title: Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group.
abstract: Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.|Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Winqvist
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.|Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Asklid
authors.affiliation: Department of Hematology, South Älvsborg Hospital, Borås, Sweden.
authors.forename: P O
authors.initials: PO
authors.lastname: Andersson
authors.affiliation: Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Karlsson
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.|Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Karlsson
authors.affiliation: Department of Hematology, Sunderby Hospital, Sunderbyn Luleå, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lauri
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.|Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Lundin
authors.affiliation: Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mattsson
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Norin
authors.affiliation: Department of Hematology, Linköping University Hospital, Linköping, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Sandstedt
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden lotta.hansson@karolinska.se.|Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Hansson
authors.affiliation: Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.|Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Österborg
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D057176:Compassionate Use Trials; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010880:Piperidines; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment; D012189:Retrospective Studies; D013548:Sweden; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine