bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced care planning (ACP) intervention for older patient with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
Authors: LoCastro Marissa , Sanapala Chandrika , Watson Erin , Kluger Benzi , Norton Sally , Bernacki Rachelle , Carroll Thomas , Klepin Heidi D. , Mendler Jason , Loh Kah Poh
Published: June 2022

e19004

Background: The Serious Illness Care Program (SICP) is an evidence-based intervention that promotes ACP for patients with advanced cancer. As part of a study to adapt the SICP for older patients with AML and MDS, we identified clinician and patient reported barriers to ACP for this population, and their suggestions to improve ACP. Methods: In single-center qualitative study, we conducted semi-structured interviews with 14 oncology clinicians and 7 patients with AML or MDS. Interviews were audio-recorded and transcribed. Two investigators independently coded all transcripts using MAXQDA and resolved discrepancies through iteration. Direct content analysis techniques were used to focus on ACP barriers and suggestions. Results: Mean ages of clinicians and patients were 45 and 73, respectively. Majority of patients were not familiar with ACP. All patients had a healthcare proxy. Half of patients were familiar with a Medical Orders for Life-Sustaining Treatment (MOLST) form. Two major themes identified by clinicians and patients were: 1) Discomfort and logistics as ACP barriers (Table) and 2) ACP visit structure. Both clinicians and patients suggested the importance of earlier ACP visits. Clinicians suggested separate outpatient ACP visits, while patients suggested ACP after in-depth treatment discussion. Conclusions: Discomfort and logistics were identified as major barriers to ACP. Initiating ACP earlier was identified as a possible solution by clinicians and patients. Feedback obtained will be used to adapt the SICP to be delivered via Telehealth in a single arm pilot study.[Table: see text]
Characteristics of Medicare patients with relapsed/refractory acute lymphoblastic leukemia initiating treatment with inotuzumab ozogamicin, blinatumomab, or other agents.
Authors: Russell-Smith T. Alexander , Shah Richa , Silverstein Alison R. , Petrilla Allison A. , Leinwand Brian , Norris Diane , Schroeder Amy L
Published: June 2022

e19009

Background: B-cell precursor acute lymphoblastic leukemia (ALL) represents the majority of ALL cases. The INO-VATE and TOWER trials demonstrated that adult patients with relapsed/refractory (RR) B-cell precursor ALL treated with inotuzumab ozogamicin (ino, anti-CD22 monoclonal antibody [mAb]) and blinatumomab (blin, CD19-directed CD3 T-cell engager mAb), respectively, had improved clinical outcomes over chemotherapy. Real-world data on older RR ALL patients initiating CD-targeted therapy is limited. We describe characteristics, healthcare resource utilization (HRU), costs for Medicare beneficiaries with RR ALL initiating ino, blin, or other (chemotherapeutic, tyrosine kinase inhibitor [TKI], or mAb) therapies. Methods: Retrospective study utilizing Medicare enrollment/claims data. Eligible study patients diagnosed with RR ALL 1/1/2017-6/30/2019 and initiated ino, blin, or other at/after diagnosis (first observed treatment = index date). Claims for ino/other patients only visible in outpatient/pharmacy settings; proportion who received inpatient administration prior to outpatient unknown. Blin identifiable in inpatient + outpatient settings. B/T-cell status not captured; patients receiving T-ALL therapy (nelarabine) excluded. Measures included characteristics/HRU during 6 months pre-index and HRU/costs per patient per month (PPPM; costs in 2021 USD) during variable follow-up period (≥3 months until death, disenrollment, or study end). Results: Of 15,586 Medicare beneficiaries with RR ALL, 2,306 (< 15%) initiated an ALL treatment; 1,329 qualified for study inclusion: 55 (4%) received ino, 209 (16%) blin (73% initiated blin during hospital stay), 1,065 (80%) other. Mean age of ino/blin was 62; other 66. Larger proportion of ino cohort qualified for Medicare with non-age-related factors (disability) than blin/other. Treatment groups comparable by sex/race. Ino cohort had higher prevalence of congestive heart, pulmonary, and renal diseases (35%, 31%, 38%) than blin (19%, 25%, 19%), other (23%, 30%, 21%), respectively; diabetes prevalence was lower for ino than for blin/other (20%, 34%, 36%, respectively). Over 6 months pre-index, there was variability in exposure to cytotoxic chemotherapies, mAbs, TKIs by cohort;76% each of ino/blin cohorts, 66% of other cohort were hospitalized for any reason. Follow-up time (months) varied by cohort: 8.0 ino, 12.8 blin, 17.8 other, during which blin patients had higher PPPM rates of hospital stays, longer stays (9.3 days blin, 6.0 ino, 3.9 other), and higher mean (SD) total cost of care: $65,437 ($155,664) blin, $55,995 ($36,688) ino, $17,520 ($22,720) other. Conclusions: During 2017-2019, < 15% of Medicare beneficiaries with RR ALL received ALL treatment, of which 1 in 5 received CD-targeted therapy. Costs were highest for blin followed by ino then other.
Whole-genome sequencing as an alternative to analyze copy number abnormalities in AML, MDS and MM.
Authors: Lyu Xiaodong , Li Tao , Zhu Dandan , Cheng Yuexin , He Xiangxiang , Li Zhenling , Li Shiyong , Geng Shuaipeng , Yao Chunxiao , Li Jingshuai , Li Yangwei , Chang Yinyin , Zhu Zunmin , Mao Mao , Song Yongping
Published: June 2022

e19023

Background: Genomic alternations especially copy number aberrations (CNAs) are particularly imperative for diagnostic classification and risk stratification in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and multiple myeloma (MM). With the technological advances of next generation sequencing (NGS), the current CCA test and the molecular tests are likely to be challenged by whole-genome sequencing (WGS), which is a more unbiased method to detect all types of genomic aberrations. Methods: 178 patients who met the clinical manifestations of blood malignancies were included in the study, including 89 patients with AML, 48 with MDS and 41 with MM. Bone marrow was collected and mononuclear cells were separated to harvest genomic DNA which was sequenced without capture at approximately 1x coverage depth (shallow whole-genome sequencing, sWGS). Genome-wide CNAs greater than 5 Mbp was analyzed for each sample. European Leukemia Net (ELN), Revised International Prognostic Scoring System (IPSS-R) or Revised International Staging System (R-ISS)-defining CNAs were selected and used to assign patients to a genetic risk group through the same classification systems that are used for CCA. Results: In this study, CNA events were identified in 109 (73.6%) patients via sWGS. By calculating frequencies of recurrent gains and losses at chromosome arm level, some recurrent events were detected like gains of chr 8 (observed in 12 AML and 9 MDS patients), chr 1 (observed in 18 MM patients), losses of chr 7 (observed in 9 AML and 3 MDS patients) and chr 13 (observed in 16 MM patients), which were consistent with previously reported cytogenetic events. Besides, amplifications of odd-numbered chromosomes were detected in 15(36.6%) of patients with multiple myeloma, including chromosomes 3, 5, 7, 9, 11, 15, 19 and/or 21. And the trisomy of chr 5, 7 or 9 are mainly observed with a frequency of 66.7%. Among 145 patients with CCA results, a high concordance of 97.7% (98.5%, 97.6% and 97.1% in AML, MDS and MM respectively) was achieved in CNA profiles at individual patient level with cytogenetics and/or FISH. Noteworthily, CNA events were detected in 20 of 28 (71.4%) MM patients with negative karyotyping results. Moreover, sWGS improved the overall diagnostic yield by reassign 18 patients (9 with AML and 9 with MDS) to risk categories with poorer prognosis. Nearly identical CNA profiles from the paired plasma and bone marrow suggest that peripheral blood may serve as a substitute to spare bone marrow aspiration. Conclusions: In summary, a streamlined sWGS provides an accurate, convenient and cost-effective approach to describe genomic profiles of CNAs in patients with AML, MDS and MM. Clinical trial information: ChiCTR2100052276.
Phase II study of lower-intensity frontline therapy for newly diagnosed patients with AML who are unfit or otherwise not eligible for frontline clinical trials.
Authors: Venugopal Sangeetha , Jabbour Elias , Pemmaraju Naveen , Montalban-Bravo Guillermo , Chien Kelly Sharon , Daver Naval Guastad , Jain Nitin , Burger Jan Andreas , Alvarado Valero Yesid , Maiti Abhishek , Dinardo Courtney Denton , Borthakur Gautam , Malla Rashmi , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop M. , Kadia Tapan M.
Published: June 2022

e19028

Background: Pts with newly diagnosed(ND) AML often present with abnormal organ function, poor performance status (PS), concurrent active malignancies, and active infections precluding them from enrolling on frontline clinical trials, since standard eligibility routinely exclude them. We designed a lower-intensity regimen of cladribine plus low-dose cytarabine (LDAC) alternating with decitabine with less stringent inclusion criteria in ND pts unfit or ineligible for existing clinical trials. Methods: Pts >18 years with untreated AML and ineligible for other frontline AML clinical trials were enrolled (NCT01515527). Eligibility criteria included either creatinine ≥2mg/dL; or total bilirubin ≥2 mg/dL; active concurrent cancer, infection, or ECOG PS of 3 or 4; or ineligible for participation in a higher priority protocol. Induction was cladribine 5 mg/m2 IV on D1-5, Cytarabine 20 mg SQ twice daily on D 1-10, followed by consolidation with cladribine 5 mg/m2 IV on D1-3, Cytarabine 20 mg SQ twice daily on D 1-10 alternating with decitabine 20 mg/m2 IV, daily on D 1-5. Primary objective was 60-d survival rate. Results: 25 pts have been enrolled. The median age was 73 yrs (range, 52-82) with 76% aged ≥70 yo. 6 pts (24%) had concurrent active malignancy, 4 (16%) had baseline creatinine >2mg/dL, and 9 (36%) had PS ≥3. 76% were adverse risk per ELN 2017 (Table). Among 25 evaluable pts, 17 (68%) achieved a composite complete response (CRc) including 10 (40%) CR and 7 (28%) CR with incomplete count recovery (CRi). Among responders, 6 pts (35%) achieved MRD neg by flow. Of 7 pts with no response, all were ELN adverse risk. Median cycles to response was 1 (range: 1 - 4). 30- and 60 d mortality was 8% and 16%, respectively, including 2 pts (8%) who died due to pseudomonal sepsis on D8, and the other due to pneumonia on D11. At a median follow up of 9.4 months (range, 0.4- 19.9 m),median OS (6-mo OS% - 61 %), and EFS was 8.3 mo each (6-mo RFS% - 56 %) with a 60-d OS and EFS rate of 83% each, with a median RFS of 5.8 mo (2-mo RFS%-66%; 6-mo RFS% - 49 %). In this challenging patient population, this lower-intensity regimen was well tolerated, with an acceptable toxicity profile. Conclusions: In an unfit patient population of ND AML with high comorbidity burden, that were ineligible for other clinical trials, induction therapy with Cladribine plus LDAC was feasible and effective and can allow pts to achieve remission and move on to effective post-remission therapy. Clinical trial information: NCT01515527. [Table: see text]
Risk, overall survival, and prognostic analysis of therapy-related acute myeloid leukemia in non-Hodgkin lymphoma survivors.
Authors: Joshi Utsav , Gaire Suman , Bhattarai Adheesh , Agrawal Vishakha , Poudyal Bishesh Sharma , Bhatt Vijaya Raj
Published: June 2022

