, natural killer (NK) cells, and various dendritic cell (DC) and T cell subsets. A median of 5 (range, 1 to 8) post-ASCT PB samples were collected from 144 patients (59 in the pembrolizumab group and 85 in the control group). Clinical characteristics of the 2 cohorts were similar. Compared with cHL patients, DLBCL patients (all of whom received anti-CD20 monoclonal antibody therapy before ASCT) had delayed CD19+ cell reconstitution that persisted for at least 18 months after ASCT. No other differences in immune reconstitution based on lymphoma subtype were observed. Post-ASCT pembrolizumab maintenance therapy was associated with an elevation in circulating DCs (driven by higher levels of plasmacytoid and immature DCs) that persisted for the duration of pembrolizumab treatment, along with a significant reduction in PD-1+ T cells that persisted for 6 to 12 months after completion of pembrolizumab therapy. Despite the key role of T cells in mediating the effects of PD-1 blockade, pembrolizumab maintenance did not affect recovery of any T cell subsets. In an exploratory analysis, a higher baseline CD4+ terminal effector memory cell count (defined as CD3+CD4+CD45RA+CD62L-) was associated with inferior progression-free survival (PFS), but only among patients who received pembrolizumab maintenance (P = .003). As continuous variables, lower absolute levels of NK cells (P = .009), PD-1+ CD4+ T cells (P = .005), and PD-1+ CD8+ T cells (P = .005) before pembrolizumab initiation were each associated with a higher risk of grade 2+ irAEs. Our findings indicate that post-ACST pembrolizumab maintenance therapy is associated with a persistent elevation of circulating DCs, but its impact on the reconstitution of other immune cells in peripheral blood appears limited. Our study suggests that early features of post-ASCT immune reconstitution could be associated with PFS and the risk of irAE and warrant additional investigation. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Precancer and cancer-associated depression and anxiety among older adults with blood cancers in the United States.

For patients with blood cancers, comorbid mental health disorders at diagnosis likely affect the entire disease trajectory, as they can interfere with disease information processing, lead to poor coping, and even cause delays in care. We aimed to characterize the prevalence of depression and anxiety in patients with blood cancers. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients ≥67 years old diagnosed with lymphoma, myeloma, leukemia, or myelodysplastic syndromes between 2000 and 2015. We determined the prevalence of precancer depression and anxiety and cancer-associated (CA) depression and anxiety using claims data. We identified factors associated with CA-depression and CA-anxiety in multivariate analyses. Among 75 691 patients, 18.6% had at least 1 diagnosis of depression or anxiety. Of the total cohort, 13.7% had precancer depression and/or precancer anxiety, while 4.9% had CA-depression or CA-anxiety. Compared with patients without precancer anxiety, those with precancer anxiety were more likely to have subsequent claims for CA-depression (odds ratio [OR] 2.98; 95% CI 2.61-3.41). Other factors associated with a higher risk of CA- depression included female sex, nonmarried status, higher comorbidity, and myeloma diagnosis. Patients with precancer depression were significantly more likely to have subsequent claims for CA-anxiety compared with patients without precancer depression (OR 3.01; 95% CI 2.63-3.44). Female sex and myeloma diagnosis were also associated with CA-anxiety. In this large cohort of older patients with newly diagnosed blood cancers, almost 1 in 5 suffered from depression or anxiety, highlighting a critical need for systematic mental health screening and management for this population.

Prognostic value of disease risk score versus gait speed in older adults with lymphoma.

Measures of physical function predict survival in older patients with lymphoma but their prognostic ability has not been compared to disease-specific risk scores. We prospectively recruited patients ≥75 years with lymphoma. Patients underwent a frailty screen including 4-m gait speed. Disease-specific risk scores were obtained retrospectively. Among 168 patients, there was no association between disease-specific risk score and survival. Conversely, faster gait speed was significantly associated with survival in the entire cohort (HR = 0.16; 95%CI, 0.06-0.42; p = 0.0003) indicating a HR of 0.63 for an increase in gait speed of 0.25 m/s. When gait speed was added to the DLBCL IPI and FLIPI separately, it was significantly associated with OS (p = 0.004 for DLBCL, p = 0.03 for FLIPI) which increased its predictive power. Our study of older lymphoma patients demonstrates gait speed may improve outcome prediction beyond standard prognostic scores.

Goal of a "Good Death" in End-of-Life Care for Patients with Hematologic Malignancies-Are We Close?

PURPOSE OF REVIEW: The medical field has a critical role not only in prolonging life but also in helping patients achieve a good death. Early studies assessing end-of-life quality indicators to capture if a good death occurred demonstrated low rates of hospice use and high rates of intensive healthcare utilization near death among patients with hematologic malignancies, raising concerns about the quality of death. In this review, we examine trends in end-of-life care for patients with hematologic malignancies to determine if we are close to the goal of a good death. RECENT FINDINGS: Several cohort studies show that patients with blood cancers are often inadequately prepared for the dying process due to late goals of care discussions and they experience low rates of palliative and hospice care. More recent analyses of population-based data demonstrate some improvements over time, with significantly more patients receiving palliative care, enrolling in hospice, and having the opportunity to die at home compared to a decade ago. These encouraging trends are paradoxically accompanied by concomitant increases in late hospice enrollment and intensive healthcare utilization near death. Although we are closer to the goal of a good death for patients with hematologic malignancies, there is ample room for growth. To close the gap between the current state of care and a good death, we need research that engages patients, caregivers, hematologic oncologists, and policy-makers to develop innovative interventions that improve timeliness of goals of care discussions, expand palliative care integration, and increase hospice use.

Gait speed, survival, and recommended treatment intensity in older adults with blood cancer requiring treatment.

BACKGROUND: Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' "gestalt" assessments. METHODS: Gait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN-based categorizations of oncologists' treatment intensity recommendations, including gait speed. RESULTS: The median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4-0.6 m/s), 34.0 months (0.6-0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6-0.8 m/s: HR, 1.76; 0.4-0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity. CONCLUSION: In older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection.

Strategies for introducing palliative care in the management of relapsed or refractory aggressive lymphomas.

Recent advances in treatment of patients with aggressive lymphomas ranging from chimeric antigen receptor T-cell therapy to combination of antibody-drug conjugates with chemotherapy have improved survival outcomes. Despite these significant advances, patients with relapsed or refractory disease experience high physical and psychological symptom burden, and a substantial proportion still die of their lymphoma. In addition, end-of-life care outcomes are suboptimal with high rates of intensive end-of-life health care use and low rates of timely hospice enrollment. Integrating palliative care concurrently with disease-directed care for this patient population has strong potential to improve their symptom burden, quality of life, and end-of-life care. Multiple factors, including heightened prognostic uncertainty in the setting of relapsed/refractory disease, pose challenges to timely provision of palliative care. This article reviews benefits of primary and specialty palliative care for patients with relapsed/refractory aggressive lymphomas and barriers to such care. It also highlights strategies for effectively integrating palliative care for patients with relapsed/refractory aggressive lymphomas.