Association of iron infusion reactions with ABO blood type.

OBJECTIVES: We sought to determine risk factors for iv iron infusion-related reactions (IRR), and identify strategies for iron repletion after IRR. METHODS: We conducted a retrospective chart review of patients treated in the classical hematology clinic at Yale Cancer Center (n = 330 consecutive patients) from 2016 to 2021, who received iv ferumoxytol (60.3%), iron sucrose (14.8%), or iron dextran (10.9%). RESULTS: The iv iron IRR was noted in 58 (17.6%) patients, 62.1% of whom had previously tolerated iv iron. The severity of IRR was mild in 22, moderate in 23, and severe in 11 patients. Most (72.4%) patients who experienced IRR tolerated a subsequent iv iron infusion. On multivariable analysis, a history of non-medication allergies was associated with greater odds of IRR (odds ratio [OR] 2.12, 95% confidence interval (CI): 1.16-3.87, p = .01). No patients with type AB blood, and few with type A blood (n = 6), had IRR; compared to type A or AB together, patients with type B (OR 5.00, 95% CI: 1.56-16.06, p = .007) or type O (OR 3.71, 95% CI: 1.44-9.55, p = .007) blood had greater odds of IRR. CONCLUSIONS: This study highlights a possible association of blood type with iv iron IRR; prospective studies with larger patient numbers are warranted to explore this association.

Underutilization of guideline-recommended supportive care among older adults with multiple myeloma in the United States.

BACKGROUND: With improving survival for patients with multiple myeloma (MM), supportive care that is focused on optimizing quality of life and minimizing treatment-related toxicities is increasingly important. The extent to which patients with MM are receiving recommended supportive care is unknown. METHODS: This study used the Surveillance, Epidemiology, and End Results-Medicare database to identify older adults (age ≥66 years) diagnosed with MM in 2008-2013 who had received active treatment and survived 1 year or longer after their diagnosis. Outcomes of interest included guideline-recommended supportive care, which was defined as 1) bone-modifying drugs (BMDs) within the 12 months after the diagnosis, 2) influenza vaccination in the first season after the diagnosis, and 3) concomitant use of prophylactic antivirals with proteasome inhibitors. Multivariable logistic regression models were used to evaluate associations between patient/facility-level characteristics and supportive care use. RESULTS: Among 1996 patients receiving MM-directed therapy, 64%, 52%, and 49% received BMDs, an influenza vaccination, and antiviral prophylaxis, respectively. Non-Hispanic black patients (odds ratio [OR] vs white patients, 0.63; 95% confidence interval [CI], 0.46-0.88) and patients with baseline renal impairment (OR, 0.43; 95% CI, 0.34-0.54) had lower odds of BMDs. Non-Hispanic blacks (OR, 0.52; 95% CI, 0.37-0.73) and those with dual Medicaid enrollment (OR, 0.76; 95% CI, 0.58-0.99) had lower odds of influenza vaccination. Treatment in a community-based setting was associated with reduced odds of antiviral prophylaxis (OR, 0.58; 95% CI, 0.46-0.72). CONCLUSIONS: Substantial underutilization of guideline-recommended supportive care was observed among older adults with MM in the United States, and this was associated with both patient and facility characteristics. Targeted interventions are needed to improve supportive care for patients with MM.

Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma.

Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of α-galactosylceramide-loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase in serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans.

Malignancies associated with epstein-barr virus: pathobiology, clinical features, and evolving treatments.

Epstein-Barr virus (EBV) is associated with a wide variety of B-cell-derived lymphoid neoplasms, including Burkitt lymphoma, lymphomas arising in immunocompromised patients (post-transplant and HIV-associated lymphomas), and Hodgkin lymphoma. In addition, EBV has been linked to some T-cell lymphomas (angioimmunoblastic T-cell lymphoma, extranodal nasal-type natural killer/T-cell lymphoma, and other rare histotypes), nasopharyngeal cancer, and a subset of gastric cancers. Advances in our understanding of the pathobiology of EBV oncogenesis, including the transforming and immunogenic properties of the virus and the role of immune dysregulation, have provided the rationale for new treatment strategies. Emerging EBV-specific therapeutic approaches include activation of lytic viral infection combined with antiviral drugs, inhibition of EBV-induced oncogenic cellular signaling pathways, adoptive EBV-specific T-cell therapies, and EBV vaccines. This review summarizes the pathobiology, clinical features, and treatment of EBV-associated malignancies, including new and evolving therapies focused on exploiting the pathobiology of EBV.