e19037

Background: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. tAML demonstrates high risk characteristics and poorer outcomes compared with de novo AML. We aimed to quantify the risk of tAML in NHL, determine factors associated with overall survival (OS) in tAML, and compare them with de novo AML. Methods: Patients with a histologic diagnosis of NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 database. AML that developed at least 1 year after the diagnosis of NHL was classified as tAML. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software (version 8.3.9) were used to calculate SIR and absolute excess risk (AER) of tAML based on - age, sex, race, year of diagnosis, chemotherapy, radiotherapy, and interval from NHL diagnosis. The 95% confidence intervals (CI) and p-values were generated using multivariate Poisson regression model. OS of both tAML and de novo AML was assessed using Kaplan Meier curves and then compared using log rank test. The roles of various factors on OS in tAML and de novo AML were evaluated using multivariate cox proportional hazard regression. Results: A total of 373 patients with tAML (N for NHL = 301,903) and 23,360 patients with de novo AML were included in the analysis. More de novo AML cases were ≥70 years compared to tAML (41.1% vs 32.7%, p < 0.001). The risk of development of tAML was significantly higher in ages < 60 years compared to 60-69 years and ≥70 years (SIR 14.0, 95% confidence interval [CI] 11.79-16.51 vs SIR 4.87, 95% CI 4.00-5.86 vs SIR 2.80, 95% CI 2.32-3.34, p < 0.0001). Patients who received chemotherapy were more likely to develop tAML than the non- recipients (SIR 8.44, 95% CI 7.51-9.44 vs SIR 1.75, 95% CI 1.37-2.21, p < 0.0001). The risk of tAML was higher within 5 years of NHL diagnosis (SIR 5.05, 95% CI 4.49-5.67 vs SIR 4.39, 95% CI 3.49-5.45, p < 0.001). There was no statistically significant difference in SIR based on sex, race, receipt of radiotherapy, and year of diagnosis. The median OS and 5-year OS were- 8 months and 13.1% for tAML and 10 months and 27.6% for de novo AML. On multivariate analysis, tAML was not found to be an independent predictor of OS (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years (age 60-69 years: HR 1.53, 95% CI 1.08-2.15, p = 0.01, age ≥70 years: HR 1.93, 95% CI 1.40-2.66, p < 0.001) and no chemotherapy (HR 1.82, 95% CI 1.40-2.35, p < 0.001) were associated with poor OS in tAML subcategory. Conclusions: Our large population-based study shows increased risk of tAML within the first 5 years of NHL diagnosis, younger NHL survivors, and chemotherapy recipients. Older age and no chemotherapy predispose to dismal OS in tAML.
Non-variceal upper gastrointestinal bleeding in patients with acute leukemia.
Authors: Mansour Mahmoud , Obeidat Adham E. , Abu-Farsakh Yomna , Mahfouz Ratib , Darweesh Mohammad , Ghous Ghulam , Tahan Veysel
Published: June 2022

e19041

Background: Patients with acute leukemia are prone to various hemorrhages, most frequently due to thrombocytopenia from disease activity or chemotherapy. However, there is minimal literature evaluating non-variceal upper gastrointestinal bleeding (NVUGIB) in leukemia patients. This study evaluates the outcomes of NVUGIB in hospitalized acute leukemia patients. Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between Jan 1st, 2016, to Dec 31st, 2019. Using International Classification of Diseases 10th revision codes, we identified adults with a discharge diagnosis of NVUGIB and a concomitant acute leukemia diagnosis, acute myelogenous leukemia and acute lymphoblastic leukemia. The control group included non-leukemia patients with NVUGIB. Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS), hospital charges, and effect of early esophagogastroduodenoscopy (EGD) within the first 24 hours of admission. Multivariate logistic regression was used to adjust for comorbidities and demographic variables. Results: A total of 1,208,885 discharges were identified with NVUGIB. Of those, 1019 had acute leukemia. Leukemia patients had higher mortality than the general population (12.5% vs. 3%, respectively; P <0.01). After adjusting for comorbidities and demographic variables, acute leukemia patients had significantly higher mortality (adjusted odds ratio [AOR] 3.75, 95%CI 2.37-5.94 P <0.01). Mean length of stay and hospital charges increased by 6.87 days (95%CI 3.99-9.75, P < 0.01) and 128,437$ (95%CI 68,633$-188,240$, P < 0.01), respectively, in the acute leukemia group. Additionally, acute leukemia patients who had an early EGD had significantly less mortality, length of stay, and hospital charges compared to delayed EGD as shown in the attached table. Conclusions: Acute leukemia patients admitted with NVUGIB have significantly higher in-hospital mortality and health care burden. Early EGD in these patients is associated with lower in-hospital mortality, shorter length of stay, and lower total hospital costs. However, given the retrospective nature of this study, we cannot determine that early EGD is a causal factor for the improved outcomes. Future prospective studies will be required in acute leukemia patients admitted with NVUGIB to further evaluate these findings.[Table: see text]
A national inpatient sample analysis for CAR-T cell therapy administration.
Authors: Bakalov Veli , Tang Amy , Helfand Alexander M , Kancharla Pragnan , White Richard , Khattab Ahmed , Alhousani Mohammad , Samhouri Yazan
Published: June 2022

