Research articles related to the physical, psychological, social, and spiritual well-being of patients with non-Hodgkin lymphoma (NHL) and their caregivers published between January 2021 and December 2023 were analyzed to provide an evidence base for the development of integrative education tools to empower patients and their caregivers following an NHL diagnosis and throughout the continuum of care.
A total of 12,645 articles were identified in the screen, 935 full-text publications were reviewed, and 118 relevant articles were identified. The results of the analysis are described in detail below.
We performed a comprehensive search of the published scientific literature for the physical, psychological, social, and spiritual well-being of patients diagnosed with NHL and their caregivers in the past 3 years (2021-2023). An overview of the methodology utilized for the specific end points is provided in detail below.
To identify published review articles relevant to physical, psychological, social, and spiritual well-being of patients diagnosed with NHL and their caregivers, the PubMed database was searched using the following parameters:
– Physical well-being
– Psychological well-being
– Social well-being
– Spiritual well-being
Publications were categorized based on the following parameters:
The following analyses were conducted:
A total of 935 articles met the search criteria and limits described above. After thoroughly screening all titles and abstracts for relevance, 118 relevant articles were identified and included in the gap analysis (Table). Each of the 4 domains had a unique subset of search terms, but many publications were identified through multiple relevant search terms under multiple domains. The 118 publications were reviewed and grouped by topic to identify relevant themes in the support of patients with NHL and their caregivers.
Publications are categorized by publication year in Figure 1. Publications are categorized by domain and their overlap of relevance in Figure 2. Of articles that were identified in only a single search, the majority were in physical (n=69), followed by social (n=5), psychological (n=3), and spiritual (n=0).
The following section provides a detailed discussion of each analysis categorized by common themes.
Among the 118 relevant articles analyzed, many were identified multiple times across search terms and domains. Deeper examination of the relevant publications found that single articles often addressed multiple themes that spanned several domains. While most articles with overlap were identified when searching subcategories within the physical domain, many included insights into the social, psychological, and spiritual impacts of the physical term (for example, the cognitive impact of a particular treatment may have appeared in searches within the psychological domain and the physical domain), and thus were returned in those searches as well. Here we summarize the common themes that arose from this literature analysis.
There are a variety of patient and disease characteristics that are directly correlated with the outcomes and prognoses for patients with NHL. These outcomes include hospital readmission, mortality, response to therapy, and other parameters.1-5 At the beginning of a patient’s journey, delayed and/or inaccurate diagnosis of NHL contributes adversely to patient morbidity and mortality. Accurate imaging with CT, integrated PET-CT, and MRI is crucial to improving long-term outcomes.6 Chronic illness also affects patient prognosis. Diabetes mellitus is associated with poor survival outcomes; however, treatment with metformin may offer some improvement.3 As with many critical illnesses, hyponatremia is a predictor of poor outcomes in those with NHL-associated hemophagocytic lymphohistiocytosis.4 Malnutrition may arise as a consequence of lymphoma and negatively affect the response to therapy.1 Many patients with NHL have genetic risk factors for venous thromboembolic events (VTE), posing a threat to their long-term health and survival. A predictive tool, the TiC-LYMPHO score, can categorize patients with lymphoma in terms of their risk of VTE, thus allowing for better and more individualized thromboprophylaxis.7
Some types of NHL have a particularly poor prognosis in specific populations. Primary central nervous system lymphoma (PCNSL) has a very poor prognosis in the elderly8 and among Black patients.9 Age at diagnosis, sex, histology, tumor site, surgery, chemotherapy, and marital status were independent prognostic factors of overall survival from PCNSL.9 Those with follicular lymphoma (FL) who experience early relapse or transition to aggressive lymphoma also have particularly poor outcomes.10 Adolescent and young adult patients with NHL residing in lower- income counties in the United States are at increased risk of death.11 Interestingly, certain times of year, such as the holidays, are also associated with an increased risk of mortality in various cancer types.12
Diagnosis and treatment at older age present specific challenges for those with NHL. For this population, toxicity related to therapy may be increased, along with in-hospital mortality, hospital length of stay, and hospitalization costs.13-15 In older patients with B-cell NHL, R-CHOP regimens in particular are associated with an increased risk of bone fracture.16 Older adults with aggressive NHL often have high healthcare utilization yet infrequently use hospice at the end of life. Supportive care interventions could enhance the care experience for older adults and optimize end-of-life quality and care.15,17 Data to address challenges related to treating older patients with NHL can be limited, as older adults tend to have less clarity around clinical trial goals, which impacts enrollment and access to new potential therapeutics.18
The wide variety of NHL subtypes presents researchers and practitioners with a seemingly unending battle to refine and optimize therapies. Though there is a shortage of literature directly comparing evidence on the efficacy and safety of various first-line therapies for mantle cell lymphoma (MCL), a systematic literature review showed that it remains a difficult NHL subtype to treat, with short survival highlighting the unmet need for newer treatments that improve patient outcomes.19 The past decade has brought new agents in the treatment of relapsed and/or refractory (R/R) MCL, including Bruton’s tyrosine kinase (BTK) inhibitors. Unfortunately, BTK resistance is common, leading to a need for novel agents.20 In patients with diffuse large B-cell lymphoma (DLBCL), single-agent selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance, regardless of prior therapy and disease-refractory status.21
Relapse remains a significant treatment hurdle for patients with NHL, especially for those who relapse in the 24 months following completion of chemoimmunotherapy. Optimal management of these cases has yet to be determined.