Racial differences in treatment and survival among older patients with multiple myeloma.

BACKGROUND: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non-Hispanic African American (NHAA) and non-Hispanic White (NHW) patients are well-established, it is unclear whether they have persisted after the introduction of novel agents. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs). RESULTS: Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment during the first year, respectively. Discrepancy in the proportion of patients receiving treatment between the two groups increased from 2.9% in 2007 to 2009 to 6.9% in 2014-2017. After controlling for relevant factors, patients who received treatment within the first year had lower mortality than those who did not (HR = 0.90, 95% confidence interval [CI]: 0.86-0.94). NHAA patients had a lower probability to receive treatments during the first year than NHW patients (HR = 0.91, 95% CI: 0.85-0.97) but had lower mortality (HR = 0.94, 95% CI: 0.88-1.00). The lower mortality was only observed among patients who received no treatment (HR = 0.84, 95% CI: 0.77-0.93); NHAA and NHW patients who received treatment had similar survival (p = 0.63). CONCLUSIONS: The increasing racial disparity in treatment utilization over time is concerning. Efforts are needed to eliminate the barriers of receiving treatment.

Patient Perspectives on Social and Identity Factors Affecting Multiple Myeloma Care: Barriers and Opportunities.

Patients living with multiple myeloma (MM) have a substantial disease burden and face multiple barriers to care. Building upon our previous research using mixed methods, this focus group research aimed to identify patients' priorities regarding specific social and identity-related needs, map these prioritized needs to the disease journey, and describe patient-generated ideas to improve patient support. Participants noted that patients with MM need a range of emotional, social, and financial support throughout the disease journey. They identified initial MM diagnosis and treatment adherence as two critical points in the MM journey where patients need the most support and assistance. The findings of this research suggest that overall, patients with MM need comprehensive support, ideally from a multidisciplinary team consisting of health care providers, patient advocates, social workers, and psychologists to help patients understand their disease and treatment options, make informed treatment decisions, adhere to treatment, and ultimately reduce their disease burden and improve outcomes. This research revealed that patients with MM need varying types and levels of support, with the most common needs including information on disease and treatment, connections to financial resources and support systems, assistance with navigating insurance options, and transportation and logistical support for medical appointments.

Impact of Social Needs and Identity Experiences on the Burden of Illness in Patients with Multiple Myeloma: A Mixed-Methods Study.

Multiple myeloma (MM) is a common hematologic malignancy, but due to its incurable nature, patients experience many relapses in their lifetime and hence face unique challenges. This mixed-methods study consisting of an online survey and subsequent focus groups aimed to understand how social and identity experiences affected the diagnostic, treatment, and care journey for patients with MM. Twenty-three adult patients with MM participated in this study. The survey participants identified common determinants negatively impacting their health, including mental health concerns (experienced by 90.5% of respondents), worries about food shortage (42.9%), and transportation concerns (28.6%). Focus group participants described high physical and mental health burdens associated with MM. Frequent monitoring, fear of a relapse, and unpredictable side effects contributed to high anxiety. Participants indicated that MM differed from other types of cancer and chronic health conditions in many ways, particularly how and where the diagnosis was made, disease progression and relapse, treatments and side effects, and financial concerns. Most participants (65.0%) reported ≥1 social need that negatively impacted health outcomes including lack of knowledge about MM, financial instability, and lack of insurance, transportation, and social support. The findings reveal that patients with MM continually experience patient-specific mental and physical health burdens indicating high unmet needs throughout the disease journey.

Aplastic anemia in association with multiple myeloma: clinical and pathophysiological insights.

We investigated immune cytopenia in multiple myeloma (MM) patients with concurrent acquired aplastic anemia (AA), focusing on three clinical cases treated with plasma cell-directed therapy. All three patients achieved partial response in MM and one patient experienced complete resolution of AA. Two patients had partial improvement in transfusion requirement but continued to suffer from severe AA, leading to immunosuppressive therapy (IST) with improvement of transfusion requirement in both patients. In vitro serum testing of these patients demonstrated platelet mitochondrial dysfunction and platelet apoptosis but did not show sera-specific inhibition of erythroid colony formation in progenitor cells. The levels of IL8 and IL15 were elevated in MM patients with AA, implicating their potential roles in this co-occurrence. Response to IST points to the possibility of myeloma-dysregulated immune system leading to autoreactive T-cell destruction of hematopoietic stem and progenitor cells, offering insights for developing new treatment for cytopenia in MM.

Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence.

Tyrosine kinase inhibitor (TKI) use is critical in the care of patients with chronic myeloid leukemia (CML). Quantitative polymerase chain reaction (qPCR) testing for BCR-ABL1 every 3 months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1192 patients aged ≥66 years (median age, 74 years) with newly diagnosed CML who were followed up for ≥13 months from TKI initiation. In total, 965 patients (81.0%) had ≥1 test, with 425 (35.7%) and 540 (45.3%) of the patients tested during 1, 2, and ≥3 quarters (optimal monitoring) of the first year from TKI initiation, respectively. In multivariable analysis, diagnosis in later years and influenza vaccination before diagnosis, a proxy for health care access, were associated with optimal qPCR monitoring. Use of low-income subsidy and residing in census tracts with the lowest socioeconomic status were associated with less optimal monitoring. Patients with optimal monitoring were 60% more likely to be TKI adherent (odds ratio, 1.60; 95% CI, 1.11-2.31; P = .01) and had improved 5-year survival (hazard ratio, 0.66; 95% CI, 0.49-0.90; P < .01) than those without such monitoring. In this large, real-world study of CML management patterns, many older patients had suboptimal molecular monitoring, which was associated with decreased TKI adherence and worse survival.

Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM.

Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma.

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia.

BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. METHODS: We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. RESULTS: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups. CONCLUSIONS: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

The COVID-19 Pandemic and In-Person Visit Rate Disruptions Among Patients With Hematologic Neoplasms in the US in 2020 to 2021.

Importance: The COVID-19 pandemic has led to a reduction in routine in-person medical care; however, it is unknown whether there have been any changes in visit rates among patients with hematologic neoplasms. Objective: To examine associations between the COVID-19 pandemic and in-person visits and telemedicine use among patients undergoing active treatment for hematologic neoplasms. Design, Setting, and Participants: Data for this retrospective observational cohort study were obtained from a nationwide electronic health record-derived, deidentified database. Data for patients with hematologic neoplasms who had received at least 1 systemic line of therapy between March 1, 2016, and February 28, 2021, were included. Treatments were categorized into 3 types: oral therapy, outpatient infusions, and inpatient infusions. The data cutoff date was April 30, 2021, when study analyses were conducted. Main Outcomes and Measures: Monthly visit rates were calculated as the number of documented visits (telemedicine or in-person) per active patient per 30-day period. We used time-series forecasting methods on prepandemic data (March 2016 to February 2020) to estimate expected rates between March 1, 2020, and February 28, 2021 (if the pandemic had not occurred). Results: This study included data for 24 261 patients, with a median age of 68 years (IQR, 60-75 years). A total of 6737 patients received oral therapy, 15 314 received outpatient infusions, and 8316 received inpatient infusions. More than half of patients were men (14 370 [58%]) and non-Hispanic White (16 309 [66%]). Early pandemic months (March to May 2020) demonstrated a significant 21% reduction (95% prediction interval [PI], 12%-27%) in in-person visit rates averaged across oral therapy and outpatient infusions. Reductions in in-person visit rates were also significant for all treatment types for multiple myeloma (oral therapy: 29% reduction; 95% PI, 21%-36%; P = .001; outpatient infusions: 11% reduction; 95% PI, 4%-17%; P = .002; inpatient infusions: 55% reduction; 95% PI, 27%-67%; P = .005), for oral therapy for chronic lymphocytic leukemia (28% reduction; 95% PI, 12%-39%; P = .003), and for outpatient infusions for mantle cell lymphoma (38% reduction; 95% PI, 6%-54%; P = .003) and chronic lymphocytic leukemia (20% reduction; 95% PI, 6%-31%; P = .002). Telemedicine visit rates were highest for patients receiving oral therapy, with greater use in the early pandemic months and a subsequent decrease in later months. Conclusions and Relevance: In this cohort study of patients with hematologic neoplasms, documented in-person visit rates for those receiving oral therapy and outpatient infusions significantly decreased during the early pandemic months but returned to close to projected rates in the later half of 2020. There were no statistically significant reductions in the overall in-person visit rate for patients receiving inpatient infusions. There was higher telemedicine use in the early pandemic months, followed by a decline, but use was persistent in the later half of 2020. Further studies are needed to ascertain associations between the COVID-19 pandemic and subsequent cancer outcomes and the evolution of telemedicine use for care delivery.