e19501

Background: Chimeric antigen receptor T-cell therapies (CAR-T) improve relapse free survival and durable remission rates in patients with relapsed/refractory large B-cell lymphoma (LBCL) and received US FDA approval in 2017. The cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity (ICANS) due to CAR-T cell therapy require close inpatient monitoring. Real world data are lacking regarding the cost of hospitalization, length of stay (LOS), toxicity, and mortality associated with CAR-T. The goal of this study was to analyze the clinical outcomes of inpatient CAR-T utilizing a national database. Methods: Data was collected from the 2018 version of the Nationwide Inpatient Sample (NIS) database. Patients who received CAR-T were identified with ICD-10 disease and procedure codes . Complex weights were used to enable appropriate national projections. The association between toxicity (particularly related to CRS and ICANS) and outcomes was examined using logistic regression analyses (p < 0.05 statistically significant). SAS v9.4 (SAS Institute, Cary, NC) was used for data analysis. Results: 306 patients met selection criteria. Demographic criteria were as follows: 61.1% males, 62.4% white, median age 58.0 years old (IQR 45.2-65.0), and private insurance (56.9%). A majority received care at urban teaching (97.7%) and large hospitals (73.2%). Relevant complications during hospitalization included hypotension (24.5%), pneumonia (8.5%), sepsis (9.8%), seizure (5.9%), neutropenia (24.5%), thrombocytopenia (8.8%), tumor lysis syndrome (TLS) (3.3%), and acute kidney injury (AKI) (14.1%). Median LOS was 16 days (IQR 12.0-22.0), median charge for hospitalization was $493,887 USD (IQR 143,400.0-1,182,940.0), and inpatient mortality was 5.2%. On multivariate regression analysis, inpatient mortality was significantly higher in those with intubation (OR 30.1, 95%CI 3.45-262), sepsis (OR 9.49, 95%CI 1.48-60.7), TLS (OR 18.9, 95%CI 2.52-140), AKI (OR 24.7, 95% CI 1.37-447) and thrombocytopenia (OR 53.4, 95% CI 2.19-1,298). LOS was higher in those with blood transfusion (OR 1.29, 95% CI 1.08-1.53), sepsis (OR 2.04, 95% CI 1.59-2.61), pancreatitis (OR 2.03, 95% CI 1.09-3.77), pneumonia (OR 1.39, 95%CI 1.04-1.87) and treatment in urban teaching hospitals (OR 1.53, 95%CI 1.02-2.30). Increased hospitalization charges were associated with hypotension (OR 1.54, 95%CI 1.14-2.08) and with treatment at urban teaching hospitals (OR 7.46, 95%CI 4.67-11.9) and medium size hospitals (OR 1.49, 95%CI 1.04-2.15). Conclusions: Inpatient mortality, median LOS, and hospitalization charges in inpatients treated with CAR-T can be significantly increased not only by inpatient complications, but also by the size and type of the treating facility. These findings highlight the financial burden of CAR-T cell therapy in the real world and can be used to shape future healthcare policy.
A sensitive and robust bioanalytical assay for pharmacokinetic analysis of ROR1xCD3 bispecific T cell engager (NVG-111) in a first-in-human study.
Authors: Shah Mittal , Granger David , Bobrzynski Tomasz , Baccaro Annalisa , Gore Jasmine , Muczynski Vincent , Cook Sarah , Chester Kerry , Batten Toby , O'Donovan Kieran , Jasani Parag , Nathwani Amit C.
Published: June 2022

e19505

Background: Receptor tyrosine kinase-like Orphan Receptor-1 (ROR1) is widely expressed on hematological and solid tumors. NVG-111, a first in class humanized tandem scFv ROR1xCD3 bispecific antibody elicits potent killing of ROR1+ tumor cells in vitro and in vivo. This bispecific T-cell engager (TCE) is being evaluated in a first in human, Phase I trial in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The predicted therapeutic dose and steady state serum concentrations of NVG-111 were estimated by allometric scaling using relevant doses from a murine PK study. To assess free drug levels in patients following 21 days of continuous infusion of NVG-111, a bespoke, sensitive pharmacokinetics (PK) assay with high levels of specificity and sensitivity was developed. Methods: Anti-idiotype (anti-ID) antibodies directed to anti-ROR1 (αROR1-ID) and anti-CD3 (αCD3-ID) were generated by mouse immunization or by phage display from customized libraries. A proof-of-concept sandwich ELISA assay was developed using αCD3-ID to capture NVG-111 and detection by biotinylated hROR1-streptavidin-HRP. Gyrolab and Quanterix Simoa high sensitivity ELISA platforms were used to detect NVG-111 by αCD3-ID capture and αROR1-ID detection. The mesoscale discovery electrochemiluminescence assay (MSD-ECLA) was developed using a reversed format; NVG-111 capture with αROR1-ID and detection with αCD3-ID. Results: Allometric scaling predicted a theoretically relevant therapeutic dose and steady state serum concentration of 1ng/mL NVG-111 in humans, which was just at the level of sensitivity of a conventional ELISA under non-matrix conditions. Transferring the format to Quanterix Simoa had limited success due to high background levels in all configurations evaluated. The Gyrolab platform increased sensitivity to 75pg/mL, but suboptimal individual human sera matrix selectivity limited assay validity. Assessment of MSD-ECLA provided the best signal/noise, enhanced human disease and healthy sera selectivity, and a dynamic sensitivity range of 250pg/mL to 32ng/mL, which enabled the development of a GCLP qualified PK assay. The MSD-ECLA assay was employed to measure NVG-111 concentrations in CLL or MCL subjects dosed with 0.3-30µg/day NVG-111. MSD-ECLA detected drug in patients receiving NVG-111, with a range of steady-state serum concentrations (Cavg.ss) of 168-610pg/mL. This was in-line with the predicted drug levels from the single species allometric scaling, albeit with observed levels being marginally lower than expected. Conclusions: Development, custom optimization and validation of a highly sensitive MSD-ECLA PK assay has enabled GCLP-compliant measurement of circulating NVG-111 in CLL or MCL patients treated with at least 10µg/day cIV NVG-111.
Survival trends among patients diagnosed with both melanoma and chronic lymphocytic leukemia.
Authors: Zhao Yayi , Amorrortu Rossybelle , Stewart Sandra C. , Ghia Kavita , Williams Vonetta L. , Sondak Vernon K. , Tsai Kenneth Yee , Pinilla-Ibarz Javier , Chavez Julio C. , Rollison Dana Elise
Published: June 2022

