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With increasing focus on novel targeted therapies for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), this longitudinal claims-based study evaluated real-world CLL/SLL treatment sequences, particularly sequential targeted therapy. Among patients with first-line (1 L) treatment in 2014-2017 (N = 2,612; median follow-up = 3 years), the most common 1 L treatment was chemoimmunotherapy (CIT; 44.6%), followed by CD20 (25.2%) and Bruton's tyrosine kinase inhibitors (BTKi; 21.7%). Among those with 1 L in 2018-2021 (N = 4,534; median follow-up = 1 year), these were BTKi (45.5%), CD20 (20.4%), CIT (17.5%), and B-cell lymphoma 2 inhibitor (8.3%). In 2014-2017, the proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 11.2% (80.2% was BTKi→BTKi); in 2018-2021, this proportion was 34.3% (66.4% was BTKi→BTKi). Over time, there was a substantial increase in targeted therapy use in 1 L and sequential targeted therapy, particularly with BTKi→BTKi. Future studies should assess clinical outcomes to determine optimal sequences for CLL/SLL and reasons for restarting BTKi. [ABSTRACT FROM AUTHOR]

Background: The first‐generation BTK inhibitor ibrutinib is a standard‐of‐care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation. Methods: This study used 2013–2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL. Results: The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow‐up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient‐months for all discontinuers and 32.9 per 1000 patient‐months for non‐discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient‐months compared with non‐discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6). Conclusion: In this first real‐world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib‐related AEs and/or new treatments to improve real‐world outcomes in patients with CLL. [ABSTRACT FROM AUTHOR]

The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton’s tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015–2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p<.001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p<.001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults. [ABSTRACT FROM AUTHOR]

Prior studies evaluating ibrutinib discontinuation are limited to clinical trials and selected medical centers and hence may not reflect real-world practice. This study used Medicare claims (2013–2019) to examine ibrutinib discontinuation and associated factors among elderly patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Over a median follow-up of 2.1years, two-thirds (65.2%) of the 11,870 new ibrutinib initiators were discontinued, with half (45.1%) of patients discontinuing within 12months of initiation. Factors such as advanced age, lack of Part D low-income subsidy, evidence of prior CLL/SLL treatment, and cardiovascular comorbidities (e.g. atrial fibrillation) were associated with higher risk of discontinuation. Over a median of 1.2years from discontinuation, 40% of discontinuers initiated another CLL/SLL treatment after ibrutinib discontinuation; 25% of patients restarted ibrutinib treatment at some point over follow-up. Our findings point to a large unmet need with the widely used BTKi ibrutinib and underscore the importance of ongoing development of efficacious and well-tolerated CLL/SLL therapies. [ABSTRACT FROM AUTHOR]

The present study assessed changes in patient management, economic burden, and overall survival (OS) in a contemporary cohort of 2775 US Medicare Advantage beneficiaries aged ≥66 years newly diagnosed with acute myeloid leukemia (AML) between 01 January 2015 and 30 June 2020. Use of venetoclax-based therapy increased and replaced hypomethylating agent (HMA) monotherapy as the most common first-line treatment choice in 2019–2020. In newly diagnosed AML patients aged ≥75 and 66–74 years, mean per-patient 1-year healthcare expenditures were $81,818 and $156,033 (2020 USD) and median OS was 2.3 and 8.5 months, respectively. In addition, 40% of Medicare Advantage patients with newly diagnosed AML continue to receive supportive care alone. These findings indicate that at the population level clinical outcomes remain poor for older adults with AML, pointing to a continuing unmet medical need. [ABSTRACT FROM AUTHOR]

Background: Although provider-level volume is frequently associated with outcomes in cancers requiring complex surgeries, whether similar relations exist for cancers treated primarily with systemic therapy is unknown.Methods: Using a population-based cohort analysis of older adults diagnosed with diffuse large B cell lymphoma (DLBCL) during the years 2004-2011, we evaluated the association between oncologist volume and 4 clinical outcomes (receipt of any chemotherapy, receipt of an anthracycline-containing or equivalent regimen, early hospitalization, and overall survival). Our primary explanatory variable was lymphoma treatment volume, defined as the number of patients with newly diagnosed lymphoma for which an oncologist initiated therapy during a 12-month look-back period from each incident DLBCL case.Results: We identified 8247 Medicare beneficiaries who were newly diagnosed with DLBCL. Chemotherapy was administered to 6202 (75.2%) beneficiaries, and 71.4% of cytotoxic regimens contained an anthracycline. Beneficiaries who were treated by higher-volume oncologists had increased odds of receiving chemotherapy (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.24-1.70; P <.001) and of receiving an anthracycline-containing regimen (aOR, 1.26; 95% CI, 1.06-1.50; P = .009). Receiving care from a higher-volume provider was also associated with decreased hospitalization (aOR, 0.80; 95% CI, 0.69-0.95; P = .007) and improved survival (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92; P < .001).Conclusion: In older adults diagnosed with DLBCL, receiving care from a provider with more experience treating lymphoma patients was associated with receipt of guideline-adherent therapy, reduced hospitalizations, and improved survival. Clinical volume may be an important factor in providing high-quality cancer care in the modern era. [ABSTRACT FROM AUTHOR]

Objectives Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The clinicopathologic features have not been well studied, and optimal management strategies remain unclear. Methods The pathology database was searched for primary gastric MALT lymphomas diagnosed from 2000 to 2017. The clinical data and the slides were reviewed. The cases were divided for analysis into those with a background of chronic gastritis with HP, chronic gastritis without HP, and without either a background of chronic gastritis or HP. Results Of 70 gastric MALT lymphoma cases identified, 26 (37% of total) had chronic gastritis and were positive for HP histologically (n = 23) or were HP positive by additional laboratory testing (n = 3). The remaining 44 (63% of total) cases were HP negative by histology. Within the HP-negative cases, 5 (11% of HP-negative cases) showed histologic gastritis while 39 (89% of HP-negative cases) did not have sufficient evidence of gastritis through review of slides (n = 18) or based on available pathology reports (n = 21). The HP-negative cases without gastritis had higher propensities to show a mass lesion on endoscopy compared with HP-positive cases (37.5% vs 11.1%, P =.02) at the initial diagnosis. The immunophenotype and rate of positive B-cell gene rearrangement were not significantly different between the 2 groups. While all HP-positive patients received antibiotics for HP eradication, treatment in the HP-negative group varied among antibiotics, radiation, rituximab, or chemotherapy. Among HP-negative patients with available follow-up, 13 (39%) showed disease recurrence, similar to the recurrence rate in HP-positive patients; however, no individual from either group has died of the disease thus far. Conclusions The incidence of HP-negative MALT lymphoma is increasing, and in our practice, it is currently more common than HP-associated MALT lymphomas. The pathophysiology of HP-negative MALT lymphoma without chronic gastritis remains unclear. Follow-up data in our study suggest that the prognosis of these cases is excellent despite varied management modalities. [ABSTRACT FROM AUTHOR]

[18F]-fluorodeoxyglucose positron emission tomography–computed tomography (PET/CT) is part of standard pretreatment staging and post-treatment assessment in patients undergoing first-line therapy for diffuse large B-cell lymphoma (DLBCL). While many providers obtain interim PET/CT (I-PET) for DLBCL, the clinical utility of these scans is unclear. We conducted a retrospective study of patients with DLBCL undergoing I-PET during first-line therapy (n= 94). The majority (61%) of patients had at least one negative I-PET and all patients with negative I-PET remained in remission at the end of treatment. I-PET was strongly associated with progression-free survival and remained independent on multivariable modeling (non-complete remission [CR]:CR I-PET, hazard ratio 2.7,p= 0.01). All patients with negative I-PET were in remission at the end of frontline therapy, and end-of-treatment PET/CT offered little clinical utility in this subset. Therefore, I-PET may offer an approach of early clinical predication and obviate the need for end-of-treatment imaging in the majority of patients with DLBCL. [ABSTRACT FROM PUBLISHER]