Refractory autoimmune hemolytic anemia in a systemic lupus erythematosus patient: A clinical case report.

Warm autoimmune hemolytic anemia (AIHA) is a hematologic disorder with an incidence of 1-3 per 105 individuals/year. Patients with systemic lupus erythematosus (SLE) develop AIHA in 3% of adult cases and 14% of pediatric cases. We report a case of AIHA refractory to multiple lines of treatment in a patient with SLE, who eventually responded to a proteasome inhibitor-based combination. A patient with systemic lupus erythematous was diagnosed with symptomatic autoimmune hemolytic anemia. The patient was refractory to multiple lines of treatment including prednisone, intravenous immune globulin, methylprednisolone, rituximab, cyclophosphamide, mycophenolate mofetil, and splenectomy. She eventually had a beneficial response to a proteasome inhibitor-based combination with bortezomib plus mycophenolate mofetil. The treatment of refractory autoimmune hemolytic anemia can be challenging. Patients with AIHA refractory to primary or secondary treatments must resort to receiving novel therapeutic modalities including combinations targeting plasma cell, T- and B-cell proliferation.

Practice patterns and real-life outcomes for patients with acute promyelocytic leukemia in the United States.

Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and population-based registries vary; potential explanations include a delay in treatment and lower adherence to guideline-recommended therapy in real-world practice. We used the Vizient Clinical Data Base to describe demographic characteristics, baseline clinical characteristics, and treatment patterns in patients newly diagnosed with APL during the study period of April 2017 to March 2020. Baseline white blood cell count was used to assign risk status and assess treatment concordance with National Comprehensive Cancer Network guidelines. Logistic regression models examined adjusted associations between patient, hospital, disease characteristics, and adverse outcomes (in-hospital death or discharge to hospice). Among 1464 patients with APL, 205 (14.0%) experienced an adverse outcome. A substantial subset (20.6%) of patients did not receive guideline-concordant regimens. Odds of adverse outcomes increased with failure to receive guideline-concordant treatment (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.43-3.75; P = .001), high-risk disease (OR, 2.48; 95% CI, 1.53-4.00; P < .001), and increasing age (≥60 years: OR, 11.13; 95% CI, 4.55-27.22; P < .001). Higher hospital acute myeloid leukemia (AML) patient volume was associated with lower odds of adverse outcome (OR, 0.44; 95% CI, 0.20-0.99 [for ≤50 vs >200 AML patients per year]; P = .046). In conclusion, in this large database analysis, 14.0% of patients newly diagnosed with APL died or were discharged to hospice. A substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.

Impact of the COVID-19 Pandemic on Treatment Patterns for Patients With Metastatic Solid Cancer in the United States.

BACKGROUND: The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic's impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. METHODS: We used an electronic health record-derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. RESULTS: The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = -2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = -2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. CONCLUSIONS: Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers.

Cost-Effectiveness of First-Line Versus Second-Line Use of Daratumumab in Older, Transplant-Ineligible Patients With Multiple Myeloma.

PURPOSE: The MAIA trial found that addition of daratumumab to lenalidomide and dexamethasone (DRd) significantly prolonged progression-free survival in transplant-ineligible patients with newly diagnosed multiple myeloma, compared with lenalidomide and dexamethasone alone (Rd). However, daratumumab is a costly treatment and is administered indefinitely until disease progression. Therefore, it is unclear whether it is cost-effective to use daratumumab in the first-line setting compared with reserving its use until later lines of therapy. METHODS: We created a Markov model to compare healthcare costs and clinical outcomes of transplant-ineligible patients treated with daratumumab in the first-line setting compared with a strategy of reserving daratumumab until the second-line. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for first-line daratumumab versus second-line daratumumab from a US payer perspective. RESULTS: First-line daratumumab was associated with an improvement of 0.52 QALYs and 0.66 discounted life-years compared with second-line daratumumab. While both treatment strategies were associated with considerable lifetime expenditures ($1,434,937 v $1,112,101 in US dollars), an incremental cost of $322,836 for first-line daratumumab led to an ICER of $618,018 per QALY. The cost of daratumumab would need to be decreased by 67% for first-line daratumumab to be cost-effective at a willingness-to-pay threshold of $150,000 per QALY. CONCLUSION: Using daratumumab in the first-line setting for transplant-ineligible patients may not be cost-effective under current pricing. Delaying daratumumab until subsequent lines of therapy may be a reasonable strategy to limit healthcare costs without significantly compromising clinical outcomes. Mature overall survival data are necessary to more fully evaluate cost-effectiveness in this setting.