e19527

Background: Patients previously diagnosed with melanoma have a higher risk of developing subsequent chronic lymphocytic leukemia (CLL). Similarly, melanoma risk has been observed to be elevated among patients with a history of CLL. However, previous studies have reported inconsistent results on whether being diagnosed with both cancers significantly reduces patient survival. Additional research is needed to assess the potential reduction in survival among this unique cohort of patients diagnosed with both melanoma and CLL. In addition, the timing of the cancer development needs to be assessed to further explore unique patient characteristics. Methods: A retrospective cohort study was conducted using data from adult patients who were diagnosed and/or treated for melanoma (n = 5,511) or chronic lymphocytic leukemia (CLL, n = 571) at Moffitt Cancer Center (MCC) in 2008-2020. Clinical characteristics and survival information were obtained from the MCC Cancer Registry including, date of diagnosis, vital status, time of death or last contact, and tumor stage at diagnosis. The Kaplan-Meier method was used to estimate survival for three patient groups: patients diagnosed with only melanoma, patients diagnosed with only CLL, and patients who were diagnosed with both cancers. The timing of the two cancer diagnoses were assessed among the 17 patients diagnosed with both melanoma and CLL. Results: The estimated 5-year survival was 78.5% and 82.9% among patients diagnosed with only melanoma and only CLL, respectively. Among patients who were diagnosed with both cancers, the 5-year survival since melanoma diagnosis was 61.4% whereas the 5-year survival since the CLL diagnosis further reduced to 60.2%. When analyzing the timing of the diagnoses of the two cancers, 13 out of 17 patients were diagnosed with melanoma prior to CLL. Further, among these 13 patients, 12 patients had CLL diagnosed within 100 days after the melanoma diagnosis. Conclusions: Patients diagnosed with both melanoma and CLL experienced poorer survival outcomes as compared to patients who were diagnosed with only one of these cancers. Among patients who were diagnosed with both cancers, more than 70% of the patients were diagnosed with CLL shortly after their melanoma diagnosis. Additional research using larger national cancer registry databases can help to advance the understanding of the underlying disease mechanism and confirm the observed timing of diagnoses is due to the CLL being diagnosed incidentally as result of node biopsies for melanoma.
Clinical characteristics and outcomes of newly diagnosed patients with human immunodeficiency virus-associated lymphoma administered highly active antiretroviral therapy: Central and Western China AIDS Lymphoma League 001 study (cw-CALL 001).
Authors: Wang Chaoyu , Liu Jun , Lei Haike , Wu Yongzhong , Liu Yao
Published: June 2022

e19535

Background: HIV-associated lymphoma is the most common subtype of HIV-associated cancers, with a very low incidence. To date, there are only few retrospective studies analyzing the clinical features and prognosis of HIV-associated lymphoma. Therefore, we performed a study to analyze the clinical characteristics and outcomes of newly diagnosed HIV-associated lymphoma patients in our center, as the largest HIV-associated lymphoma cohort in China so far. Methods: Totally 107 newly diagnosed HIV-associated lymphoma patients in Chongqing University Cancer Hospital, Southwest China, from July 2008 to August 2021, were analyzed. Results: In the 107 HIV-associated lymphoma cases, median age was 49 years (range: 23–87 years), and more patients were male (87.9%). Most patients had elevated lactate dehydrogenase (LDH) (78.5%), elevated β2-MG (91.6%), advanced Ann Arbor stage (73.8%) and high IPI score (IPI score: 3-5) (62.7%) at diagnosis. Totally 46 patients (43%) had one or more sites of extranodal involvement, of whom 24 (22.4%) possessed two or more extranodal sites. Median CD4+ T cell count at diagnosis was 191/μl (range: 4-1022); 84 patients (78.5%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. Of the 72 patients evaluated at the end of treatment, the overall response rate (ORR) was 81.9% (59/72); 29 (40.3%) cases achieved complete response (CR), 30 (41.7%) had partial response (PR) and 9 (12.5%) experienced progressive disease (PD). In 99 HIV-associated lymphoma cases with complete follow-up data (median follow-up of 44.5 months [range: 2-160 months]), median PFS and OS were 36.0 months and not reached, respectively. The overall 5-year PFS and OS rates were 46.9% and 53.4%, respectively. Compared with individuals not administered anti-lymphoma treatment or administered less than 3 cycles anti-lymphoma therapy, those who received standardized anti-lymphoma therapy (≥3 cycles) showed improved PFS ( p=0.0006) and OS ( p<0.0001). In patients administered systemic anti-lymphoma therapy, the overall 2-year PFS rates for chemotherapy and R-chemotherapy were 29.5% and 67.1%, respectively (HR=0.44, 95%CI 0.210-0.927; p=0.020). The overall 2-year OS rates for chemotherapy and R-chemotherapy were 51.9% and 73.1%, respectively (HR=0.42, 95%CI 0.183-0.969; p=0.042). Conclusions: Overall, these data indicated that HIV-associated lymphoma has aggressive characteristics, including advanced Ann Arbor stage, high IPI score, more extranodal involvement and elevated LDH. Survival is significantly improved due to the wide use of cART and chemoimmunotherapy. Standardized anti-lymphoma therapy is significantly associated with superior outcomes. Clinical trial information: ChiCTR2100054581.
Clinicopathological features and management of patients with primary CNS lymphoma: Peruvian experience in two cancer centers.
Authors: Castro-Mollo Melanie Wendy , Diaz Alonso , Roque Perez Katia , Meza Jessica Gabriela , Quintana Truyenque Shirley Milenca , Peña Estefanía , Lopez Lourdes , Barrionuevo Carlos , Mallma Soto Víctor Iván , Dueñas Daniela , Alcarraz Cindy Elizabeth , Vidaurre Tatiana , Samanez Cesar Augusto , Vasquez Jule F
Published: June 2022

