Abstracts 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Initial Therapy

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Dickran Kazandjian, Elizabeth Hill, Candis Morrison, et al.

Authors Conclusion from the Abstract: Treatment of HR-SMM with KRd-R to prevent symptomatic MM resulted in an MRD negative CR rate of 70% with a median duration of 5.5 years. At the 5-year landmark, only 10% of patients developed MM which is favorable compared to historical rates with no treatment of ~75%. Alternative approaches using monotherapy lenalidomide (Lonial et al, JCO 2019) resulted in no CRs and a 5-year progression rate of 22% with a treatment discontinuation rate of 51% compared to 7% in our study. More aggressive approaches include GEM-CESAR (Mateos et al, ASH 2019) incorporating HDM-ASCT with KRd-R. Importantly, the rate of MRD negativity reported in GEM-CESAR was 56% compared to 70% in this study. Overall, the benefit compared to risk with KRd in SMM is very favorable. Future randomized trials will be needed to lock in this conclusion.

Jonathan L. Kaufman, Jacob P. Laubach, Douglas Sborov, et al.

Authors Conclusion from the Abstract: After 26.7 months of median follow-up, the addition of DARA to RVd induction and consolidation, followed by D-R maintenance in patients with transplant-eligible NDMM continued to demonstrate deep and improved responses, including higher sCR and MRD negativity rates, compared with lenalidomide alone. Maintenance therapy increased sCR and MRD negativity rates, compared to post-consolidation rates. No new safety concerns were observed with longer follow-up.

Pieter Sonneveld,  Meral Beksac, Bronno Van Der Holt, et al.

Authors Conclusion from the Abstract: Consolidation treatment with VRD followed by continuous lenalidomide maintenance improves PFS and quality of response in NDMM as compared to maintenance alone. The rate of toxicity and second primary malignancies is acceptable. This study is registered with EudraCT number 2009-017903-28 and ClinicalTrials.gov NCT01208766, and has completed recruitment.

Thierry Facon, Christopher P. Venner, Nizar Bahlis, et al.

Authors Conclusion from the Abstract: The addition of ixazomib to Rd led to a clinically meaningful, obvious positive trend in PFS, with a 13.5-month improvement in the median in transplant-ineligible NDMM patients. Improvements in TTP and CR rate were also observed. In line with TOURMALINE-MM1 (Avet-Loiseau Blood 2017), IRd improved the poor PFS associated with expanded high-risk cytogenetics vs placebo-Rd. Safety findings were generally consistent with the well-characterized, tolerable, and manageable toxicity profile of ixazomib/IRd. IRd is a feasible treatment option for certain patients who could benefit from an all-oral triplet combination.

Raymond L. Comenzo, Efstathios Kastritis, MD, Giovanni Palladini, et al.

Authors Conclusion from the Abstract: Regardless of the criteria used, the addition of DARA to VCd increased the rates of deep hematologic responses in patients with newly diagnosed AL amyloidosis, which, in turn, was associated with prolonged MOD-PFS. These results support the benefit of DARA in this patient population.

Giovanni Palladini, Stefan Schönland, Giampaolo Merlini, et al. and Efstathios Kastritis, MD1

Authors Conclusion from the Abstract: Therapeutic options for AL amyloidosis have changed considerably over time. After 2010 CyBorD became the prominent first-line treatment; the proportion of pts not achieving a response was reduced by 23% and a trend towards improvement of OS for stage IIIA disease was observed, but the prognosis of stage IIIB pts remained dismal and early mortality remained unchanged. Early diagnosis is still an unmet need, and improved therapies are essential.