PMID- 33563894
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20210806
IS  - 2044-5385 (Electronic)
IS  - 2044-5385 (Linking)
VI  - 11
IP  - 2
DP  - 2021 Feb 5
TI  - Phase 1 open-label study of panobinostat, lenalidomide, 
      bortezomib + dexamethasone in relapsed and relapsed/refractory multiple myeloma.
PG  - 20
LID - 10.1038/s41408-021-00407-5 [doi]
LID - 20
AB  - Additional therapeutic options are needed for relapsed and refractory multiple 
      myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation 
      study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 
      50-77]) and a median of four prior regimens (range: 2-14); 85% had refractory 
      disease (lenalidomide [80%]; bortezomib [75%]; lenalidomide and bortezomib 
      [50%]). Patients received a median of six cycles (range: 1-74) of panobinostat 
      (10 or 15 mg), lenalidomide 15 mg, bortezomib 1 mg/m(2), and dexamethasone 20 mg 
      (pano-RVd). Median follow-up was ~14 months. Six dose-limiting toxicities were 
      reported (mostly hematological); maximum tolerated dose of panobinostat (primary 
      endpoint) was 10 mg. Most common adverse events (AEs) were diarrhea (60%) and 
      peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of 
      patients and included decreased neutrophil (45%), platelet (25%) and white blood 
      cell (25%) counts, anemia (25%) and hypophosphatemia (25%). No treatment-related 
      discontinuations or mortality occurred. In evaluable patients (n = 18), overall 
      response rate was 44%, and clinical benefit rate was 61%. Median duration of 
      response was 9.2 months; progression-free survival was 7.4 months; overall 
      survival was not reached. Pano-RVd proved generally well-tolerated and 
      demonstrated potential to overcome lenalidomide and/or bortezomib resistance.
FAU - Laubach, Jacob P
AU  - Laubach JP
AUID- ORCID: 0000-0001-7565-2052
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 
      JacobP_Laubach@DFCI.HARVARD.EDU.
FAU - Tuchman, Sascha A
AU  - Tuchman SA
AUID- ORCID: 0000-0003-2109-1573
AD  - University of North Carolina, Chapel Hill, NC, USA.
FAU - Rosenblatt, Jacalyn M
AU  - Rosenblatt JM
AD  - Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
FAU - Mitsiades, Constantine S
AU  - Mitsiades CS
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
FAU - Colson, Kathleen
AU  - Colson K
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
FAU - Masone, Kelly
AU  - Masone K
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
FAU - Warren, Diane
AU  - Warren D
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
FAU - Redd, Robert A
AU  - Redd RA
AUID- ORCID: 0000-0002-1329-5288
AD  - Dana-Farber Cancer Institute, Department of Data Sciences, Boston, MA, USA.
FAU - Grayson, Dena
AU  - Grayson D
AUID- ORCID: 0000-0003-2818-8458
AD  - Secura Bio, Inc, San Diego, CA, USA.
FAU - Richardson, Paul G
AU  - Richardson PG
AUID- ORCID: 0000-0002-7426-8865
AD  - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210205
PL  - United States
TA  - Blood Cancer J
JT  - Blood cancer journal
JID - 101568469
RN  - 69G8BD63PP (Bortezomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9647FM7Y3Z (Panobinostat)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Bortezomib/administration & dosage/adverse effects/*therapeutic use
MH  - Dexamethasone/administration & dosage/adverse effects/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Lenalidomide/administration & dosage/adverse effects/*therapeutic use
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Panobinostat/administration & dosage/adverse effects/*therapeutic use
PMC - PMC7873303
COIS- J.P.L., J.M.R., K.C., K.M., D.W., and R.A.R. report no conflicts of interest. 
      S.A.T. reports grants and personal fees from Celgene, grants and personal fees 
      from Karyopharm, grants and personal fees from Sanofi, personal fees from Caelum, 
      grants from Amgen, and grants from Janssen, outside the submitted work. C.S.M. 
      discloses employment of a relative with Takeda; consultant/honoraria from Fate 
      Therapeutics, Ionis Pharmaceuticals; past research funding from Novartis; as well 
      as research funding outside the scope of this submitted work from Janssen/Johnson 
      & Johnson, TEVA, EMD Serono, AbbVie, Karyopharm, Sanofi, and Arch Oncology. D.G. 
      is a consultant to Secura Bio, Inc. P.G.R. reports grants from BMS, grants and 
      honoraria (advisory committee member) from Oncopeptides, Celgene, Takeda, and 
      Karyopharm; and honoraria (advisory committee member) from Janssen, Sanofi, and 
      Secura Bio, Inc. outside the submitted work.
EDAT- 2021/02/11 06:00
MHDA- 2021/08/07 06:00
PMCR- 2021/02/05
CRDT- 2021/02/10 05:47
PHST- 2020/07/21 00:00 [received]
PHST- 2020/12/23 00:00 [accepted]
PHST- 2020/12/08 00:00 [revised]
PHST- 2021/02/10 05:47 [entrez]
PHST- 2021/02/11 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2021/02/05 00:00 [pmc-release]
AID - 10.1038/s41408-021-00407-5 [pii]
AID - 407 [pii]
AID - 10.1038/s41408-021-00407-5 [doi]
PST - epublish
SO  - Blood Cancer J. 2021 Feb 5;11(2):20. doi: 10.1038/s41408-021-00407-5.