PMID- 35750419
OWN - NLM
STAT- MEDLINE
DCOM- 20220628
LR  - 20220716
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 10
IP  - 6
DP  - 2022 Jun
TI  - Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: 
      modest activity and cases of hyperprogression.
LID - 10.1136/jitc-2022-004984 [doi]
LID - e004984
AB  - Peripheral T-cell lymphomas (PTCL), a heterogeneous group of mature aggressive 
      non-Hodgkin's lymphomas, carry a worse prognosis for most subtypes when compared 
      with their B-cell counterparts. Despite recent approval of newer therapies, the 
      outlook for patients with relapsed/refractory (RR) PTCL remains poor and new 
      treatment strategies are clearly needed. Targeting the profoundly 
      immunosuppressive tumor microenvironment in PTCL is one such approach. To 
      determine whether immune checkpoint blockade targeting program death receptor 1 
      would be effective in PTCL, we conducted an investigator-initiated phase 2 
      prospective study of single-agent nivolumab for RR PTCL. We report here results 
      of the pre-specified interim analysis. METHODS: The primary objective was to 
      assess the overall response rate (ORR). Secondary objectives were to assess 
      safety and tolerability of nivolumab in PTCL and to assess progression-free 
      survival (PFS), duration of response (DOR) and overall survival (OS). 
      Hyperprogressive disease (HPD) was defined as time-to-treatment failure of less 
      than or equal to one month from initiation of therapy. RESULTS: Twelve patients 
      who received at least one cycle of nivolumab were included in this interim 
      analysis. Half (6/12) of the patients had angioimmunoblastic T-cell lymphoma 
      (AITL), 3/12 had PTCL, not otherwise specified. Most (11/12) were advanced stage, 
      had extranodal disease (97.1%) and had received a prior autologous stem cell 
      transplant (50%). The ORR was 33% (95% CI: 12.3 to 63.7%) with two complete 
      response and two partial response. The median PFS was however short at 2.7 months 
      (95% CI: 1.5 to NE); and the median OS was 6.7 months (95% CI: 3.4 to NE). The 
      median DOR was also short at 3.6 months (95% CI: 1.9 to NE). HPD occurred in four 
      patients, three of whom had AITL. Observed grade 3 and higher adverse events 
      (AEs) were non-hematologic in 5/12 (42%), while hematologic AEs were seen in 3/12 
      (25%). CONCLUSIONS: Nivolumab had modest clinical activity in R/R PTCL. Due to a 
      high number of hyperprogression and short DOR, a decision was made to halt the 
      study. These findings likely reflect the distinct biology of PTCL and should be 
      considered when designing future studies using checkpoint inhibitors in these 
      diseases. TRIAL REGISTRATION NUMBER: NCT03075553.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Bennani, N Nora
AU  - Bennani NN
AUID- ORCID: 0000-0001-8358-5953
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA Bennani.Nora@mayo.edu.
FAU - Kim, Hyo Jin
AU  - Kim HJ
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA.
FAU - Pederson, Levi D
AU  - Pederson LD
AD  - Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
FAU - Atherton, Pamela J
AU  - Atherton PJ
AD  - Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
FAU - Micallef, Ivana N
AU  - Micallef IN
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA.
FAU - Thanarajasingam, Gita
AU  - Thanarajasingam G
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA.
FAU - Nowakowski, Grzegorz S
AU  - Nowakowski GS
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA.
FAU - Witzig, Thomas
AU  - Witzig T
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA.
FAU - Feldman, Andrew L
AU  - Feldman AL
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Ansell, Stephen M
AU  - Ansell SM
AD  - Division of Hematology, Mayo Clinic, Rochester, MN, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03075553
PT  - Clinical Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Disease Progression
MH  - Humans
MH  - *Lymphoma, T-Cell, Peripheral/drug therapy/pathology
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Nivolumab/pharmacology/therapeutic use
MH  - Prognosis
MH  - Prospective Studies
MH  - Tumor Microenvironment
PMC - PMC9234908
OTO - NOTNLM
OT  - Clinical Trials, Phase II as Topic
OT  - Hematologic Neoplasms
OT  - Immunotherapy
OT  - Programmed Cell Death 1 Receptor
COIS- Competing interests: None declared.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/29 06:00
PMCR- 2022/06/23
CRDT- 2022/06/24 21:06
PHST- 2022/05/19 00:00 [accepted]
PHST- 2022/06/24 21:06 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/29 06:00 [medline]
PHST- 2022/06/23 00:00 [pmc-release]
AID - jitc-2022-004984 [pii]
AID - 10.1136/jitc-2022-004984 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2022 Jun;10(6):e004984. doi: 10.1136/jitc-2022-004984.