Relapse remains a significant treatment hurdle for patients with NHL, especially for those who relapse in the 24 months following completion of chemoimmunotherapy. Optimal management of these cases has yet to be determined, although expanded use of approved agents and other therapeutics in the clinical pipeline provide hope to patients and their families.22 FL is the most common indolent lymphoma, and while it is highly responsive to therapy, the majority of patients suffer multiple relapses. A host of new antibody-based agents are now available, including tafasitamab, polatuzumab vedotin, and magrolimab, all of which target macrophages rather than FL cells directly. Lenalidomide has moved to earlier lines of therapy, and apoptotic pathway modulators show promise, as does CAR T-cell therapy (CAR T). Given these multiple potentially non–cross-reactive mechanisms, studies of rationally designed combination strategies hold the promise of improving outcomes and possibly curing FL.23
CAR T has changed the treatment paradigm for many NHL subtypes. For patients with R/R aggressive B-cell NHL, CAR T has shown impressive response rates and the possibility for a durable remission.24 Adverse reactions are generally controllable, and patients who see a complete response after CAR T or survive for 1 year after therapy may have better long-term survival.25 Incorporating bridging radiation therapy before CAR T has been associated with improved local control compared with salvage radiation therapy implemented after CAR T.26 In addition, CAR T has shown compelling real-world overall survival for those with R/R double-hit lymphoma.27 It is an effective therapy in older adults, although toxicities may be amplified in this population.13 Interestingly, therapeutic response to CAR T has been associated with the health of the patient’s gut microbiome.28 Barriers to CAR T include cost of therapy, patient hesitancy, required travel to academic treatment centers, nonreferrals, poor understanding of CAR T, lack of caregiver support, knowledge of available resources, and timely patient selection by referring oncologists.29
Unfortunately, CAR T failure does occur, leaving patients with very poor prognoses and limited treatment options.30 A 2023 study showed that PET/CT-derived R-signature could be a potential prognostic biomarker for R/R DLBCL patients undergoing CAR T.31 Contrast-enhanced CT-based radiomic features may predict disease progression in R/R B-cell NHL within the 6 months following CAR T.32 Almost one-quarter of CAR T recipients are readmitted within the first 30 days. Transfer to a facility at discharge, chronic renal disease, cerebrovascular disease, and noninvasive ventilation were associated with higher odds of readmission, while admission to a teaching hospital lowered the odds of readmission.2 About half of patients with aggressive B-cell NHL who progress after anti- CD19 CAR T are subsequently excluded from clinical trials, presenting a significant barrier to trial enrollment.33
Treatment-related adverse events (AEs) in patients being treated for NHL vary by type of lymphoma and by therapeutic approach. High-dose chemotherapy is frequently administered to patients with hematologic malignancies, resulting in severe adverse drug reactions at a relatively high frequency.34 While radioimmunotherapy has shown promising results in several clinical studies in different populations and types of NHL, it has been associated with secondary neoplasms (acute myeloid leukemia) as well as myelodysplastic syndrome.35 Use of immune checkpoint inhibitors (ICIs) has increased, as has the incidence of immune-related AEs. While these AEs were actually associated with better long-term survival in NHL treated with ICIs, patients’ disease conditions should be carefully evaluated to determine optimal management with these drugs.36 Medication instruction sheets have been developed for patients receiving various treatment regimens (R-CHOP, ESHAP±R) and show promise as valuable tools for monitoring adverse drug reactions.34,37 The number of cancer patients (including those with NHL) receiving myelosuppressive chemotherapy regimens with high risk for febrile neutropenia has increased since 2005, as has the use of prophylactic colony-stimulating factors. The incidence of neutropenia-related hospitalization has increased slightly, particularly among NHL patients.38 In addition to managing AEs, hematology-oncology nurses play a vital role in teaching patients and their caregivers about the side effects of cancer treatment, including infection risks, appropriate skin care, and other ways to maintain quality of life (QOL) throughout treatment.39
