PMID- 34083230
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20230106
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 27
IP  - 17
DP  - 2021 Sep 1
TI  - Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma 
      Treated with Venetoclax in a Phase I, First-in-Human Study.
PG  - 4690-4695
LID - 10.1158/1078-0432.CCR-20-4842 [doi]
AB  - PURPOSE: We previously reported a 44% overall response rate (ORR) with the oral 
      BCL-2 inhibitor venetoclax in a phase I study of relapsed/refractory non-Hodgkin 
      lymphoma (NHL). Complete response (CR) was observed in patients with mantle cell 
      lymphoma [(MCL), 21%, n = 6/28] and follicular lymphoma [(FL), 17%, n = 5/29], 
      and partial response (PR) noted in several patients with Waldenstrom 
      macroglobulinemia (WM), and marginal zone lymphoma (MZL). Here, we report the 
      long-term outcomes of these four cohorts. PATIENTS AND METHODS: All patients (n = 
      106) received venetoclax monotherapy in dose cohorts of 200 to 1,200 mg daily 
      until disease progression or unacceptable toxicity. ORR, progression-free 
      survival (PFS), duration of response (DoR), and adverse events (AEs) were 
      evaluated. RESULTS: At a median follow-up of 38.5 months (range, 30.0-46.5), the 
      median PFS for all 106 patients was 5.4 [95% confidence interval (CI), 3.5-8.4] 
      months (FL, 10.8; MCL, 11.3; MZL, 21.2; and WM, 30.4). The median DoR was 14.9 
      (95% CI, 9.7-27.6) months (FL, 26.6; MCL, 15.7; MZL, 20.1; and WM, 25.3). 
      Achievement of CR versus PR predicted longer DoR in both MCL (31.5 vs. 10.1 
      months) and FL (37.6 vs. 9.7 months). All grade hematologic AEs were infrequent: 
      neutropenia (19%), anemia (19%), and thrombocytopenia (17%), with no new 
      cytopenias after 2 years on therapy. Nonhematologic AEs included nausea (49%), 
      diarrhea (46%), fatigue (44%), with decreased incidence after 1 year. 
      CONCLUSIONS: Venetoclax monotherapy has a manageable safety profile and achieves 
      durable responses in a subset of patients with FL, MCL, WM, and MZL, particularly 
      in those who achieve CR. Further research is warranted on combination strategies 
      to enhance the durability of response to venetoclax.
CI  - (c)2021 The Authors; Published by the American Association for Cancer Research.
FAU - Davids, Matthew S
AU  - Davids MS
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachuetts. matthew_davids@dfci.harvard.edu.
FAU - Roberts, Andrew W
AU  - Roberts AW
AUID- ORCID: 0000-0002-7341-5720
AD  - Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne 
      Hospital, Melbourne, Australia.
AD  - Department of Medical Biology, University of Melbourne, and Walter and Eliza Hall 
      Institute, Melbourne, Australia.
FAU - Kenkre, Vaishalee P
AU  - Kenkre VP
AD  - Division of Hematology and Medical Oncology, University of Wisconsin School of 
      Medicine and Public Health, Madison, Wisconsin.
FAU - Wierda, William G
AU  - Wierda WG
AD  - Department of Leukemia, MD Anderson Cancer Center, Houston, Texas.
FAU - Kumar, Abhijeet
AU  - Kumar A
AD  - Division of Hematology and Oncology, University of Arizona Cancer Center, Tuscon, 
      Arizona.
FAU - Kipps, Thomas J
AU  - Kipps TJ
AD  - Division of Hematology-Oncology, Department of Medicine, University of California 
      San Diego Moores Cancer Center, San Diego, California.
FAU - Boyer, Michelle
AU  - Boyer M
AD  - F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom.
FAU - Salem, Ahmed Hamed
AU  - Salem AH
AUID- ORCID: 0000-0002-9261-1583
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Pesko, John C
AU  - Pesko JC
AUID- ORCID: 0000-0002-7568-7762
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Arzt, Jennifer A
AU  - Arzt JA
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Mantas, Margaret
AU  - Mantas M
AUID- ORCID: 0000-0003-2829-2757
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Kim, Su Y
AU  - Kim SY
AUID- ORCID: 0000-0001-8059-0482
AD  - AbbVie Inc., North Chicago, Illinois.
FAU - Seymour, John F
AU  - Seymour JF
AUID- ORCID: 0000-0003-2188-6835
AD  - Department of Haematology, Peter MacCallum Cancer Centre and Royal Melbourne 
      Hospital, Melbourne, Australia.
AD  - Department of Medical Biology, University of Melbourne, and Walter and Eliza Hall 
      Institute, Melbourne, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT01328626
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210603
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Sulfonamides)
RN  - N54AIC43PW (venetoclax)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Bridged Bicyclo Compounds, Heterocyclic/*therapeutic use
MH  - Follow-Up Studies
MH  - Humans
MH  - Lymphoma, B-Cell, Marginal Zone/*drug therapy
MH  - Lymphoma, Follicular/*drug therapy
MH  - Lymphoma, Mantle-Cell/*drug therapy
MH  - Recurrence
MH  - Sulfonamides/*therapeutic use
MH  - Time Factors
MH  - Waldenstrom Macroglobulinemia/*drug therapy
PMC - PMC9401543
EDAT- 2021/06/05 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/08/24
CRDT- 2021/06/04 06:05
PHST- 2020/12/16 00:00 [received]
PHST- 2021/03/29 00:00 [revised]
PHST- 2021/05/27 00:00 [accepted]
PHST- 2021/06/05 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2021/06/04 06:05 [entrez]
PHST- 2022/08/24 00:00 [pmc-release]
AID - 1078-0432.CCR-20-4842 [pii]
AID - CCR-20-4842 [pii]
AID - 10.1158/1078-0432.CCR-20-4842 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2021 Sep 1;27(17):4690-4695. doi: 10.1158/1078-0432.CCR-20-4842. 
      Epub 2021 Jun 3.