ALBERT

Description: Background The inflammatory and immune response in tumor microenvironment plays a critical role in cancer progression. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor in solid and lymphoid malignancies. We explored the association of NLR with response to chemotherapy and overall survival (OS) in patients with relapsed/refractory acute myeloid leukemia (RR-AML). Methods A single-center retrospective study was conducted, including 63 adult RR-AML patients who underwent salvage therapy at the University of Wisconsin from 2009 to 2018. Demographic, clinical and pathologic factors were ascertained at the time of RR-AML diagnosis. Refractory AML was defined as failure to achieve remission and

Description: Background Induction therapy for acute myeloid leukemia (AML) with a cytarabine-anthracycline regimen (7+3) is well-established; however, there is no standard salvage therapy for patients with relapsed/refractory AML (RR-AML). There is a paucity of data regarding outcomes with salvage regimens in RR-AML that include cladribine, cytarabine, and filgrastim with mitoxantrone (CLAG-M) or without mitoxantrone (CLAG), and mitoxantrone, etoposide, and cytarabine (MEC). We compared outcomes of patients receiving CLAG-M, CLAG or MEC as salvage therapy for RR-AML. Methods A multi-center retrospective study was conducted, including 146 adult RR-AML patients who underwent salvage therapy at the University of Wisconsin and Medical College of Wisconsin from 2009 to 2018. Demographic, clinical and pathologic factors were ascertained at the time of RR-AML diagnosis. The Center for International Blood and Marrow Transplant Research (CIBMTR) response criteria were used. Refractory AML was defined as failure to achieve remission after one or more courses of induction chemotherapy. Minimal residual disease (MRD)-negative was defined by the absence of leukemic cells by morphology and flow cytometry (