Gastrointestinal toxicities (nausea, vomiting, oral mucositis, and dysphagia) are common with NHL treatments and can result in poor study compliance, although these AEs can often be effectively mitigated with appropriate treatment. The incidence of diarrhea was lower for patients receiving enterade compared with placebo (16% vs 86%, P<.03).40 Treatment with netupitant/palonosetron combination therapy, administered every other day, was effective in preventing chemotherapy-induced nausea and vomiting in patients at high risk of gastrointestinal effects while undergoing chemomobilization of hematopoietic stem cells prior to autologous stem cell transplantation (ASCT).41
Severe CRS is the most significant and life-threatening adverse effect of CAR T. An individual’s risk of developing CRS is an important factor for patients and care teams evaluating CAR T as a treatment choice, second only to the probability of 1-year survival.42 Recent research has yielded a nomogram that can predict which patients are likely to develop severe CRS before they become critically ill.43
While it is not entirely clear what causes CRCI, lactate production and Warburg metabolism may impact neurotransmitter dysregulation and neurocognition in central nervous system lymphomas.
Many individuals receiving treatment for NHL report cognitive adverse effects, both during and after treatment. A study by Gates et al showed that it is feasible to longitudinally assess cancer-related cognitive impairment (CRCI) in patients with lymphoma from diagnosis through recovery and beyond, and that these interactions also improved patient experiences and cognitive outcomes.44 This study also achieved sustained participation and retention of patients undergoing standard treatment by minimizing the logistical demands of data collection, having clinicians included, making the tasks interesting, and providing empathetic support to the patient throughout.45 Patients with NHL who received CAR T reported transient or persistent deterioration in several cognitive domains, and although changes were slight, these findings can be useful when educating newly diagnosed patients on what to expect when receiving CAR T.46 While it is not entirely clear what causes CRCI, lactate production and Warburg metabolism may impact neurotransmitter dysregulation and neurocognition in central nervous system (CNS) lymphomas. Understanding the interactions between lymphoma metabolism, neurotransmitter imbalance, and neurocognition may promote interventions that preserve cognitive function.47
Some treatments for NHL come with a risk of significant cardiovascular AEs, and patients should be counseled appropriately on their personal likelihood of developing disorders of the heart and vascular system. Cancer treatment contributed more to heart disease, chronic obstructive pulmonary disease, and chronic kidney disease than lifestyle factors and comorbidities in a study of B-cell NHL survivors.48 Monoclonal antibody treatments, such as trastuzumab and rituximab, may be associated with the development of cardiotoxicity, and more studies are needed to investigate the association of risk factors induced by these treatments and to create strategies to prevent and manage these effects.49 Patients with cardiovascular risk factors have a higher risk of subsequent myocardial infarction if they have mediastinal radiation, so routine evaluation and optimal treatment of preexisting cardiovascular disease should continue after receiving cancer therapy. Mediastinal radiation should only be used in these patients if the oncologic benefit clearly outweighs the risk of cardiovascular harm.50 Assessment and analysis of myocardial work in patients with NHL can diagnose subclinical cardiotoxicity and predict events such as left ventricle ejection fraction decline, and appropriate parameters should be used for evaluation of myocardial function during chemotherapy.51
Physical activity and body composition play a crucial role in overall health, but their role in NHL risk and recovery is less clear. Studies have found no effect of physical activity on the risk of lymphoma and its subtypes overall. While there is an observed inverse association of occupational and total physical activity with risk of lymphoma (all subtypes) and B-cell NHL among women, there was an upward trend in risk of Hodgkin’s lymphoma with recreational and physical activity among men.52 However, a pooled analysis from 9 case-control studies to examine the association between moderate-to-vigorous intensity physical activity and risk of NHL overall and by subtype shows physical activity is associated with a modest risk reduction for NHL.53 Body composition plays a role in recovery; high pretransplant visceral adipose tissue density was associated with lower overall survival and higher nonrelapse mortality, and low pretransplant visceral adipose tissue was associated with worse relapse-free survival in patients with NHL undergoing autologous hematopoietic stem cell transplantation.5
Frailty in particular was associated with greater in-hospital mortality, longer length of stay, and higher hospitalization costs among patients with lymphoid malignancies undergoing autologous hematopoietic stem cell transplantation.
