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In the randomized phase III IDHENTIFY trial, the IDH2 inhibitor enasidenib (ENA) showed improvement in event-free but not overall survival compared with conventional care regimens (CCR) among patients with relapsed/refractory (R/R), IDH2 -mutant AML. We constructed a partitioned survival model to evaluate the cost-effectiveness of enasidenib for the treatment of older patients with R/R, and  IDH2 -mutant AML. In the base-case scenario, ENA exhibited an incremental effectiveness of 0.234quality-adjusted life-years (QALYs) compared to CCR, and an incremental cost of $126,800, leading to an incremental cost-effectiveness ratio of $540,300/QALY(95% CI: $197,800-$4,777,000/QALY). In probabilistic sensitivity analysis, CCR was favored in 99.8% of simulations. The cost of ENA would need to be decreased by 72% to be cost-effective at a willingness-to-pay threshold of $150,000/QALY. Our findings suggest that ENA is unlikely to be a cost-effective treatment for older patients with IDH2- mutant R/R AML under current pricing.

The 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.

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.

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 12 months 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.

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 2.1 years, two-thirds (65.2%) of the 11,870 new ibrutinib initiators were discontinued, with half (45.1%) of patients discontinuing within 12 months 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 1.2 years 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.

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.

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.

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.

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.

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.

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.

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.

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.

Introduction : The cost of acute myeloid leukemia (AML) treatment is substantial and increasing. Inpatient treatment costs for allogeneic hematopoietic stem cell transplant (HSCT) and intensive chemotherapy are the main cost drivers in AML, however this pattern may change as new, expensive oral therapies enter the market. Areas covered : The authors provide an overview of the healthcare costs in patients with AML treated with various modalities (intensive chemotherapy, allogeneic HSCT, low-intensity treatment and supportive care only). The authors review both the impact of the recently approved novel AML agents and an increasingly personalized treatment approach on healthcare resources. Finally, the authors discuss whether these treatments are cost-effective from a societal perspective and how the increase in AML-associated costs can potentially be slowed. Expert opinion : The direct healthcare costs of AML are substantial and vary depending on the treatment approach, the country studied, and in the United States, a patient's insurance status. Treatment costs have increased out of proportion to general inflation and this trend is likely going to continue or even accelerate. Societal consensus on cost-effectiveness is essential. It remains to be seen how advances in diagnostic techniques and the incorporation of novel agents will impact medical outcomes, costs and influence health policy.

[(18)F]-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.

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.