Description: Introduction: Carfilzomib use as a single agent or in combination has been shown to improve outcomes in relapsed refractory multiple myeloma (RRMM). Traditionally, carfilzomib has been administered in twice-weekly dosage schemes as compared to the newly approved once-weekly dosage scheme. The once-weekly dosing of carfilzomib is thought to provide same efficacy and has been evaluated in many clinical trials. We have performed a systematic review of comparative efficacy and toxicity profiles of once and twice-weekly carfilzomib dosing schemes in RRMM. Materials and methods: Systematic review was done according to PRISMA statement. PubMed, Embase, AdisInsight, & Clinicaltrials.gov databases were searched, without any filters, using the search terms "Multiple Myeloma" AND "Kyprolis" OR "Carfilzomib". Most recent reports of phase I/II/III clinical trials reporting the clinical efficacy and/or safety of carfilzomib in RRMM were considered for inclusion. After screening of 267 articles, 16 clinical trials (N=2393) evaluating twice-weekly carfilzomib and 4 trials (N=418) evaluating once-weekly dosing schedule were considered for inclusion. Results Once versus (vs.) twice-weekly carfilzomib regimens were evaluated in a total of 406 and 1869 patients, respectively. In our discussion, group-1 refers to patients receiving once weekly carfilzomib while group-2 refers to twice weekly dosing schedule group. For the evaluated population, high risk cytogenetics were reported in 15% (n=60) patients in group-1 and in 17% (n= 317) patients in group-2. The median no. of prior lines of therapy ranged 1-8 in group-1 as compared to 1-20 in group-2. All studies reported the patient responses according to International Myeloma Working Group (IWMG) response criteria. The cumulative overall response rate (ORR) was better in group 1: 70.4% (n= 286) vs. 48% (n= 896). Similarly, more patients in group-1 achieved stringent complete response (sCR) or complete response (CR): 11.5% (n= 47) patients in group 1 vs. 5.2% (n= 99) patients in group 2. The response rates were also non-inferior in group-1 for other responses as overall. In group-1, 30% (n= 123) patients achieved very good partial response (VGPR) compared to 21% (n=389) patients in group-2. The partial response (PR) rate was 28.5% (n= 116) vs. 22% (n= 412) in groups 1 and 2 respectively The rate of minimal response (MR) achievement was comparable in both groups: 5% (n= 21) in group-1 vs. 8% (n= 154) patients in group-2. But lesser proportion of patients in group-1 went on to develop progression of myeloma disease [5.6% (n= 23) vs. 15.6% (n= 293)]. Stable disease (SD) state was achieved by 12.3% (n=50) patients in group-1 compared to 20% (n= 379) patients in group-2. Owing to phase-1 design of most clinical trials evaluating the once-weekly dosing schedule, the survival data is immature at present, but the median progression free survival (PFS) ranged from 1 day to 12.6 months in group-1 while in group 2 it ranged from 3.7-44.4 months. (Table-1) The toxicity profiles were also comparable for both dosing schedules. The most common hematological adverse events (AEs) were anemia and thrombocytopenia and their incidences were 15.7% (n= 64) vs. 25.5% (n= 477) and 13.3% (n= 54) vs. 23.1% (n= 432) in groups 1 and 2 respectively. The most common non-hematological AEs were infections, fatigue, and nausea that were reported in 22% (n= 89), 19% (n= 77), and 17.4% (n= 71) patients in group 1, and 14.5% (n= 272), 19.3% (n= 362), and 19.1% (n= 357) patients in group 2, respectively. Overall, grade 3 or above cardiac AEs were reported in 3.4% (n= 14) patients in group 1 and 3.3% (63/1869) patients in group 2. The most common cardiac AE was hypertension which constituted 50% (n= 7) and 64% (n= 40) of all grade 3 or more cardiac AEs in groups 1 and 2, respectively. Conclusion Achievement of objective response rates for once-weekly carfilzomib appears to be better or at-least similar to twice-weekly carfilzomib regimens. There is paucity of prospective studies comparing once vs. twice-weekly carfilzomib in RRMM which highlights the need for more clinical trials evaluating this regimen. Apart from efficacy and safety profile, once-weekly carfilzomib dosing also carries the potential of becoming a preferred option in terms of lesser financial burden and number of patient visits to the infusion centers. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Description: Background: The utility of bone marrow biopsy (BMB) in patients with Hodgkin lymphoma (HL) has been a controversial topic. Clinical stage 4 (CS4) has been shown to be an independent poor prognostic marker and is also included in the International Prognostic Scoring (IPS) index for predicting both progression-free survival (PFS) and overall survival (OS). The current guidelines still recommend performing a BMB in patients with stage IIB (with unfavorable risk factors), III and IV HL, mainly for staging purposes. Though bone marrow involvement (BMI) upstages the HL to stage IV, the prognostic significance of BMI remains unclear. The study was aimed to determine the prognostic significance of BMI in underserved patients with HL and to determine the prognostic importance of other blood parameters. Methods: The study was conducted at John H. Stroger Hospital of Cook County, an inner city tertiary care hospital providing care to the underserved population of Chicago. Charts of 241 patients diagnosed with HL were screened from tumor registry. Patients with incomplete charts were not included in the study. Socio-demographic, clinical and pathologic factors were recorded at the time of diagnosis. For comparative purpose, CS4 disease did not include patients with BMI. Kaplan-Meier and bivariate analyses were performed. Cox regression analyses were conducted to explore predictors of OS and PFS. Hazard ratios (HR) with 95% confidence intervals (CI) were obtained. Results: The study included 192 patients of which 41% were Afro-Americans, 34% were Hispanics and 21% were Caucasians. Median age was 34 years with 25.5% patients being older than 45 years and 68% patients being women. Seventeen percent patients were positive for HIV. Nodular sclerosis was the most common histologic subtype (55%), bulky disease was recorded in 19% patients and 61.5% patients had B-symptoms. CS4 disease was seen in 12% patients while 28% patients were stage III, 47% were stage II and 13% were stage I. Single-site BMB was done in 96% patients. BMB was positive for involvement with HL in 19% patients (n=37). Out of these 37 patients, 84% (n=31) had advanced stage (III & IV) HL. BMI was seen in 5% patients with early-stage HL (stages I-II) and 41% patients with advanced-stage HL. Median IPS score was 2 (range 0-6). Median values for clinical factors were: hemoglobin-11.8 g/dL, platelets 314.5 x103/uL, leukocytes 8.3 x103/uL, neutrophils 6x103/uL, lymphocytes 1.2 x103/uL and albumin 3.7 g/dL. Mean OS was 143 months (95% CI 126-160) with 5-year OS of 89%. Significant correlates of OS included: age 45 years or older (HR 2.83, 95%CI 1.25-6.43, P =0.013), HIV (HR 2.80, 95%CI 1.19-6.61, P =0.019), nodular sclerosistype (HR 0.29, 95%CI 0.12-0.71, P =0.006), CS4 disease (HR 3.05, 95%CI 1.20-7.77, P =0.019), BM positive for involvement with HL (HR 5.76, 95%CI 2.56-12.98, P