Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II
Hematology Disease Topics & Pathways:
Diseases, multiple myeloma, Technology and Procedures, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant, serologic tests
Methods: Newly diagnosed MM patients failing (<partial remission [PR] as best response) front-line bortezomib-based induction therapy were enrolled onto the Australasian Leukaemia and Lymphoma Group (ALLG) MM17 trial (ACTRN12615000934549) evaluating an intensive salvage approach utilising a combination of carfilzomib, thalidomide and dexamethasone (KTd) as re-induction (KTd x 6 cycles) and as post autologous stem cell transplantation (ASCT) consolidation (KTd x 2 cycles followed by Td x10 cycles). NGF MRD status was determined pre-ASCT, post-ASCT and post-KTd consolidation utilising the standardised 8-colour EuroFlow platform. Matched serum samples from the 3 time-points were evaluated in parallel with QIP and FLC MS. Briefly, polyclonal antibodies (anti-IgG, -IgA, -IgM, -total κ, -total λ, free κ and free λ) covalently attached to paramagnetic microparticles were incubated with serum, washed and treated to simultaneously elute and reduce patient immunoglobulins. Light chain mass spectra were generated on a MALDI-TOF-MS system. Concordance between NGF and MS was assessed via the derivation of Cohen’s kappa values.
Results: Fifty patients were enrolled onto the ALLG MM17 trial. QIP and/or FLC MS identified the serum monoclonal paraprotein (PP) at baseline in all cases (100% sensitivity). Serum samples for MS with matched BM for NGF were available on 33 patients pre-ASCT, 32 post-ASCT and 26 post-KTd consolidation (91 matched samples in total). Sequential MS demonstrated serological complete remission (disappearance of MS baseline detectable monoclonal intact immunoglobulin [PP] and/or FLC) (CRMS) in 11%, 47% and 53% of patients pre-ASCT, post-ASCT and post-KTd, respectively. NGF MRD negativity at the same time points was 39%, 52% and 71% (the latter equivalent to a 50% MRD negativity rate within the original n=50 intention-to-treat population). The Cohen’s kappa values for the 3 time-points were 0.21, 0.18 and 0.35 indicating fair to moderate concordance with the best concordance at the post-KTd consolidation time-point and with a Cohen’s kappa value for the entire cohort (n=91) of 0.30. The sequential MS demonstrated that 12 patients had discordant disappearance of baseline PP and free light chains (FLC) prior to achieving CRMS. In 11 the FLC disappeared before the PP and in 1 the PP prior to the FLC. The former though to be due to either the FLC falling below the sensitivity of the technique following successful therapy or the presence of 2 sub-clones with differential drug sensitivity, whereas the latter was likely secondary to the persistence of a FLC expressing sub-clone. Post-KTd MS demonstrated good concordance with serological response (Cohen’s kappa value = 0.61) but with 18% of patients demonstrating sCR/CR despite persisting MS detectable PP and/or FLC.
Conclusion: These preliminary data confirm the utility of QIP MS and FLC MS for the sequential monitoring of tumour burden in HR MM. Concordance with standard monitoring was good with MS detectable disease in some patients with serological sCR/CR consistent with the higher sensitivity of MS. Concordance with NGF was only fair to moderate mandating the future comparison of larger sample sets to better understand the relationship between the 2 methodologies.
Disclosures: Spencer: Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Secura Bio: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Specialised Therapeutics Australia: Consultancy, Honoraria. Khong: Novartis Oncology: Research Funding; Alfred Hospital/Monash University: Employment. Quach: Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Other: Free drug for investigator-initiated study, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: investigator initiated clinical study; Grant, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Other: investigator initiated clinical study; Grant, Research Funding; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kalff: Amgen: Honoraria; Celgene: Honoraria; pfizer: Honoraria. Reynolds: Novartis Australia: Honoraria; Alfred Health: Employment, Other: Biostatistician for trials funded by the Australian government and Abbvie, Amgen, Celgene, GSK, Janssen-Cilag, Merck, Novartis, Takeda, but sponsored by Alfred Health.; AUSTRALASIAN LEUKAEMIA & LYMPHOMA GROUP (ALLG): Consultancy; Novartis AG: Equity Ownership.
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