c‐MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide‐dexamethasone in myeloma

Objectives In the TOURMALINE‐MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib‐lenalidomide‐dexamethasone (IRd) showed different magnitudes of progression‐free survival (PFS) benefit vs placebo‐Rd according to number and type of prior therapies, with greater benefit seen in patient...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:European journal of haematology Ročník 105; číslo 1; s. 35 - 46
Hlavní autori: Di Bacco, Alessandra, Bahlis, Nizar J., Munshi, Nikhil C., Avet‐Loiseau, Hervé, Masszi, Tamás, Viterbo, Luísa, Pour, Ludek, Ganly, Peter, Cavo, Michele, Langer, Christian, Kumar, Shaji K., Rajkumar, S. Vincent, Keats, Jonathan J., Berg, Deborah, Lin, Jianchang, Li, Bin, Badola, Sunita, Shen, Lei, Zhang, Jacob, Esseltine, Dixie‐Lee, Luptakova, Katarina, Velde, Helgi, Richardson, Paul G., Moreau, Philippe
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Wiley Subscription Services, Inc 01.07.2020
John Wiley and Sons Inc
Predmet:
CD19 antigen
CD81 antigen
c‐myc Proto‐Oncogenes
Dexamethasone
Immunotherapy
Multiple myeloma
mutation
Myc protein
Original
Phenotypes
progression‐free survival
Ribonucleic acid
RNA
RNA sequencing
Stem cell transplantation
Targeted cancer therapy
Tumors
RNA sequencing
mutation
c-myc Proto-Oncogenes
multiple myeloma
progression-free survival
ISSN:0902-4441, 1600-0609, 1600-0609
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:Objectives In the TOURMALINE‐MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib‐lenalidomide‐dexamethasone (IRd) showed different magnitudes of progression‐free survival (PFS) benefit vs placebo‐Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT). Methods RNA sequencing data were used to investigate the basis of these differences. Results The PFS benefit of IRd vs placebo‐Rd was greater in patients with tumors expressing high c‐MYC levels (median not reached vs 11.3 months; hazard ratio [HR] 0.42; 95% CI, 0.26, 0.66; P < .001) compared with in those expressing low c‐MYC levels (median 20.6 vs 16.6 months; HR 0.75; 95% CI, 0.42, 1.2). Expression of c‐MYC in tumors varied based on the number and type of prior therapy received, with the lowest levels observed in tumors of patients who had received 1 prior line of therapy including SCT. These tumors also had higher expression levels of CD19 and CD81. Conclusions PFS analyses suggest that lenalidomide and ixazomib target tumors with different levels of c‐MYC, CD19, and CD81 expression, thus providing a potential rationale for the differential benefits observed in the TOURMALINE‐MM1 study. This trial was registered at www.clinicaltrials.gov as: NCT01564537
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Affiliation at the time that the work was conducted: Katarina Luptakova, Tesaro, Waltham, MA, USA; Helgi van de Velde, Sanofi, Cambridge, MA, USA.
ISSN:0902-4441
1600-0609
1600-0609
DOI:10.1111/ejh.13405