Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult AML patients from six urban cancer centers and revealed inferior survival among NHB (HR=1.59, 95% CI: 1.15, 2.22) and Hispanic (HR=1.25, 95% CI: 0.88, 1.79) compared to NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across six composite variables: structural racism (census tract disadvantage, affluence and segregation), tumor biology (ELN risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization) and ICU admission during intensive chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, as well as treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.
Non-secretory multiple myeloma (NSMM) constitutes a distinct entity of multiple myeloma characterized by the absence of detectable monoclonal protein and rarely an absence of free light chains in the serum and urine. Given its rarity, the genomic landscape, clinical course, and prognosis of NSSM are not well characterized. Here, we report a case of a patient with relapsed and refractory NSMM with brain metastasis harboring a TFG-ALK fusion showing a dramatic and durable (over two years) response to commercially available anaplastic lymphoma kinase (ALK) inhibitors. The case emphasizes the beneficial role of molecular profiling in this target-poor disease.
There is a paucity of large‐scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly‐diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60–88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale‐Geriatrics (CIRS‐G) score was 6 (range, 0–27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high‐dose methotrexate (HD‐MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R‐MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58‐month median follow‐up, median progression‐free survival (PFS) and overall survival (OS) were 17 months (95% CI 13–22 months) and 43 months (95% CI 31–56 months), respectively. Three‐year PFS and OS were highest with MTR (55% and 74%, respectively). With single‐agent methotrexate ± rituximab, 3‐year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS‐G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3‐year PFS was 65% versus 45% without maintenance (p = 0.02), with 3‐year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD‐MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.
Background: Non-Hispanic Black (NHB) and Hispanic patients with Acute Myeloid Leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite lower incidence, more favorable genetics, and a younger age at presentation (Darbinyan, Blood Adv. 2017). We performed a multilevel analysis of disparities in AML patients to investigate the contribution of structural violence, specifically neighborhood SES, on racial/ethnic differences in leukemia-specific survival. Methods: Adult AML (non-APL) patients diagnosed between 2012 and 2018 at six academic cancer centers in the Chicago area were included. Census tract data was collected using the FFIEC Geocoding/Mapping System and computed tract disadvantage and tract affluence scores were categorized into distribution tertiles (low, moderate, high). Time to relapse and death from leukemia were examined, adjusting for age, gender and race/ethnicity (baseline models), and for potential mediators of racial disparities including distal (Charlson Comorbidity Index (CCI), obesity, concentrated disadvantage and affluence, health insurance status), and proximal mediators (somatic mutations, and European Leukemia Network (ELN) prognostic score categories). Results Patient characteristics are shown in Table 1 (n = 822). Significant heterogeneity in age and comorbidities at diagnosis was observed, with Hispanic patients being the youngest and with the lowest CCI. Morbid obesity was more prevalent in NHB and Hispanic (23% and 20%, respectively) compared with NHW (11%) patients. Payer source also differed significantly; private insurance was twice as frequent among NHW than NHB (51% vs. 25%) patients, while the largest uninsured population was Hispanic. ELN adverse risk disease was most prevalent in NHW subjects, NPM1 mutations were least prevalent in Hispanic patients, and p53 mutations more prevalent in NHB (26%) compared to NHW (12%) and Hispanics (9%) although due to low numbers this did not reach significance (p=0.10). NHB and Hispanic patients tended to reside in more disadvantaged and less affluent areas. Treatment data was available for 764 patients (Table 2); 75% received intensive induction therapy and choice of first-line treatment did not differ by race or tract disadvantage. Allogeneic transplant rates however differed by race, age, insurance status, tract disadvantage, and ELN score. Treatment complications of induction chemotherapy, as reflected by ICU admissions during induction, were significantly lower in NHW (25%) compared to NHB (39%) and Hispanic (42%) patients. ICU admission rates were significantly higher in patients with morbid obesity and low tract affluence. Minority (vs. NHW) ethnicity was associated with a 42% increased hazard of death from leukemia (HR=1.42, 95% CI: 1.09, 1.85), and a 36% increased hazard of death from all causes (HR=1.36, 95% CI: 1.07, 1.72), each after controlling for age, gender and study site. Adjustment for continuous tract disadvantage and affluence and their interaction lowered both the hazard of leukemia and all cause death to 1.18 (95% CI: 0.88, 1.60) and 1.14 (95% CI: 0.88, 1.49), respectively. In formal mediation analysis, neighborhood SES accounted for 37% (p=0.09) and 50% (p=0.02) of the racial disparity in death from leukemia and all causes, respectively. Discussion: This study is the first to integrate data at the individual patient level with neighborhood characteristics, using census tract level variables to examine their contribution to AML patient outcomes. To date, formal mediation methods had not been employed to disentangle race/ethnic disparities in adult AML survival. Notably, our mediation analysis shows that census tract level SES explains a substantial proportion of the disparity in hazard of leukemia death. In addition, the observed disparities in treatment complications of induction chemotherapy, as reflected by ICU admissions, and the continued disparity in allogeneic transplant utilization all warrant further study. These results draw attention to the need for deeper investigation into the social and economic barriers to successful treatment outcomes for leukemia patients and represent an important first step toward designing strategies to mitigate these persistent health inequities. Disclosures Altman: Janssen: Consultancy; Syros: Consultancy; Genentech: Research Funding; Novartis: Consultancy; Amphivena: Research Funding; Amgen: Research Funding; Aprea: Research Funding; ImmunoGen: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Fujifilm: Research Funding; Kartos: Research Funding; AbbVie: Other: advisory board, Research Funding; Kura Oncology: Other: Scientific Advisory Board - no payment accepted, Research Funding; BioSight: Other: No payment but was reimbursed for travel , Research Funding; Daiichi Sankyo: Other: Advisory Board - no payment but was reimbursed for travel; Agios: Other: advisory board, Research Funding; Glycomimetics: Other: Data safety and monitoring committee; Astellas: Other: Advisory Board, Speaker (no payment), Steering Committee (no payment), Research Funding; Theradex: Other: Advisory Board; Immune Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy; France Foundation: Consultancy; PeerView: Consultancy; PrIME Oncology: Consultancy; ASH: Consultancy; Cancer Expert Now: Consultancy. Stock:Research to Practice: Honoraria; UpToDate: Honoraria; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Society of Hematology: Honoraria; Leukemia and Lymphoma Society: Research Funding; Novartis: Research Funding; Abbvie: Honoraria, Research Funding; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Quigley:Alnylam: Speakers Bureau; Agios: Speakers Bureau; Amgen: Other: Advisory board. Khan:Celgene: Consultancy; Incyte: Honoraria; Takeda: Research Funding; Amgen: Consultancy.
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