PMID- 35123433 OWN - NLM STAT- MEDLINE DCOM- 20220309 LR - 20220309 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 22 IP - 1 DP - 2022 Feb 6 TI - Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia. PG - 148 LID - 10.1186/s12885-022-09256-2 [doi] LID - 148 AB - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). METHODS: A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. RESULTS: Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. CONCLUSIONS: In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy. CI - (c) 2022. The Author(s). FAU - Bourrier, Nicole AU - Bourrier N AD - Max Rady College of Medicine, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. FAU - Landego, Ivan AU - Landego I AD - Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. FAU - Bucher, Oliver AU - Bucher O AD - Department of Epidemiology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Squires, Mandy AU - Squires M AD - CancerCare Manitoba Research Institute, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Streu, Erin AU - Streu E AD - Department of Nursing, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Hibbert, Irena AU - Hibbert I AD - Department of Nursing, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Whiteside, Theresa AU - Whiteside T AD - Department of Nursing, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Gibson, Spencer B AU - Gibson SB AD - CancerCare Manitoba Research Institute, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. AD - Department of Biochemistry and Medical Genetics, Max Rady College of Medicine University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. AD - Department of Immunology, Max Rady College of Medicine University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. FAU - Geirnaert, Marc AU - Geirnaert M AD - Provincial Oncology Drug Program, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Johnston, James B AU - Johnston JB AD - Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. AD - CancerCare Manitoba Research Institute, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Dawe, David E AU - Dawe DE AD - Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. AD - CancerCare Manitoba Research Institute, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. AD - Department of Medical Oncology and Hematology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. FAU - Banerji, Versha AU - Banerji V AD - Max Rady College of Medicine, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. vbanerji@cancercare.mb.ca. AD - Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. vbanerji@cancercare.mb.ca. AD - CancerCare Manitoba Research Institute, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. vbanerji@cancercare.mb.ca. AD - Department of Biochemistry and Medical Genetics, Max Rady College of Medicine University of Manitoba, 727 McDermot Ave, Winnipeg, MB, R3E 3P5, Canada. vbanerji@cancercare.mb.ca. AD - Department of Medical Oncology and Hematology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, R3E 0V9, Canada. vbanerji@cancercare.mb.ca. LA - eng PT - Evaluation Study PT - Journal Article DEP - 20220206 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 18D0SL7309 (Chlorambucil) RN - O43472U9X8 (obinutuzumab) SB - IM MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/*administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Chlorambucil/*administration & dosage MH - Female MH - Humans MH - Injection Site Reaction/*epidemiology/etiology MH - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/mortality MH - Male MH - Manitoba MH - Middle Aged MH - Retrospective Studies MH - Treatment Outcome PMC - PMC8818183 OTO - NOTNLM OT - CLL OT - Chronic lymphocytic leukemia OT - Front-line therapy OT - Obinutuzumab OT - Retrospective cohort study COIS- The authors declare that there are no competing interests with respect to this project. EDAT- 2022/02/07 06:00 MHDA- 2022/03/11 06:00 PMCR- 2022/02/06 CRDT- 2022/02/06 20:25 PHST- 2021/06/15 00:00 [received] PHST- 2022/01/31 00:00 [accepted] PHST- 2022/02/06 20:25 [entrez] PHST- 2022/02/07 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2022/02/06 00:00 [pmc-release] AID - 10.1186/s12885-022-09256-2 [pii] AID - 9256 [pii] AID - 10.1186/s12885-022-09256-2 [doi] PST - epublish SO - BMC Cancer. 2022 Feb 6;22(1):148. doi: 10.1186/s12885-022-09256-2.