Nutrition and frailty have a significant impact on outcomes for patients with NHL. There is increasing evidence that malnutrition, sarcopenia, and cachexia in lymphoma are intimately interrelated and are hallmarks of frailty and poor outcomes.1 For patients with NHL, the Global Leadership Initiative on Malnutrition criteria could be applied as an effective replacement to the Patient-Generated Subjective Global Assessment for nutrition assessment and mortality prediction, especially for predicting long-term prognostic outcomes.43 Frailty in particular was associated with greater in-hospital mortality, longer length of stay, and higher hospitalization costs among patients with lymphoid malignancies undergoing autologous hematopoietic stem cell transplantation; comprehensive health status assessments for identifying and managing frail patients could improve outcomes.14 Unfortunately, the therapeutics used to treat NHL are themselves often responsible for malnutrition. Most patients with lymphoproliferative neoplasms do not show clinical or biochemical symptoms of malnutrition before therapy but show subsequent deterioration of nutritional status after initiation of cancer treatments.54
Patients diagnosed during pregnancy must also be counseled on the treatment options available and offered ongoing support. A study of maternal and neonatal outcomes of pregnant patients diagnosed with DLBCL between 1986 and 2019 showed that standard treatment can be offered to pregnant patients in obstetric centers that cater to high-risk patients.55 A systematic review showed that the administration of systemic chemotherapy in the second and third trimesters was not associated with an increased rate of congenital malformations or perinatal mortality, with maternal outcomes broadly comparable to those of the nonpregnant population.56 Although studies have examined efficacy and safety of chemoimmunotherapy for mothers treated in the second and third trimesters, further data are needed to establish recommendations for medical management of patients with aggressive NHL in their first trimester of pregnancy.57 Women with lymphoma in pregnancy valued clear and empathic communication, provision of tailored educational materials, access to psychosocial supports (particularly childcare and financial supports), and timely oncofertility management in their healthcare journey.58
Those living with HIV are at an increased risk for NHL and other malignancies. In addition, people with HIV have higher mortality rates after developing cancer. NHL, Kaposi sarcoma, and anal and lung cancers are large contributors to years of life lost to cancer in the HIV population in the United States.59 Among those with HIV and NHL, HIV status, CD4+ lymphocyte count, and R/R disease state affected survival; treatments such as rituximab did not appear to improve outcome in HIV-related lymphomas.60 HIV status among hospitalized ASCT recipients with lymphoid malignancies did not impact adverse hospital outcomes; however, the rates of ASCT were substantially lower among Black people living with HIV.61 Improved access to antiretroviral treatments, cancer prevention, and screening have the potential to reduce cancer mortality in those with HIV.59
Since 2020, the COVID-19 pandemic has highlighted the challenges and risks posed by infectious disease for those with NHL. Patients with NHL are immunocompromised due to impaired humoral and cellular immunity and are also prescribed immunosuppressive therapy, resulting in an elevated risk for severe COVID-19 infection.62,63 Vaccination, while a key component of COVID-19 prevention, does not illicit the same immune response in patients with NHL as it does in healthy individuals. While antibody response to RNA-based COVID-19 vaccines is already reduced in patients with NHL, treatment with rituximab/obinutuzumab, anti-CD20 antibody therapy, and CAR T has been shown to further reduce the humoral response to these vaccines.62-66 These findings suggest that those with NHL be prioritized for booster doses, and one study suggests that vaccination occur before treatment initiation, if possible.65 Among patients with NHL who are hospitalized for COVID-19, age ≥70 years, R/R lymphoma, and recent administration of anti-CD20 therapy are risk factors for prolonged length of stay and death.67
Maintaining quality of life, both while battling NHL and after, continues to be at the forefront of research. In patients with lymphoproliferative neoplasms, clinicians observe improvement in overall QOL and level of functioning after the first-line treatment as the severity of symptoms is reduced.68 Cancer-related fatigue is a common complaint among patients and has been correlated with circadian disruptions and sleep quality. However, new data show no indications for association between chronotype and fatigue, leading researchers to conclude that fatigue is more likely associated with self-reported sleep quality rather than with chronotype.69 Older patients with NHL face unique challenges, but upon multivariate analysis, only frailty status, depression status, and ECOG performance score (factors in the Comprehensive Geriatric Assessment) have a statistically significant relationship to health-related QOL (HRQOL) in patients older than 60 years.70