e19541

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and rare extranodal non-Hodgkin lymphoma with a dismal prognosis in most patients. Outcomes in Latin population is unknown. Methods: We present a retrospective cohort of fifty-five and six newly diagnosed Peruvian patients treated at the Instituto Nacional de Enfermedades Neoplasicas from 2000-2020 and at Oncosalud from 2014-2020, respectively. Inclusion criteria were (1) histologic diagnosis of diffuse large B-cell lymphoma by two pathologists; (2) disease localized exclusively in the brain, cranial nerves, meninges, or eyes; and (3) no evidence of human immunodeficiency virus infection. Results: Median age at diagnosis was 52 years old [range 21-76]. Sixty-one percent were men. Eastern Cooperative Oncology Group performance status was ≥2 in 68% of patients. Clinical presentation was characterized by intracranial hypertension symptoms (67%), focal deficit (64%), visual disturbance (18%), and seizures (9%). elevated LDH was present in 26/46 (57%) patients, multiple lesions in 19/56 (34%) patients, and involvement of deep structures 21/62 (34%) patients. Seven patients were treated by surgery only (3, subtotal and 4, total resection), three patients received radiotherapy only, and six patients did not receive any treatment. Forty-two patients received the following chemotherapy protocols: DeAngelis (26%), high-dose methotrexate (HD-MTX) (17%), HD-MTX + high-dose ARAC (HD-ARAC) (36%) and HD- MTX + HD-ARAC + Rituximab (9%), HD-MTX + Rituximab + Temozolomide (TMZ) as induction and consolidation with etoposide (VP16) + HD-ARAC (12%), the latter was used in the private center. Clinical outcomes are described in Table. The median follow-up time was 9m (0.03-248). The median overall survival (OS) was 9.9m, 5y OS was 41.7% (95% CI, 29.2-53.9). The median OS were 6.6m and 67.3m for the public and the private institution, respectively (p=0.02). 5y OS was 34% and 100% in the public and the private center, respectively. Conclusions: Peruvian patients are 15 years younger than those reported in the literature. OS in our cohort is dismal, being poorer in those patients treated at the public center reflecting treatment disparities between the public and private health system. All patients who received HD-MTX+HD-ARAC+TMZ as induction and VP16 +HD-ARAC as consolidation achieved complete response and the median OS was not reached although this can be explained due to a short follow-up time compared to those who received DeAngelis regimen. A longer follow-up is needed to demonstrate if polychemotherapy without radiotherapy is the best treatment in this group of patients.[Table: see text]
Patient preferences for second-line treatment options in diffuse large B-cell lymphoma: A discrete choice experiment.
Authors: Birch Kelly , Chiu Kevin , Baumgardner James , Snider Julia , Wade Sally West , Shah Gunjan L.
Published: June 2022

e19558

Background: Standard of care (SOC) treatment in second-line (2L) large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL), involves salvage chemotherapy followed by autologous hematopoietic cell transplant (AHCT) for those with chemo-sensitive disease. However, many patients do not respond adequately to chemotherapy or are otherwise ineligible for AHCT. Chimeric antigen receptor T-cell (CAR T) therapy is a promising 2L therapy for LBCL that differs from SOC agents in terms of mechanism of action, therapeutic benefit, and safety profile. Given these differences, this discrete choice experiment (DCE) quantified 2L treatment preferences among patients with DLBCL. Methods: We conducted an online DCE with patients with DLBCL residing in the United States (US) and Europe (United Kingdom, France, Italy, Germany, and Spain). Attributes of 2L treatments were parameterized based on clinical trial data and included the probability (percent of patients) of surviving one year after treatment, the change in survival rate from one to three years, the risks of severe cytokine release syndrome (CRS) and neurological events, the risk of severe infection, and expected time until the patient’s functioning would return to pre-treatment levels. A willingness-to-accept measure was used to assess how much of an increase in one-year survival was needed for a patient to accept elevated risks of severe CRS and neurological events, which can be associated with CAR T treatment. Results: A total of 224 patients were included in the analysis (US: 105; Europe: 119). The mean age of respondents was 50 years (range 34 - 76); 74% were male, and 94% were actively receiving cancer treatment. Patients considered the probability of surviving one year after treatment to be the most influential treatment attribute, followed by risk of severe CRS/neurological events. The third most influential attribute was the change in probability of survival for three years post-treatment for US patients and time needed to return to pre-treatment functioning for European patients. The willingness-to-accept calculation found that patients required a 13-14 percentage point increase in the probability of surviving one year to accept a 28% risk of a serious neurological event and a 13% risk of serious CRS. Conclusions: Patients with DLBCL showed their willingness to accept increased risks of CRS and neurological events to achieve a greater probability of survival. This preference tradeoff (efficacy over risk of adverse events) has been shown previously for lymphoma patients. Patients also valued a quicker return to baseline functioning, which is notable given recent data on the quicker recovery of quality of life with CAR T compared with SOC. These patient preferences provide important context for 2L LBCL treatment decisions, and may lead to shared decision-making that reflects both clinical and patient priorities.
Functional activity of peripheral blood mononuclear cells in patients with non-Hodgkin's lymphomas receiving treatment after COVID-19 disease.
Authors: Sagakyants Aleksandr B. , Lysenko Irina B. , Shulgina Oksana G. , Kamaeva Inna A. , Zolotareva Ekaterina I. , Novikova Inna A. , Vladimirova Liubov Yu , Kit Oleg I. , Dzhenkova Elena A. , Zlatnik Elena Yu , Dmitrieva Viktoria V. , Nikolaeva Nadezhda V.
Published: June 2022

