Impact of high-dose melphalan followed by autologous stem cell transplant in producing MRD negative complete response in newly diagnosed multiple myeloma.

person Mohammad Ebraheem Mayo Clinic, Rochester, MN info_outline Mohammad Ebraheem, Joselle Cook, Shaji Kumar, Dragan Jevremovic, Angela Dispenzieri, David Dingli, Francis Buadi, Prashant Kapoor, Martha Lacy, Taxiarchis Kourelis, Rahma M. Warsame, Moritz Binder, Eli Muchtar, Suzanne R. Hayman, Ronald S. Go, Nelson Leung, S. Vincent Rajkumar, Robert A. Kyle, Wilson I. Gonsalves, Morie A. Gertz

Authors person Mohammad Ebraheem Mayo Clinic, Rochester, MN info_outline Mohammad Ebraheem, Joselle Cook, Shaji Kumar, Dragan Jevremovic, Angela Dispenzieri, David Dingli, Francis Buadi, Prashant Kapoor, Martha Lacy, Taxiarchis Kourelis, Rahma M. Warsame, Moritz Binder, Eli Muchtar, Suzanne R. Hayman, Ronald S. Go, Nelson Leung, S. Vincent Rajkumar, Robert A. Kyle, Wilson I. Gonsalves, Morie A. Gertz Organizations Mayo Clinic, Rochester, MN, Division of Hematopathology, Mayo Clinic, Rochester, MN, Division of Hematology, Mayo Clinic, Rochester, MN Abstract Disclosures Research Funding No funding received Background: High dose melphalan followed by autologous stem cell transplant (HDM-ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) despite advances in treatments. Achievement of complete response (CR) is associated with improved overall survival (OS) and progression-free survival (PFS); Minimal Residual Disease (MRD) negativity (-) using next generation flow cytometry with a sensitivity of 10 -5 is strongly associated with improved PFS and OS. We investigated the rates of conversion to MRD(-), especially MRD(-) CR following HDM-ASCT in patients with NDMM. Methods: We retrospectively reviewed patients with NDMM who underwent early HDM-ASCT at Mayo Clinic Rochester from May 2018 to July 2019. Response assessment was conducted after induction and within 100 days post-ASCT based on 2016 IMWG criteria, except for using Mass-Fix instead of immunofixation. MRD was assessed in bone marrow using the established Euro Flow protocol with sensitivity of 10 -5 . The FISH assay was used to risk-stratify patients as high-risk (HR) and standard risk (SR) cytogenetics as per the mSMART guidelines. Primary outcome measure was the conversion to MRD(-) CR after ASCT. Secondary outcomes include the overall conversion to MRD(-) irrespective of IMWG response, the impact of HR cytogenetics and pre-ASCT IMWG response on conversion to MRD(-) CR. Results: Two-hundred and ten patients were included; 126 (60%) were male and median age 62 years (range 32–77 years). There were 78 (44%) patients with HR cytogenetics. Pre-ASCT, 23 patients (11%) achieved MRD(-) CR, and 66 (31%) patients achieved MRD(-) CR post ASCT. Of 187 patients not in MRD(-) CR pre-ASCT, 45 (24%) converted to MRD(-) CR. Table provides a breakdown of the conversion rate of pre-ASCT IMWG response category to MRD(-) CR post ASCT and patients with MRD(+) CR had the highest rate (78%) of conversion. The presence of HR cytogenetics did not impact rates of MRD(-) CR achievement post ASCT irrespective of pre-ASCT IMWG response (p = 1.0). Overall, irrespective of IMWG response, 43 (20%) patients were MRD(-) pre-ASCT (19 in VGPR, 24 in CR or better) and 102 (49%) patients were MRD(-) post-ASCT (36 in VGPR, 66 in CR or better). Among 85 patients in VGPR post-ASCT, 36 were MRD(-) of which 8 (22%) progressed, while 49 were MRD(+) of which 24 (49%) progressed (p = 0.014). Conclusions: Upfront HDM-ASCT in patients with NDMM leads to deeper responses with 24% converting to MRD(-) CR and more than doubling of the total rate of MRD(-) irrespective of IMWG response. Percent conversion to MRD- CR post-ASCT by IMWG response achieved pre-ASCT. Pre-ASCT IMWG response N (%) Post-ASCT MRD (-) CR N (%) CR MRD(+) 27 (14) 21 (78) VGPR MRD(-) 20 (11) 6 (30) VGPR MRD(+) 65 (35) 13 (20) PR 59 (32) 4 (7) SD 16 (8) 1 (6)