The diagnosis of non-Hodgkin lymphoma (NHL) is increasingly common among the elderly and it is well recognized that this patient population may benefit from therapy. No guidelines exist for chemotherapy dosing in the elderly population, and a clear assessment of treatment toxicity and benefits has not been previously reported. In this single-institution study, we report the toxicities and treatment outcomes of septuagenarians and octogenarians with large cell lymphoma treated with chemo-immunotherapy with or without radiation, as primary therapy with curative intent. We identified 37 patients over the age of 70 years diagnosed with large cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) and compared their experience with 65 patients aged less than 70 years. Our retrospective analysis suggests that elderly patients are more susceptible to treatment-related toxicity despite more frequent chemotherapy dose reductions and greater utilization of supportive care. While our aged patients experienced greater frequency of hospitalization during R-CHOP treatment, the vast majority were able to receive relative chemotherapy dose-intensity greater than 70% and experienced similar rates of complete remission. [ABSTRACT FROM AUTHOR]

AbstractThe FLT3 inhibitor quizartinib has been shown to improve overall survival when added to intensive induction chemotherapy (“7 + 3”) in patients 18-75 years old with newly diagnosed AML harboring a FLT3-ITD mutation. However, the health economic implications of this approval are unknown. We evaluated the cost-effectiveness of quizartinib using a partitioned survival analysis model. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, the addition of quizartinib to 7 + 3 resulted in incremental costs of $289,932 compared with 7 + 3 alone. With an incremental gain of 0.84 quality-adjusted life years (QALYs) with quizartinib + 7 + 3 induction vs. 7 + 3 alone, the incremental cost-effectiveness ratio for the addition of quizartinib to standard 7 + 3 was $344,039/QALY. Only an 87% reduction in the average wholesale price of quizartinib or omitting quizartinib continuation therapy after completion of consolidation therapy and allogeneic hematopoietic cell transplant would make quizartinib a cost-effective option. [ABSTRACT FROM AUTHOR]

An older patient with stage II bladder carcinoma presented with 1 week of fatigue and 2 days of dyspnea on exertion. He was receiving carboplatin/gemcitabine with 6 mg of pegylated G-CSF chemotherapy; his white blood cell count was elevated, hemoglobin low, and ferritin notably increased. What is the diagnosis and what would you do next? [ABSTRACT FROM AUTHOR]

Studies evaluating real-world outcomes and health care utilization for mantle cell lymphoma are limited. We utilized national Medicare claims (2009–2019) to examine treatment patterns, healthcare resource utilization, costs, and survival in 3664 elderly patients receiving 1 L treatment for MCL. Over a median follow-up of 2.8 years, 40.3% received at least 2 L treatment. The most common 1 L regimen was bendamustine-rituximab (50.1%), with increased use of BTKi-based regimens observed in 2 L (39.4%). Half (51.8%) of patients had an all-cause hospitalization within 12 months of initiating 1 L; hospitalization rates were higher in later lines. Healthcare costs were substantial and most costs (>80%) were MCL-related. Overall survival was poorer among later lines of treatment (median OS from initiation of 1 L: 53.5 months; 2 L: 22.0 months; 3 L: 11.8 months; 4 L: 7.8 months). These results suggest a large unmet need and future work should evaluate whether novel therapies have improved outcomes among elderly patients with MCL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the prevalence of functional and cognitive impairments, and associations between impairments and treatment among older patients with diffuse large B cell lymphoma (DLBCL) receiving nursing home (NH) care. Methods: We used the Surveillance, Epidemiology, and End Results‐Medicare database to identify beneficiaries diagnosed with DLBCL 2011–2015 who received care in a NH within −120 ~ +30 days of diagnosis. Multivariable logistic regression was used to compare receipt of chemoimmunotherapy (including multi‐agent, anthracycline‐containing regimens), 30‐day mortality, and hospitalization between NH and community‐dwelling patients, estimating odds ratios (OR) and 95% confidence interval (CI). We also examined overall survival (OS). Among NH patients, we examined receipt of chemoimmunotherapy based on functional and cognitive impairment. Results: Of the eligible 649 NH patients (median age: 82 years), 45% received chemoimmunotherapy; among the recipients, 47% received multi‐agent, anthracycline‐containing regimens. Compared with community‐dwelling patients, those in a NH were less likely to receive chemoimmunotherapy (OR: 0.34, 95%CI: 0.29–0.41), had higher 30‐day mortality (OR: 2.00, 95%CI: 1.43–2.78) and hospitalization (OR: 1.51, 95%CI: 1.18–1.93), and poorer OS (hazard ratio: 1.36, 95%CI: 1.11–1.65). NH patients with severe functional (61%) or any cognitive impairment (48%) were less likely to receive chemoimmunotherapy. Conclusions: High rates of functional and cognitive impairment and low rates of chemoimmunotherapy were observed among NH residents diagnosed with DLBCL. Further research is needed to better understand the potential role of novel and alternative treatment strategies and patient preferences for treatment to optimize clinical care and outcomes in this high‐risk population. [ABSTRACT FROM AUTHOR]

Summary: Primary mediastinal (thymic) large B‐cell lymphoma (PMBCL) is an uncommon subtype of non‐Hodgkin lymphoma (NHL) that presents with a mediastinal mass and has unique clinicopathological features. Historically, patients with PMBCL were treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy ± involved field radiation. Since a phase II trial, published in April 2013, demonstrated excellent results using dose‐adjusted (DA) R‐EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), this treatment has gained popularity. We performed a retrospective, multicentre analysis of patients aged ≥18 years with PMBCL since January 2011. Patients were stratified by frontline regimen, R‐CHOP versus DA‐R‐EPOCH. 132 patients were identified from 11 contributing centres (56 R‐CHOP and 76 DA‐R‐EPOCH). The primary outcome was overall survival. Secondary outcomes included progression‐free survival, complete response (CR) rate, and rates of treatment‐related complications. Demographic characteristics were similar in both groups. DA‐R‐EPOCH use increased after April 2013 (79% vs. 45%, P < 0·001), and there was less radiation use after DA‐R‐EPOCH (13% vs. 59%, P < 0·001). While CR rates were higher with DA‐R‐EPOCH (84% vs. 70%, P = 0·046), these patients were more likely to experience treatment‐related toxicities. At 2 years, 89% of R‐CHOP patients and 91% of DA‐R‐EPOCH patients were alive. To our knowledge, this represents the largest series comparing outcomes of R‐CHOP to DA‐R‐EPOCH for PMBCL. [ABSTRACT FROM AUTHOR]

Ivosidenib + azacitidine (IVO/AZA) is approved in the United States for newly diagnosed, older or intensive chemotherapy-ineligible patients with IDH1-mutated acute myeloid leukemia. We created a partitioned survival analysis model to evaluate the health economic implications of this approval. Model outputs were used to calculate the incremental cost-effectiveness ratio (ICER) of IVO/AZA versus AZA. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, IVO/AZA and AZA resulted in life-time costs of $403,062 and $161,887, respectively. With an incremental gain of 0.95 QALYs, the ICER of IVO/AZA was $252,782/QALY. In sensitivity analyses, only a reduction in the price of IVO by 59.3% lowered the ICER to below $150,000/QALY and 99.95% of model calculations yielded ICERs of >$150,000/QALY. In a model in which all patients received IVO monotherapy after progression on AZA monotherapy, the ICER was $155,453/QALY and various model inputs that would make IVO/AZA cost-effective were identified. [ABSTRACT FROM AUTHOR]