e19564

Background: Patients with non-Hodgkin's lymphomas (NHL) develop abnormalities in the structural and functional organization of the immune system leading to immune deficiency. Chemotherapy (CT) in patients after SARS-CoV infection is associated with a more severe disease course affecting the treatment results. The cytokine-producing activity (CPA) of blood cells is poorly studied, while it determines the effectiveness of antitumor and anti-infective functions of the immune system. The purpose of this study was to evaluate CPA of peripheral blood mononuclear cells in patients receiving treatment for NHL after COVID-19. Methods: The study included 8 patients with large B-cell NHL with PCR-confirmed COVID-19 infection in past medical history. All patients received from 3 to 4 chemotherapy cycles. K2EDTA blood samples obtained before and after 3-4 CT cycles were divided into 2 parts after dilution with a sterile nutrient medium solution: part 1, to assess spontaneous CPA; part 2, with addition of a sterile mitogen (phytohemagglutinin 4 μg, concanavalin A 4 μg, and lipopolysaccharide 2 μg) to assess stimulated CPA. The samples were incubated for 24 hours at 370C, and the levels of IL-1β, IL-6, IL-8, IL-10, IL-18, IL-4, IL-2, TNF- α, INF-ɣ, INF-α were determined in the obtained plasma. The stimulation coefficient (SC) was calculated as the ratio of stimulated CPA to spontaneous CPA. Results: 3-4 CT cycles in patients after COVID-19 was accompanied by an elevation of spontaneous CPA of the blood cells IL-6, INF-ɣ, TNF-α, IL-8, compared to the initial levels, by 678%, 127%, 64% and 57%, respectively. The ability of cells to spontaneous production of IL-10 and INF-α decreased by 30% and 100%. The mitogen-induced CPA of mononuclear cells in relation to IL-10, IL-6, IL-2, IL-1β and INF-α increased by 300%, 130%, 92%, 52% and 52%, respectively. Stimulated CPA in relation to INF-ɣ decreased by 21% compared to initial levels. As a result of the revealed CPA changes, SC in NHL patients after COVID-19 receiving CT increased, compared to the initial levels, by 465%, 92% and 48% respectively for IL-10, IL-2, IL-1β, as well as the appearing ability to INF-α production. SC for IL-6, INF-ɣ, TNF-α, and IL-8 decreased by 70%, 66%, 33% and 27% respectively. Conclusions: Certain features of spontaneous and mitogen-activated CPA of blood mononuclear cells were revealed in NHL patients after COVID-19, indicating a change in the functional activity of immune cells which could affect the development of the disease and the effectiveness of the therapy. The data obtained require additional studies and can be used to assess the condition of patients, as well as to predict the therapy efficacy.
Clinical efficacy of daratumumab (DARA)-based second line therapy after DARA-containing and DARA-free induction therapies in multiple myeloma: A single center experience.
Authors: Ciardiello Amanda , Korde Neha , Hultcrantz Malin , Hassoun Hani , Mailankody Sham , Shah Urvi A , Lu Sydney X. , Patel Dhwani , Maclachlan Kylee , Lahoud Oscar Boutros , Shah Gunjan L. , Scordo Michael , Chung David J. , Landau Heather Jolie , Giralt Sergio , Derkach Andriy , Usmani Saad Zafar , Lesokhin Alexander M. , Tan Carlyn Rose Co
Published: June 2022

e20005

Background: DARA has been FDA approved for newly diagnosed multiple myeloma (NDMM) in combination with lenalidomide/dexamethasone (Rd), bortezomib/melphalan/dex, and bortezomib/thalidomide/dex since 2018. With the increase use of DARA combinations in NDMM, understanding the role of DARA retreatment at relapse needs to be examined in clinical practice. Herein, we describe a single institution experience of the efficacy of DARA-based retreatment as second line of therapy (LOT2) for patients (pts) who received DARA-based induction compared to DARA-free induction regimens. Methods: Thirty-three pts treated with DARA-based LOT2 at MSK from 1/2015 to 9/2021 were included in this retrospective analysis. Primary endpoint was overall response rate (ORR; ≥PR by IMWG criteria). Discrete patient characteristics were summarized by frequency (percentage) and continuous characteristics were summarized by median (IQR). Progression free survival (PFS) was evaluated by Kaplan-Meier method. Results: Two cohorts were identified based on prior DARA exposure: cohort 1 (N=6) received DARA-based induction without meeting DARA-refractory criteria and cohort 2 (N=27) had carfilzomib and Rd (KRd) induction (Table). Median follow-up was 13.8 and 14.5 months for cohorts 1 and 2, respectively. In cohort 1, 5 pts received DARA-KRd and 1 had DRd as first line therapy (LOT1). Median time between last dose of DARA in LOT1 and first dose of DARA in LOT2 was 17.5 months (IQR 12.1-19.8). ORR were 83% and 79% for cohorts 1 and 2, respectively. In cohort 1, ORR comprised of 1 sCR, 1 VGPR, and 3 PR. For cohort 2, there were 5 sCR/CR, 7 VGPR, and 9 PR. Median PFS was not reached in cohort 1 and 16.2 months in cohort 2. Conclusions: In a cohort of pts retreated with DARA after DARA-based induction, our findings suggest that DARA-exposed MM pts may derive benefit from DARA retreatment in subsequent lines of therapy similarly to pts who were DARA-naïve prior to DARA-based LOT2. Longer follow-up is needed to assess survival outcomes. In addition, larger confirmatory studies are warranted to further characterize response characteristics of DARA combinations in LOT2, especially as DARA-based therapy is increasingly used in treating NDMM. [Table: see text]
T-cell redirected bispecific antibodies in relapsed and refractory multiple myeloma: A systematic review and meta-analysis.
Authors: Waqar Syed Hamza Bin , Khanam Razwana , Rehman Mohammad Ebad Ur , Chattaraj Asmi , Ali Hassam , Anwer Faiz
Published: June 2022

