TY - JOUR
TI - Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study
AU - Dreyling, M.
AU - Santoro, A.
AU - Mollica, L.
AU - Leppä, S.
AU - Follows, G.
AU - Lenz, G.
AU - Kim, W.S.
AU - Nagler, A.
AU - Dimou, M.
AU - Demeter, J.
AU - Özcan, M.
AU - Kosinova, M.
AU - Bouabdallah, K.
AU - Morschhauser, F.
AU - Stevens, D.A.
AU - Trevarthen, D.
AU - Munoz, J.
AU - Rodrigues, L.
AU - Hiemeyer, F.
AU - Miriyala, A.
AU - Garcia-Vargas, J.
AU - Childs, B.H.
AU - Zinzani, P.L.
JO - American Journal of Hematology
PY - 2020
VL - 95
TODO - 4
SP - 362-371
PB - John Wiley and Sons Inc
SN - 0361-8609, 1096-8652
TODO - 10.1002/ajh.25711
TODO - alanine aminotransferase;  alkylating agent;  antineoplastic agent;  aspartate aminotransferase;  copanlisib;  rituximab;  copanlisib;  pyrimidine derivative;  quinazoline derivative, abdominal pain;  adult;  afferent loop syndrome;  aged;  alanine aminotransferase blood level;  anemia;  Article;  aspartate aminotransferase blood level;  autologous hematopoietic stem cell transplantation;  backache;  bronchitis;  cancer patient;  cancer recurrence;  cancer survival;  cholecystitis;  chronic lymphatic leukemia;  colitis;  constipation;  controlled study;  coughing;  decreased appetite;  diarrhea;  diffuse large B cell lymphoma;  disease exacerbation;  disease severity;  disorientation;  drug efficacy;  drug megadose;  drug response;  drug safety;  fatigue;  female;  fever;  follicular lymphoma;  follow up;  Gram negative sepsis;  histopathology;  human;  hyperglycemia;  hypertension;  hypertransaminasemia;  incidence;  Klebsiella infection;  long term care;  lung embolism;  lymphocytic lymphoma;  lymphoma;  lymphoplasmacytoid lymphoma;  major clinical study;  male;  marginal zone lymphoma;  multiple cycle treatment;  neutropenia;  objective response rate;  overall survival;  pneumonia;  progression free survival;  refractory indolent lymphoma;  sepsis;  side effect;  thrombocytopenia;  upper respiratory tract infection;  vomiting;  Waldenstroem macroglobulinemia;  adverse event;  allograft;  autotransplantation;  B cell lymphoma;  diarrhea;  drug administration;  hematopoietic stem cell transplantation;  hyperglycemia;  hypertension;  middle aged;  multicenter study (topic);  multimodality cancer therapy;  neutropenia;  phase 2 clinical trial (topic);  salvage therapy;  survival analysis;  treatment outcome;  very elderly, Adult;  Aged;  Aged, 80 and over;  Allografts;  Antineoplastic Combined Chemotherapy Protocols;  Clinical Trials, Phase II as Topic;  Combined Modality Therapy;  Diarrhea;  Drug Administration Schedule;  Female;  Follow-Up Studies;  Hematopoietic Stem Cell Transplantation;  Humans;  Hyperglycemia;  Hypertension;  Lymphoma, B-Cell;  Male;  Middle Aged;  Multicenter Studies as Topic;  Neutropenia;  Phosphoinositide-3 Kinase Inhibitors;  Progression-Free Survival;  Pyrimidines;  Quinazolines;  Salvage Therapy;  Survival Analysis;  Transplantation, Autologous;  Treatment Outcome
TODO - Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors. © 2019 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.
ER -