Precision Medicine Approach Based on Molecular Alterations for Patients with Relapsed or Refractory Multiple Myeloma: Results from the MM-EP1 Study.

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, = 6), BCL2 inhibitor (venetoclax, = 9), or FGFR3 inhibitor (erdafitinib, = 2). Eighty-six (86%) patients received non-MO therapies. Overall response rate was 65% in MO patients versus 58% in the non-MO group ( = 0.053). Median PFS and OS were 9 and 6 months (HR = 0.96; CI95 = 0.51-1.78; = 0.88) and 26 and 28 months (HR = 0.98; CI95 = 0.46-2.12; = 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.