e20014

Background: Multiple myeloma (MM) is a malignant plasma cell disorder which remains incurable, and in relapsed and refractory treatment, chimeric antigen receptor therapy shows promise. Bispecific antibodies (bsAbs) utilize the exact mechanism by engaging BCMA and other potential tumor-associated antigens on myeloma cells and T-cells. We have conducted a systematic review and meta-analysis to evaluate the efficacy and safety of bsAbs in heavily pretreated MM cohorts. Methods: We searched PubMed, Clinicaltrials.gov, Cochrane, Google Scholar, Embase, and major conferences (oral and poster presentation), with MeSH terms and keywords for “multiple myeloma” or “relapsed refractory multiple myeloma,” AND “bispecific antibody” or “BiTE”. We included all original studies reported in the English language published from inception until January 2022. After primary and secondary screening, eleven clinical trials were included. Pooled analysis was done with the help of random effects model (Freeman-Tukey Double Arcsine Transformation) in OpenMetaAnalyst software. Results: We identified nine phase I and two phase II trials (n=837), with a mean age of 64.5 years. Most cohorts being triple-, quad- or penta-refractory MM. Complete response (CR) or stringent CR (sCR) reported is 12% (95% CI 9-15.3%, I² 16.54%, n=66), very good partial response (VGPR) 14.8% (95% CI 8.3-22.7%, I² 80.57%, n=93) and partial response (PR) 11.8% (95% CI 0.2-3.41%, I² 93.21%, n=26). The overall response rate (ORR) reported is 59.5% (95% CI 44.7-73.5%, I² 90.71%, n=307). Among the most common adverse events anemia is seen in 44.2% (95% CI 38.1-50.4%, I² 17.86%, n=152), neutropenia in 33.8% (95% CI 18.4-51.2%, I² 93.27%, n=179), thrombocytopenia in 32% (95% CI 21.4-43.6%, I² 75.96%, n=113) and cytokine release syndrome in 57.1% (95% CI 45.5-68.4%, I² 85.63%, n=315). Conclusions: Bispecific antibodies have shown promising efficacy in relapsed and refractory MM cohorts with a very well safety profile. Upcoming phase II/III trials are much awaited, along with combination studies of bsAbs with other agents to gauge response.[Table: see text]
COVID-19 impact on multiple myeloma prescribing patterns.
Authors: Pittos Elias , Shah Dipti , McAuliff Kelly , McCarthy Amanda , Cavers William , Grover Rashmi , Feczko Lucia , Avalos-Reyes Elisea , Johnson Kjel Andrew
Published: June 2022

e20027

Background: COVID-19 has impacted several areas of oncology patient care, most notably the reduction of patient visits for treatments. Standard treatment of multiple myeloma (MM) involves a combination of intravenous (IV) and oral therapies. The purpose of this study is to assess the impact COVID-19 had on IV and oral medication prescribing patterns pre and during the COVID-19 pandemic among MM patients. Methods: This is a retrospective review of adult MM patients insured by a large commercial and Medicare health plan in the United States who started a new IV or oral MM agent during the study period. To assess the impact of COVID-19 on IV and oral medication prescribing patterns, we compareda pre-COVID period (March 1-August 31, 2019) to a COVID period (March 1-August 31, 2020). We utilized medical and pharmacy claims to identify patients and calculated new therapy starts per newly diagnosed patient (defined as the number of patients starting a new IV or oral medication for MM divided by the total number of patients with a first indication date of MM within the study timeframe). We compared rates using a Chi-square test; p-values ≤ 0.05 were considered statistically significant. Results: 1,754 patients were enrolled in the study; there were no significant differences in demographic characteristics pre and during COVID-19 between the two groups with respect to age (67.05 vs. 66.64; p=0.45), gender (p=0.80), insurance plan type (p=0.17), geographical region (p=0.26) and medication (p=0.59). During COVID-19, the number of newly diagnosed MM patients decreased by 22% (9,657 to 7,560) and the total number of new therapy starts decreased by 11% (930 to 824). When looking at rates of new therapy starts per newly diagnosed patient, both IV (11%; p=0.03) and oral (51%; p=0.03) medication rates significantly increased. Additionally, there were significant increases in new therapy start rates by region in the Northeast for oral (157%; p<0.01) and West for IV (32%; p=0.02) medications. There were no significant differences in new start rates by insurance plan type (all p>0.08). Conclusions: While the total count of new therapy starts, a proxy for new diagnoses, decreased during COVID-19, the rate of new starts for both IV and oral therapies for patients diagnosed with MM significantly increased. These increased start rates may be explained by a remarkable 22% drop in the total number of newly diagnosed MM patients during COVID-19. As the pandemic continues, further study is warranted to understand how COVID-19 may impact IV vs. oral usage in MM. [Table: see text]