PMID- 35946431
OWN - NLM
STAT- MEDLINE
DCOM- 20221215
LR  - 20221215
IS  - 1099-1069 (Electronic)
IS  - 0278-0232 (Linking)
VI  - 40
IP  - 5
DP  - 2022 Dec
TI  - A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory 
      multiple myeloma patients.
PG  - 906-913
LID - 10.1002/hon.3066 [doi]
AB  - Ruxolitinib with lenalidomide and dexamethasone shows anti-myeloma effects in 
      vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma (MM) 
      cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore 
      sensitivity to lenalidomide. A phase I trial was conducted to determine the 
      safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for 
      patients with relapsed/refractory (RR)MM who had been treated with lenalidomide, 
      steroids and a proteasome inhibitor and showed progressive disease at study 
      entry. A traditional 3 + 3 dose escalation design was used to enroll subjects in 
      four cohorts. Subjects received ruxolitinib twice daily, lenalidomide daily on 
      days 1-21 of a 28 day cycle and methylprednisolone orally every other day. 
      Primary endpoints were safety, clinical benefit rate (CBR) and overall response 
      rate (ORR). Forty-nine patients were enrolled. The median age was 64 years and 
      they had received a median of six prior treatments including lenalidomide and 
      steroids to which 94% were refractory. No dose limiting toxicities occurred. The 
      CBR and ORR were 49% and 36%, respectively. All responding patients were 
      refractory to lenalidomide. Grade 3 or 4 adverse events (AEs) included anemia 
      (17%), decreased lymphocyte count (15%), and hypophosphatemia (10%). Most common 
      serious AEs included sepsis (9.8%) and pneumonia (7.8%). This Phase I trial 
      demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to 
      lenalidomide and steroids for patients with RRMM. These results represent a 
      promising novel therapeutic approach for treating MM. NCT03110822.
CI  - (c) 2022 John Wiley & Sons Ltd.
FAU - Berenson, James R
AU  - Berenson JR
AUID- ORCID: 0000-0003-1587-6104
AD  - Berenson Cancer Center, West Hollywood, Los Angeles, California, USA.
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
AD  - Institute for Myeloma and Bone Cancer Research, West Hollywood, Los Angeles, 
      California, USA.
FAU - Kim, Clara
AU  - Kim C
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
FAU - Bujarski, Sean
AU  - Bujarski S
AD  - Berenson Cancer Center, West Hollywood, Los Angeles, California, USA.
FAU - To, Jennifer
AU  - To J
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
FAU - Spektor, Tanya M
AU  - Spektor TM
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
FAU - Martinez, Daisy
AU  - Martinez D
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
FAU - Turner, Carley
AU  - Turner C
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
FAU - Ghermezi, Matthew
AU  - Ghermezi M
AD  - Oncotherapeutics, West Hollywood, Los Angeles, California, USA.
FAU - Eades, Benjamin M
AU  - Eades BM
AD  - Berenson Cancer Center, West Hollywood, Los Angeles, California, USA.
FAU - Swift, Regina A
AU  - Swift RA
AD  - Berenson Cancer Center, West Hollywood, Los Angeles, California, USA.
FAU - Schwartz, Gary
AU  - Schwartz G
AD  - Berenson Cancer Center, West Hollywood, Los Angeles, California, USA.
FAU - Eshaghian, Shahrooz
AU  - Eshaghian S
AD  - Compassionate Care Research Group, Fountain Valley, Los Angeles, California, USA.
FAU - Moss, Robert A
AU  - Moss RA
AD  - F.A.C.P., Inc, Fountain Valley, Los Angeles, California, USA.
FAU - Lim, Stephen
AU  - Lim S
AD  - Cedars-Sinai Medical Center, Los Angeles, California, USA.
FAU - Vescio, Robert
AU  - Vescio R
AD  - Cedars-Sinai Medical Center, Los Angeles, California, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03110822
GR  - 1504/Incyte Corporation/
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20220814
PL  - England
TA  - Hematol Oncol
JT  - Hematological oncology
JID - 8307268
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Humans
MH  - Middle Aged
MH  - Lenalidomide
MH  - *Multiple Myeloma/drug therapy
OTO - NOTNLM
OT  - Janus kinase inhibitors
OT  - efficacy
OT  - immunomodulation
OT  - methylprednisolone
OT  - safety
EDAT- 2022/08/11 06:00
MHDA- 2022/12/15 06:00
CRDT- 2022/08/10 05:33
PHST- 2022/07/22 00:00 [revised]
PHST- 2022/05/06 00:00 [received]
PHST- 2022/07/25 00:00 [accepted]
PHST- 2022/08/11 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/08/10 05:33 [entrez]
AID - 10.1002/hon.3066 [doi]
PST - ppublish
SO  - Hematol Oncol. 2022 Dec;40(5):906-913. doi: 10.1002/hon.3066. Epub 2022 Aug 14.