Impact of the COVID-19 pandemic on treatment patterns for US patients with metastatic solid cancer.

BACKGROUND: The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic's impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. METHODS: We used an electronic health record-derived longitudinal database curated via technology-enabled abstraction to identify 14,136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at ∼280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. RESULTS: The adjusted probability of treatment within 30 days of diagnosis [95% confidence interval] was similar across periods: January-March 2019 41.7% [32.2%, 51.1%]; April-July 2019 42.6% [32.4%, 52.7%]; January-March 2020 44.5% [30.4%, 58.6%]; April-July 2020 46.8% [34.6%, 59.0%]; adjusted percentage-point difference-in-differences 1.4% [-2.7%, 5.5%]. Among 5,962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences 1.6% [-2.6%, 5.8%]). There was no meaningful effect modification by cancer type, race, or age. CONCLUSIONS: Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not impact time to treatment initiation or treatment selection for patients with metastatic solid cancers.

Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents.

Chromosome 1 abnormalities (C1As) are common genetic aberrations among patients with multiple myeloma (MM). We aimed to evaluate the significance of C1As among a contemporary cohort of patients with MM in the United States. We used electronic health records from the Flatiron Health database to select patients newly diagnosed with MM from January 2011 to March 2018 who were tested using fluorescence in situ hybridization within 90 days of diagnosis. We characterized patients as having documented C1As or other high-risk chromosomal abnormalities (HRCAs) as defined by the Revised-International Staging System (R-ISS) such as del(17p), t(14;16), and t(4;14). We used Kaplan-Meier methods to compare overall survival (OS) of patients with or without C1As and stratified log-rank tests (with the presence of HRCAs as a stratifying variable). We used Cox proportional hazards regression models to compare OS, adjusting for age, sex, stage, HRCAs, and type of first-line therapy. Of 3578 eligible patients, 844 (24%) had documented C1As. Compared with patients without C1As, patients with C1As were more likely to have higher stage (R-ISS stage III; 18% vs 12%), to have HRCAs (27% vs 14%), and to receive combinations of proteasome inhibitors and immunomodulatory agents (41% vs 34%). Median OS was lower for patients with C1As (46.6 vs 70.1 months; log-rank P < .001). C1As were independently associated with worse OS (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-2.69; P < .001), as were older age, higher R-ISS stage, HRCAs, and immunoglobulin A isotype. C1As were associated with inferior OS, independent of other HRCAs, despite greater use of novel therapies. Clinical trials testing newer therapies for high-risk MM should incorporate patients with C1As.

Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States.

The hypomethylating agents (HMAs) azacitidine and decitabine have been the de facto standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive therapy. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 2263 older adults (age ≥66 years) diagnosed with AML during 2005-2015 who received a first-line HMA; 1154 (51%) received azacitidine, and 1109 (49%) received decitabine. Median survival from diagnosis was 7.1 and 8.2 months (P < .01) for azacitidine- and decitabine-treated patients, respectively. Mortality risk was higher with azacitidine vs decitabine (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.01-1.21; P = .02). The findings were similar when evaluating only patients completing ≥4 cycles (42% of patients treated with either azacitidine or decitabine). These findings lost significance when evaluating those completing a standard 7-day schedule of azacitidine (34%) vs 5-day schedule for decitabine (66%) (HR, 0.95; 95% CI, 0.83-1.08; P = .43). Red blood cell (RBC) transfusion independence (TI) was achieved in one-third of patients with no difference between the 2 HMAs. In conclusion, the majority of older AML patients did not receive the minimum of 4 cycles of HMA often needed to elicit clinical benefit. We observed no clinically meaningful differences between azacitidine- and decitabine-treated patients in their achievement of RBC TI or survival.