The BOSTON trial showed that use of once-weekly selinexor, bortezomib, and dexamethasone (SVd) prolonged progression-free survival compared to twice-weekly bortezomib and dexamethasone (Vd) in patients with relapsed or refractory (R/R) multiple myeloma (MM). In this study, we constructed a Markov model to assess the cost-effectiveness of SVd versus Vd in R/R MM. We calculated the incremental cost-effectiveness ratio (ICER) of each treatment strategy from a US payer perspective, using a lifetime horizon and a willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY). Use of SVd was associated with an incremental cost of $170,002 compared to Vd alone ($1,015,120 vs. $845,118, respectively), an incremental effectiveness of 0.35 QALYs (3.43 vs. 3.08 QALYs, respectively), and an ICER of $487,361/QALY. These data suggest that use of once-weekly SVd for R/R M/M is unlikely to be cost-effective compared to twice-weekly Vd. [ABSTRACT FROM AUTHOR]

Existing studies regarding the role of DNA methyltransferase inhibitors (DNMTi) and lenalidomide in refractory anemia with ring sideroblasts (RARS) are limited. Using the surveillance, epidemiology, and end results-medicare database, we assembled a population-based cohort of older adults diagnosed with non-del(5q) lower-risk myelodysplastic syndromes during 2007–2015. Of 2167 patients, 30% had RARS. About 16% of RARS and non- ring sideroblasts (RS) patients received DNMTi. RARS patients were more likely to receive lenalidomide (11.1% vs. 7.1%, p < 0.01). Among patients who were transfusion-dependent at treatment initiation, 55.6% of those treated with DNMTi only and 42.5% treated with lenalidomide only achieved red blood cell transfusion independence (RBC-TI) for a median duration of 21 and 12 weeks, respectively. RS status did not impact rate of RBC-TI. RARS patients had a significantly better survival, and the median survival of RARS patients varied by treatment group. In this population-based study of older RARS patients, DNMTi and lenalidomide were clinically active. [ABSTRACT FROM AUTHOR]

Medically underserved areas (MUA) or health professional shortage areas (HPSA) designations are based on primary care health services availability. These designations are used in recruiting international medical graduates (IMGs) trained in primary care or subspecialty (e.g., oncology) to areas of need. Whether the MUA/HPSA designation correlates with Oncologist Density (OD) and supports IMG oncologists' recruitment to areas of need is unknown. We evaluated the concordance of OD with the designation of MUAs/HPSAs and evaluated the impact of OD and MUA/HPSA status on overall survival. We conducted a retrospective cohort study of patients diagnosed with hematological malignancies or metastatic solid tumors in 2011 from the Surveillance Epidemiology and End Results (SEER) database. SEER was linked to the American Medical Association Masterfile to calculate OD, defined as the number of oncologists per 100,000 population at the county level. We calculated the proportion of counties with MUA or HPSA designation for each OD category. Overall survival was estimated using the Kaplan-Meier method and compared between the OD category using a log-rank test. We identified 68,699 adult patients with hematologic malignancies or metastatic solid cancers in 609 counties. The proportion of MUA/HPSA designation was similar across counties categorized by OD (93.2%, 95.4%, 90.3%, and 91.7% in counties with <2.9, 2.9–6.5, 6.5–8.4 and >8.4 oncologists per 100K population, p = 0.7). Patients' median survival in counties with the lowest OD was significantly lower compared to counties with the highest OD (8 vs. 11 months, p<0.0001). The difference remained statistically significant in multivariate and subgroup analysis. MUA/HPSA status was not associated with survival (HR 1.03, 95%CI 0.97–1.09, p = 0.3). MUA/HPSA designation based on primary care services is not concordant with OD. Patients in counties with lower OD correlated with inferior survival. Federal programs designed to recruit physicians in high-need areas should consider the availability of health care services beyond primary care. [ABSTRACT FROM AUTHOR]