New management tools are in development to help practitioners monitor AEs and improve overall QOL during treatment and beyond. The European Organisation for Research and Treatment of Cancer Quality of Life Group has developed 2 internationally validated questionnaires on HRQOL, data from which can be used by patients and clinicians to better evaluate treatment options and determine the best choices for the patient.71 The Advanced Symptom Management System for remote symptom monitoring in cancer care led to a significant reduction in symptom burden for patients. Such systems show a sizable, positive clinical effect on patients’ symptom experiences, and remote monitoring systems will be vital for future services, particularly in blended models of care delivery resulting from the COVID-19 pandemic.72 A new medication guidance sheet for monitoring AEs from chemotherapy is becoming a useful tool for predicting occurrence and timing of events for cancer patients, including those with NHL.37 Provider training on recognizing threats to and addressing HRQOL is also critical. A review of studies of patients with PCNSL shows that nurses play a vital role in maintaining QOL during treatment and recommends a focus on early recognition and comprehensive management of neurologic symptoms. This should include both patient and caregiver education as well as diligent implementation of treatment strategies to maximize QOL.73
In studies of patients with indolent NHL on active surveillance, HRQOL is globally preserved for up to 3 years after diagnosis, but emotional well-being continues to be an unmet need during this stage of their disease.
Managing threats to HRQOL requires a delicate balance of interventions. Active surveillance (as opposed to cancer-directed treatment) in patients battling NHL/chronic lymphocytic leukemia may actually have negative implications for patient QOL, despite the fact that both active surveillance and cancer-directed approaches share the goal of delaying the impact of treatments (eg, appointments, toxicities) on QOL.74 In studies of patients with indolent NHL (iNHL) on active surveillance, HRQOL is globally preserved for up to 3 years after diagnosis, but emotional well-being continues to be an unmet need during this stage of their disease.75 Providing self-management support to those diagnosed with low-grade NHL is relevant given the chronic trajectory of the disease; these support tools should include regular review with monitoring and practical support around facilitating engagement with social networks.76
Due to advances in NHL treatment, the number of long-term NHL survivors is increasing dramatically. Patients need a survivorship plan that addresses a range of concerns, including QOL and uncertainty about the future, possible physical health complications (including cardiovascular disease, infertility, and subsequent neoplasms), and the impact of novel NHL treatments and their potential complications (CAR T, immunotherapies, etc).77 Long-term survivors of childhood NHL tend to have a good overall health status, with no significant differences compared with the general population. Age at initial diagnosis is the main demographic factor that affects patients’ later QOL.78 Nurses appear to play a deeply impactful role in the overall well-being of young adults receiving active treatment for lymphoma, but more research is necessary to understand the experiences of these patients through extended or long-term survivorship.79 Self-reported survey data from long-term survivors of indolent lymphoma showed that somatic comorbidities, not working for pay, and chronic fatigue were significantly associated with reduced physical HRQOL. Almost three-quarters of older survivors of leukemia and lymphoma reported at least 1 concern related to the cancer and/or treatment; a multifaceted intervention may be needed to address these concerns.80
NHL survivors reported poorer QOL, primarily related to depression symptoms, fear of cancer recurrence, higher illness burden (ie, comorbidity), and fewer personal resources (ie, unemployed), whereas fear of cancer recurrence was related to shorter time since diagnosis and more depressive symptoms. Fear of cancer recurrence and depressive symptoms may adversely impact QOL, and recent diagnosis and depression-related pessimism may contribute to this fear of cancer recurrence.81 Anxiety and depressive symptoms were associated with reduced mental health–related QOL in long-term survivors of iNHL.82 Healthcare providers should reprioritize intervention guidelines and survivorship care planning to promote HRQOL among NHL survivors, particularly in the first 6 months following treatment, by reducing physical and psychological symptom distress, addressing unmet needs, and enhancing adaptation outcomes.83
An NHL diagnosis affects not only a patient’s physical but also mental health. In a study of patients with hematological malignancies, surveys showed both the disease itself and the applied anticancer therapy may lead to adverse effects that directly affect the patient’s physical and mental health, indirectly influencing their social and professional situation.68 Mental health complications are frequent among patients with NHL, and routine assessment for symptoms of depression and anxiety should be considered as part of standard follow-up care.84 Lymphoma constitutes a specific risk factor for emerging depression and anxiety disorders, and screening and strategies to prevent development of these psychological diseases are warranted.85 Depression is highly prevalent, specifically in patients undergoing chemotherapy for NHL, and construction of a depressive symptomatology risk prediction model has shown good predictive power and clinical utility.
