PMID- 34589671
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211008
IS  - 2572-9241 (Electronic)
IS  - 2572-9241 (Linking)
VI  - 5
IP  - 10
DP  - 2021 Oct
TI  - The mTOR Inhibitor Temsirolimus Added to Rituximab Combined With Dexamethasone, 
      Cytarabine, and Cisplatinum (R-DHAP) for the Treatment of Patients With Relapsed 
      or Refractory DLBCL - Results From the Phase-II STORM Trial.
PG  - e636
LID - 10.1097/HS9.0000000000000636 [doi]
LID - e636
AB  - There is a high need for novel treatment options in relapsed and refractory 
      diffuse large B-cell lymphoma. Single agent mammalian target of rapamycin (mTOR) 
      inhibitor treatment has shown promising efficacy in this entity. Here, we report 
      on the results of the mTOR-inhibitor temsirolimus combined to standard 
      rituximab-DHAP salvage regimen in a prospective, multicenter, phase II, 
      open-label study. The STORM regimen consisted of rituximab 375 mg/m(2) (day 2) 
      and DHAP (dexamethasone 40 mg day 3-6, cisplatinum 100 mg/m(2) day 3, cytarabine 
      2 x 2  g/m(2) day 4) with temsirolimus added on day 1 and 8 of a 21-day cycle, 
      with 2 to 4 cycles planned. In part I, dose levels of 25, 50, 75, and 100 mg for 
      temsirolimus were predefined. Based on the observed toxicity profile, a 
      temsirolimus dose of 25 mg was defined as recommended dose for the part II 
      extension cohort of the trial. The intention-to-treat cohort comprised 53 
      patients. Median age was 63 years and median number of prior regimen was 1. All 
      but 1 patient had prior rituximab exposure. Temsirolimus dose was 50 mg on day 1 
      and 8 in 6 patients from the part I of the trial and 25 mg in the remaining 47 
      patients. In general, treatment was well tolerated with leucopenia and 
      thrombocytopenia as most frequent severe adverse events. The overall response 
      rate after the last cycle of temsirolimus R-DHAP was 66% with 24% complete 
      responses. The ability to mobilize stem cells was not impaired by the treatment 
      regimen. Twenty-eight patients received consolidation treatment with high-dose 
      therapy (HDT) and stem cell transplantation. Median duration of response was not 
      reached. The total 2-year progression-free survival (PFS) and overall survival 
      (OS) were 53% and 59%. Patients who were consolidated with HDT achieved a 2-year 
      PFS and a 2-year OS of 77.8% and 82.1%, respectively. We conclude that 
      temsirolimus can be safely added to rituximab and DHAP with promising activity.
CI  - Copyright (c) 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the European Hematology Association.
FAU - Witzens-Harig, Mathias
AU  - Witzens-Harig M
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Germany.
FAU - Viardot, Andreas
AU  - Viardot A
AD  - Department of Internal Medicine III, University Hospital Ulm, Germany.
FAU - Keller, Ulrich
AU  - Keller U
AD  - III. Medical Department of Hematology and Medical Oncology, Technical University 
      of Munich, Germany.
FAU - Wosniok, Julia
AU  - Wosniok J
AD  - Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center of 
      the Johannes Gutenberg-University, Mainz, Germany.
FAU - Deuster, Oliver
AU  - Deuster O
AD  - Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center of 
      the Johannes Gutenberg-University, Mainz, Germany.
FAU - Klemmer, Jennifer
AU  - Klemmer J
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Germany.
FAU - Geueke, Anne-Marie
AU  - Geueke AM
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Germany.
FAU - Meissner, Julia
AU  - Meissner J
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Germany.
FAU - Ho, Anthony D
AU  - Ho AD
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Germany.
FAU - Atta, Johannes
AU  - Atta J
AD  - Department of Hematology and Oncology, University of Frankfurt Hospital, Germany.
FAU - Marks, Reinhard
AU  - Marks R
AD  - Department of Hematology/Oncology and Stem Cell Transplantation, University 
      Medical Center, Freiburg, Germany.
FAU - La Rosee, Paul
AU  - La Rosee P
AD  - Department of Hematology and Oncology, University Hospital of Jena, Germany.
FAU - Buske, Christian
AU  - Buske C
AD  - Institute of Experimental Tumor Research and Department of Internal Medicine III, 
      University of Ulm, Germany.
FAU - Dreyling, Martin H
AU  - Dreyling MH
AD  - Department of Internal Medicine III, Ludwig-Maximilians University of Munich, 
      Germany.
FAU - Hess, Georg
AU  - Hess G
AD  - Department of Internal Medicine III (Hematology, Oncology, Pneumology), 
      University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
LA  - eng
PT  - Journal Article
DEP - 20210923
PL  - United States
TA  - Hemasphere
JT  - HemaSphere
JID - 101740619
PMC - PMC8476051
EDAT- 2021/10/01 06:00
MHDA- 2021/10/01 06:01
PMCR- 2021/09/23
CRDT- 2021/09/30 07:20
PHST- 2021/04/02 00:00 [received]
PHST- 2021/08/03 00:00 [accepted]
PHST- 2021/09/30 07:20 [entrez]
PHST- 2021/10/01 06:00 [pubmed]
PHST- 2021/10/01 06:01 [medline]
PHST- 2021/09/23 00:00 [pmc-release]
AID - 10.1097/HS9.0000000000000636 [doi]
PST - epublish
SO  - Hemasphere. 2021 Sep 23;5(10):e636. doi: 10.1097/HS9.0000000000000636. 
      eCollection 2021 Oct.