Context: Patients with blood cancers have low rates of timely hospice use. Barriers to hospice use for this population are not well understood. Lack of transfusion access in most hospice settings is posited as a potential reason for low and late enrollment rates.Objectives: We explored the perspectives of patients with blood cancers and their bereaved caregivers regarding the value of hospice services and transfusions.Methods: Between June 2018 and January 2019, we conducted three focus groups with blood cancer patients with an estimated life expectancy of six months or less and two focus groups with bereaved caregivers of patients with blood cancers. We asked participants their perspectives regarding quality of life (QOL) and about the potential association of traditional hospice services and transfusions with QOL. A hematologic oncologist, sociologist, and qualitatively trained research assistant conducted thematic analysis of the data.Results: Twenty-seven individuals (18 patients and nine bereaved caregivers) participated in the five focus groups. Participants identified various QOL domains that were important to them but focused largely on a desire for energy to maintain physical/functional well-being. Participants considered transfusions a high-priority service for their QOL. They also felt that standard hospice services were important for QOL. Bereaved caregivers reported overall positive experiences with hospice.Conclusion: Our analysis suggests that although patients with blood cancers value hospice services, they also consider transfusions vital to their QOL. Innovative care delivery models that combine the elements of standard hospice services with other patient-valued services like transfusions are most likely to optimize end-of-life care for patients with blood cancers. [ABSTRACT FROM AUTHOR]

Hypomethylating agents (HMA) showed overall survival (OS) benefits in patients with higher-risk myelodysplastic syndromes (HR-MDS) in clinical trials. We conducted a retrospective cohort study of Surveillance, Epidemiology, and End Results (SEER)-Medicare data of patients ≥66 years diagnosed with refractory anemia with excess blasts (RAEB), a proxy for HR-MDS, in 01/2001–04/2004 (pre-period) or 01/2006–12/2011 (post-period). Association between post-period diagnosis and OS was examined using propensity scores (PS)-matched samples. Among 1876 RAEB patients, median OS was 9 months and 30.8% received HMAs (3.6% in pre-period; 43.0% in post-period) with no association between post-period diagnosis and OS. In the top PS quartile, post-period diagnosis was associated with a 74% lower risk of death (Hazard ratio [HR] = 0.26, 95%-CI: 0.10–0.69, p = 0.007), while outcomes were worse in the lowest PS quartile (HR = 2.80, 95%-CI: 1.06–7.36, p = 0.037). HMA lead to a 3-month OS benefit for patients most likely to receive HMA but not for unselected RAEB cohort. [ABSTRACT FROM AUTHOR]

Population level survival of patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) is inferior to clinical trials. Using SEER-Medicare data, we identified 2086 MDS patients diagnosed in 2004–13, aged ≥66 years at diagnosis, and receiving ≥1 HMA cycle after 2005. We used multivariate logistic regression and Cox proportional hazards models to assess the impact of provider experience on persistent HMA therapy and overall survival (OS), respectively. Median number of HMA cycles was 4 and median OS was 10 months. Thirty-two percent of patients were treated by providers with ≥1 prior HMA initiation in the last 2 years and were more likely to receive ≥4 cycles of HMA therapy (OR = 1.29, 95% CI = 1.06–1.57; p =.01). No significant association was found between MDS or HMA initiation volume and survival. In conclusion, while HMA initiation volume was associated with persistent HMA treatment, neither MDS nor HMA initiation volumes were associated with OS in older MDS patients. [ABSTRACT FROM AUTHOR]

Most patients with lower risk myelodysplastic syndromes (LR-MDS) become red blood cell (RBC) transfusion dependent at some time during their disease course. Hypomethylating agents (HMAs) are frequently used in this setting; however, reported rates of in RBC transfusion independence (TI) achieved with HMA therapy vary significantly between studies. Here we study the real-life clinical effectiveness of HMA in inducing RBC TI in anemic LR-MDS patients using the Surveillance, Epidemiology and End Results (SEER)-Medicare database. We find that approximately 40% of LR-MDS patients who were receiving RBC transfusions and 33% who were dependent on RBC transfusions at HMA initiation ultimately achieved TI. The receipt of ≥3 transfusions in the 8-week period before HMA initiation was significantly associated with lower odds of achieving TI. Our study provides important population level estimates of clinical effectiveness of HMAs in LR-MDS. [ABSTRACT FROM AUTHOR]

Background: The majority of patients with acute myeloid leukemia (AML) are aged >65 years at the time of diagnosis and are not actively treated. The objective of the current study was to determine the prevalence, temporal trends, and factors associated with no active treatment (NAT) among older patients with AML in the United States.Methods: A retrospective analysis was performed of Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 14,089 patients with AML residing in the United States who were diagnosed with AML at age ≥66 years during 2001 through 2013. NAT was defined as not receiving any chemotherapy, including hypomethylating agents. Multivariable logistic regression models were used to analyze sociodemographic, clinical, and provider characteristics associated with NAT.Results: The percentage of patients with NAT decreased over time from 59.7% among patients diagnosed in 2001 to 42.8% among those diagnosed in 2013. The median overall survival for the entire cohort was 82 days from the time of diagnosis. Patients treated with NAT had worse survival compared with those receiving active treatment. Variables found to be associated with higher odds of NAT included older age, certain sociodemographic characteristics (household income within the lowest quartile, residence outside the Northeast region of the United States, and being unmarried), and clinical factors (≥3 comorbidities, the presence of mental disorders, recent hospitalization, and disability).Conclusions: Greater than one-half of older patients with AML residing in the United States do not receive any active leukemia-directed therapy despite the availability of lower intensity therapies such as hypomethylating agents. Lack of active therapy receipt is associated with inferior survival. Identifying predictors of NAT might improve the quality of care and survival in this patient population, especially as novel therapeutic options with lower toxicity are becoming available. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Despite the approval of azacitidine in 2004 and the approval of decitabine in 2006 in the United States for chronic myelomonocytic leukemia (CMML), the overall survival (OS) benefit with hypomethylating agent (HMA) therapy is unclear.Methods: Older adults (age ≥ 66 years) who had been diagnosed with CMML from 2001 to 2011 were selected from the Surveillance, Epidemiology, and End Results-Medicare database, and propensity score matching was used to match patients who had been diagnosed after HMA approval (2007-2011) and had received HMA treatment with patients diagnosed before HMA approval (2001-2003). Cox proportional hazards models with the matched sample were used to assess the change in OS. A second matched cohort of patients who did not receive HMA after approval and patients diagnosed before HMA approval was used to evaluate survival change attributable to other potential differences between the 2 time periods, such as improved supportive care.Results: Among 1378 older adults diagnosed with CMML, the median OS was 13 months, and 18.8% received HMAs. In the primary matched analysis, with 225 HMA users diagnosed in 2007-2011 and 395 patients diagnosed in 2001-2003, the median OS times were 17 and 11 months, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.58-0.91; P = .005). In a secondary analysis, the risk of death did not differ between 395 propensity score-matched HMA nonusers diagnosed in 2007-2011 and 484 patients diagnosed in 2001-2003 (hazard ratio, 1.09; 95% CI, 0.91-1.32; P = .34).Conclusions: Despite limited evidence, HMAs are commonly used to treat older CMML patients. The use of HMAs was associated with a 28% reduction in the risk of death in adjusted analyses. Improvements in supportive care do not appear to account for temporal improvements in OS. Cancer 2017;123:3754-3762. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: In a recent randomized, placebo-controlled trial, consolidation treatment with brentuximab vedotin (BV) decreased the risk of Hodgkin lymphoma (HL) progression after autologous stem cell transplantation (ASCT). However, the impact of BV consolidation on overall survival, quality of life, and health care costs remain unclear.Methods: A Markov decision-analytic model was constructed to measure the costs and clinical outcomes for BV consolidation therapy compared with active surveillance in a cohort of patients aged 33 years who were at risk for HL relapse after ASCT. Life-time costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each post-ASCT strategy.Results: After quality-of-life adjustments and standard discounting, upfront BV consolidation was associated with an improvement of 1.07 QALYs compared with active surveillance plus BV as salvage. However, the strategy of BV consolidation led to significantly higher health care costs ($378,832 vs $219,761), resulting in an ICER for BV consolidation compared with active surveillance of $148,664/QALY. If indication-specific pricing was implemented, then the model-estimated BV price reductions of 18% to 38% for the consolidative setting would translate into ICERs of $100,000 and $50,000 per QALY, respectively. These findings were consistent on 1-way and probabilistic sensitivity analyses.Conclusions: BV as consolidation therapy under current US pricing is unlikely to be cost effective at a willingness-to-pay threshold of $100,000 per QALY. However, indication-specific price reductions for the consolidative setting could reduce ICERs to widely acceptable values. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3763-3771. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: There are inconsistent and limited data regarding the risk of myeloid neoplasms (MN) among breast cancer survivors who received radiotherapy (RT) in the absence of chemotherapy. Concern about subsequent MN might influence the decision to use adjuvant RT for women with localized disease. As patients with therapy-related MN have generally poor outcomes, the presumption of subsequent MN being therapy-related could affect treatment recommendations. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to study older women with in-situ or stage 1–3 breast cancer diagnosed 2001–2009 who received surgery. Chemotherapy and RT were ascertained using Medicare claims, and new MN diagnoses were captured using both SEER registry and Medicare claims. We excluded women who received chemotherapy for initial treatment, and censored at receipt of subsequent chemotherapy. Competing-risk survival analysis was used to assess the association between RT and risk of subsequent MN adjusting for relevant characteristics. Results: Median follow-up for 60,426 eligible patients was 68 months (interquartile range, 46 to 92 months), with 47.6% receiving RT. In total, 316 patients (0.52%) were diagnosed with MN; the cumulative incidence per 10,000 person-years was 10.6 vs 9.0 among RT-treated vs non-RT-treated women, respectively (p = .004); the increased risk of subsequent MN persisted in the adjusted analysis (hazard ratio = 1.36, 95% confidence interval: 1.03–1.80). The results were consistent in multiple sensitivity analyses. Conclusions: Our data suggest that RT is associated with a significant risk of subsequent MN among older breast cancer survivors, though the absolute risk increase is very small. These findings suggest the benefits of RT outweigh the risks of development of subsequent MN. [ABSTRACT FROM AUTHOR]