Women diagnosed with lymphoma in pregnancy are especially concerned with the welfare of their child and express an understandable fear of dying, as well as concerns about delay of diagnosis due to pregnancy and psychosocial supports.
Mental health support needs are often different depending on the demographics of the patient in question. Women diagnosed with lymphoma in pregnancy are especially concerned with the welfare of their child and express an understandable fear of dying, as well as concerns about delay of diagnosis due to pregnancy and psychosocial supports.58 Access to mental health support remains a challenge, with fewer than half of distressed patients in one study taking advantage of mental health services. Patients younger than 65 years are more likely to access mental health services while older patients were not, even when distressed, indicating a need for age-based approaches to outreach.86 Somewhat counterintuitively, patients with PCNSL anticipated significantly fewer negative events for their distant future compared with healthy controls and also reported fewer negative events regarding their recent past. Clinicians should be aware of these possible cognitive and affective processes and of chronic psychological disturbances in cancer survivors.87
The patient’s transition from active treatment into survivorship presents its own mental health challenges. Analysis of data from NHL survivors indicates that physical symptom distress, anxiety, depression, unmet supportive care needs, poor adaptation, and receiving chemotherapy all reduce HRQOL.83 Older women who have survived hematological cancers reported sadness, pain, distress, higher prior symptom count, and loneliness. Significant factors correlated with concerns included fatigue/sleep issues, sadness/depression, distress, higher prior symptom count, greater loneliness, and worse physical functioning.80 Anxiety and depressive symptoms were associated with reduced mental HRQOL, highlighting the need for awareness and long-term follow-up in lymphoma survivors.82 Patient-centered communication partially mediates the relationship between social support and mental health outcomes among NHL survivors; future research should focus on testing interventions that target patient-centered communication and identifying additional connections between social support and mental health outcomes.88
As with all serious health issues, NHL places significant financial burdens on many patients and their families, not only through the cost of care itself but also in wages and time lost to treatment and recovery. Treatment costs and quality vary significantly due to type of treatment and geographic location. One in 4 older adults with cancer received low-value care in the 12 months after a cancer diagnosis, and individuals who received low-value care had significantly higher out-of-pocket expenditure.89 Older patients with NHL also experience higher utilization and higher spending per utilization compared with noncancer cohorts over 5 years from cancer diagnosis. This higher utilization and spending for nonmalignant conditions provide quantifiable evidence for survivor- adapted healthcare management policies.90 Individualized DLBCL treatment in patients who require more than 2 lines of treatment is costly and results in a significant variability in resource consumption. The number of documented deaths and length of hospitalization in these cases signal a high economic burden on patients and families.91 Using an efficiency frontier approach, the most cost-effective interventions (based on cost-effectiveness ratios) in the indication of R/R DLBCL have been identified and now guide international reimbursement decisions.92 In one Canadian study, salvage chemotherapy for R/R aggressive NHL was associated with substantial indirect costs to the patients and their caregivers, with a large majority of patients not able to work or having to reduce their workload during periods of treatment. Beyond the clinical aspects of treatment costs, there is a strong association of nonbiological economic factors with NHL survival; adolescents and young adults with NHL who reside in lower-income counties are at increased risk of death, and better access and quality of care could improve the survival of lymphoma patients in the United States.11 The reality is that economic constraints influence healthcare, and cost and resource use must be considered by healthcare professionals in their ongoing efforts to design person- centered healthcare pathways.93
Long-term, patients with NHL may face a host of ongoing physical challenges. In survivors of adolescent and young adult lymphoma, hypothyroidism was the most prevalent late effect followed by secondary malignancy, pulmonary toxicity, esophageal complications, dental decay, cardiac disease, and infertility.94 Patients with NHL are at risk of long-term treatment-related bone effects, and both substantial vertebral bone loss and high incidence of fracture have been documented during survivorship.95 Fertility is often a challenge as survivors age, and low levels of anti-Müllerian hormone can result from NHL treatment and may persist for 12 months or more following completion of therapy.96 Childbirth rates for NHL survivors reach those of comparators for all NHL subtypes after 3 years. However, the cumulative incidence of childbirth was decreased throughout the 10-year follow-up for aggressive NHL.97
Long-term outcomes vary substantially depending on the cancer subtype. Newer measures of “average life span shortened” show favorable trends in premature mortality for all types of hematological cancers among the sexes.
