TY - JOUR
T1 - Precision Medicine Approach Based on Molecular Alterations for Patients with Relapsed or Refractory Multiple Myeloma
T2 - Results from the MM-EP1 Study
AU - Andreozzi, Fabio
AU - Dragani, Matteo
AU - Quivoron, Cyril
AU - Le Bras, Fabien
AU - Assi, Tarek
AU - Danu, Alina
AU - Belhadj, Karim
AU - Lazarovici, Julien
AU - Cotteret, Sophie
AU - Bernard, Olivier A.
AU - Ribrag, Vincent
AU - Michot, Jean Marie
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Background: Despite that cytogenetic and molecular analysis of tumor cells can rapidly identify recurring molecular abnormalities, no personalized therapy is currently available in the setting of relapsed/refractory multiple myeloma (r/r MM). Methods: MM-EP1 is a retrospective study aimed at comparing a personalized molecular-oriented (MO) versus a non-molecular-oriented (no-MO) approach in r/r MM. Actionable molecular targets and their associated therapies were the BRAF V600E mutation and BRAF inhibitors; t(11;14)(q13;q32) and BCL2 inhibitors; and t(4;14)(p16;q32) with FGFR3 fusion/rearrangements and FGFR3 inhibitors. Results: One hundred three highly pretreated r/r MM patients with a median age of 67 years (range 44–85) were included. Seventeen (17%) patients were treated using an MO approach with BRAF inhibitors (vemurafenib or dabrafenib, n = 6), BCL2 inhibitor (venetoclax, n = 9), or FGFR3 inhibitor (erdafitinib, n = 2). Eighty-six (86%) patients received non-MO therapies. Overall response rate was 65% in MO patients versus 58% in the non-MO group (p = 0.053). Median PFS and OS were 9 and 6 months (HR = 0.96; CI95 = 0.51–1.78; p = 0.88) and 26 and 28 months (HR = 0.98; CI95 = 0.46–2.12; p = 0.98), respectively, in MO and no-MO patients. Conclusion: Despite the low number of patients treated with an MO approach, this study highlights the strengths and weakness of a molecular-targeted approach for the treatment of multiple myeloma. Widespread biomolecular techniques and improvement of precision medicine treatment algorithms could improve selection for precision medicine in myeloma.
AB - Background: Despite that cytogenetic and molecular analysis of tumor cells can rapidly identify recurring molecular abnormalities, no personalized therapy is currently available in the setting of relapsed/refractory multiple myeloma (r/r MM). Methods: MM-EP1 is a retrospective study aimed at comparing a personalized molecular-oriented (MO) versus a non-molecular-oriented (no-MO) approach in r/r MM. Actionable molecular targets and their associated therapies were the BRAF V600E mutation and BRAF inhibitors; t(11;14)(q13;q32) and BCL2 inhibitors; and t(4;14)(p16;q32) with FGFR3 fusion/rearrangements and FGFR3 inhibitors. Results: One hundred three highly pretreated r/r MM patients with a median age of 67 years (range 44–85) were included. Seventeen (17%) patients were treated using an MO approach with BRAF inhibitors (vemurafenib or dabrafenib, n = 6), BCL2 inhibitor (venetoclax, n = 9), or FGFR3 inhibitor (erdafitinib, n = 2). Eighty-six (86%) patients received non-MO therapies. Overall response rate was 65% in MO patients versus 58% in the non-MO group (p = 0.053). Median PFS and OS were 9 and 6 months (HR = 0.96; CI95 = 0.51–1.78; p = 0.88) and 26 and 28 months (HR = 0.98; CI95 = 0.46–2.12; p = 0.98), respectively, in MO and no-MO patients. Conclusion: Despite the low number of patients treated with an MO approach, this study highlights the strengths and weakness of a molecular-targeted approach for the treatment of multiple myeloma. Widespread biomolecular techniques and improvement of precision medicine treatment algorithms could improve selection for precision medicine in myeloma.
KW - multiple myeloma
KW - next-generation sequencing
KW - personalized molecular therapies
UR - http://www.scopus.com/inward/record.url?scp=85149838424&partnerID=8YFLogxK
U2 - 10.3390/cancers15051508
DO - 10.3390/cancers15051508
M3 - Article
AN - SCOPUS:85149838424
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 5
M1 - 1508
ER -