The article presents research on the improvement in the survival of a refractory anemia patient having excess blasts in the U.S. Topics discussed include the treatment options of myelodyslastic syndrome patients, the development of new drugs, and the significance of the improvement of the patient's overall survival.

The hypomethylating agents ( HMAs) azacitidine and decitabine are both approved for treatment of myelodysplastic syndromes ( MDS) in the USA. In Europe, decitabine is not approved due to lack of survival advantage in randomized trials. The two drugs have not been compared in clinical trials. We identified patients diagnosed with MDS between 2004 and 2011 from the Surveillance, Epidemiology, and End Results ( SEER)-Medicare linked database in the USA who received ≥ 10 doses of either HMA. We estimated survival from HMA initiation with Kaplan-Meier methods and used multivariate Cox proportional hazards models to adjust for covariates. Analyses controlled for histological subtype and we conducted a subset analysis limited to patients with refractory anaemia with excess blasts ( RAEB). In 2025 HMA-treated patients, median survival was 15 months with no difference in survival based on the HMA received in adjusted analysis (decitabine versus azacitidine, hazard ratio = 1·06, 95% confidence interval: 0·94-1·19, P = 0·37). For RAEB patients ( n = 523), median survival was 12 months, with no significant difference based on HMA received. No significant survival difference was found between azacitidine and decitabine in patients with MDS, including RAEB. Importantly, population-based survival of azacitidine-treated RAEB patients was substantially shorter than in the AZA-001 clinical trial (11 versus 24·5 months). [ABSTRACT FROM AUTHOR]

A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor ( CAR)-modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre-plasma cell or B lymphoid differentiation (including CD19) highlights the ability of such mature lymphomas to evade lineage-specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19-negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen-directed CAR-T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time. [ABSTRACT FROM AUTHOR]