Long-term outcomes can vary substantially depending on the cancer subtype. Newer measures of “average life span shortened” show favorable trends in premature mortality for all types of hematological cancers among the sexes. Patients with hematological cancers experienced prolonged survival over a 35-year period, although the magnitude of these life span gains varied by type of hematological cancer.98 Involvement of the CNS is a rare complication of MCL that leaves patients with limited treatment options; this form of MCL generally has dismal outcomes as evidenced by a short median overall and progression-free survival after CNS involvement.99 Differences in treatment outcomes between NHL subtypes have been observed, reflecting variations in NHL management strategies and barriers to treatment access in specific regions (in this case, Latin America). These data provide the necessary evidence to understand NHL management within this region and highlight the need to improve treatment outcomes for these patients.100
Prompt treatment appears to be key to patient success, as initiating chemotherapy within 14 days of biopsy and the use of rituximab were independently associated with improved overall and progression-free survival in patients with PCNSL.101 Emerging evidence suggests an increased incidence of late-onset complications with bendamustine-based regimens compared with CHOP/CVP, and many patients receiving treatment do not show lymphocyte recovery even 3 years following administration. Ongoing infection prophylaxis for patients receiving bendamustine-based regimens may offset translation of these findings to late-onset infectious risk.102 In patients who receive ICIs to treat NHL, the incidence of immune-related AEs was actually associated with better long-term survival. However, patients’ disease conditions must be carefully evaluated to determine optimal management.36 CAR T is effective for patients with R/R B-cell NHL, and the adverse reactions are generally controllable. Patients who see complete response after CAR T or survive for 1 year after therapy may have better long-term survival.25
Despite good functional recovery, NHL survivors often report ongoing residual impairment and cognitive issues requiring long-term rehabilitation-inclusive management.103 Up to one-third of patients with iNHL experience long-term persistent symptoms (fatigue, neuropathy, role-functioning impairment) that do not improve over time. Fatigue is a particularly pernicious long-term AE, with 1 in 3 NHL survivors experiencing clinically meaningful fatigue long after their diagnosis and initial treatment. This fatigue worsens or persists throughout survivorship for many individuals.104 Early recognition and vigilant assessment of symptoms will help provide tailored supportive care for those in need.105 Issues with cognition are a common concern for patients in survivorship, with self-perceived impaired cognitive functioning prevalent, especially among NHL survivors younger than 50 years. Therapeutic approaches targeting cognitive problems, including attention for co-occurring symptoms such as fatigue and emotional impairments, are needed to improve care for these patients.106
Patients with NHL must be appropriately educated on their reproductive options and offered ways to preserve fertility prior to treatment. A study to describe and quantify the incidence of treatment-induced late effects in adolescent and young adult lymphoma patients showed the cumulative incidence of infertility was 6.5 ± 1.6% at 5 years and 9.4 ± 2.1% at 10 years, making patient education regarding late fertility effects critical.94 Owing to the increased survival of patients with NHL of reproductive age, sperm cryopreservation and education on the testicular toxicity of treatment options must be offered to patients before commencing any treatment.107 Low serum anti- Müllerian hormone may persist months or years after completion of chemotherapy, leading to persistent menstrual abnormalities and fertility issues.96 Children of patients with NHL were more likely to be born through assisted reproductive technology than those of comparators, and fertility counseling is particularly important for patients with aggressive NHL.97
Keep up to date with the latest news from us via social networks:
To sign up for our print publication or e-newsletter, please enter your contact information below.
