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

Autoři	BACCO Di BAHLIS A MUNSHI NJ AVET-LOISEAU NC MASSZI H VITERBO T POUR Luděk GANLY L CAVO P LANGER M KUMAR C RAJKUMAR SK KEATS SV BERG JJ LIN D LI JH BADOLA B SHEN S ZHANG L ESSELTINE JC LUPTAKOVA DL DE VELDE K van RICHARDSON H MOREAU PG
Rok publikování	2020
Druh	Článek v odborném periodiku
Časopis / Zdroj	European Journal of Haematology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1111/ejh.13405
Klíčová slova	c-myc Proto-Oncogenes; multiple myeloma; mutation; progression-free survival; RNA sequencing
Popis	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 as: NCT01564537