Oral Abstract Session - Session Chairs: Jens Hillengass/Angelo Maiolino
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OAB-034 - Evaluating the Impact of Cytogenetic Abnormalities on Treatment Outcomes in Patients with AL Amyloidosis: Subanalyses From the ANDROMEDA Study
Shaji Kumar, Angela Dispenzieri, Divaya Bhutani, et al.
Conclusion: Consistent with the primary analysis of ANDROMEDA, subgroup analyses showed the benefit of D-VCd vs VCd, irrespective of cytogenetic abnormalities. Rates of deep hematologic response were not impacted by t(11;14) and amp1q21 in patients treated with D-VCd, but were generally lower in VCd-treated patients with t(11;14) and amp1q21. These findings further support the use of D-VCd as standard of care in pts with newly diagnosed AL amyloidosis, regardless of cytogenetic abnormalities.
OAB-035 - Minimally invasive profiling of tumor and immune cells to stratify risk in smoldering multiple myeloma (SMM): the iMMunocell study
Rosalinda Termini, David Zihala, Cirino Botta, et al.
Conclusions: This is the first study performing CTC and immune monitoring every 6 months in PB samples from patients with SMM. Our results suggest that CTC numbers have greater prognostic value than BM PC counts, and that a new 0.7/2/20 model could be dynamically assessed to identify SMM patients at risk of developing active MM. Beyond CTC numbers,this study is also uncovering key immune cell types associated with disease progression.
OAB-036 - Graded Renal Response Criteria and Revised Renal Progression Criteria for Light chain (AL) Amyloidosis
Eli Muchtar, Brendan Wisniowski, Giovanni Palladini, et al.
Conclusions: We validated new graded renal response criteria based on reduction in 24-h proteinuria. These 4-level renal response criteria highlight the importance of achieving a deep renal response to improve renal and overall survival. These findings will allow clinicians to make decision on therapy changes or augmentation based on response depth as early as 6-month before irreversible renal failure has developed.
OAB-037 - Assessing the prognostic utility of the Mayo 2018 and IMWG 2020 smoldering multiple myeloma risk stratification scores applied post diagnosis
Alissa Visram, S. Vincent Rajkumar, Prashant Kapoor, et al.
Conclusion: Our findings support the use of the Mayo 2018 and IMWG 2020 scores post- diagnosis. We showed that patients migrating to a higher risk category have an increased risk of progression, suggesting that patients evolving to a high-risk score during follow-up should be considered for early intervention treatment approaches.
Watch Maria-Victoria Mateos' & Irene Ghobrial's comment on VJHEMONC - The Video Journal of Hematological Oncology:
Precursor conditions: management of smoldering myeloma
OAB-038 - Graded Cardiac Response Criteria for AL Amyloidosis: The Impact of Depth of Cardiac Response on Survival
Eli Muchtar, Angela Dispenzieri, Brendan Wisniowski, et al.
Conclusions: We validated the prognostic value of graded cardiac response. These response criteria allow better discrimination of patient populations and assessment of treatment effectiveness in an era of improved therapies for AL amyloidosis. The study emphasizes the importance of early diagnosis which increases the likelihood of deep and durable cardiac responses.
Oral Abstract Session - Session Chairs: Constantine Mitsiades/Virgina Abello
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OAB-039 - Distinct immunoglobulin heavy-chain variable gene repertoire and its clinical relevance in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma
Yuting Yan, Jun Wang, Wenjie Xiong, et al.
Conclusion: WM/LPL appears to be composed of different subgroups based on the IGHV repertoire. The mutational status and the IGHV CDR3 length indicated the role for antigen selection in WM/LPL development. The presence of IGHV4 genes proved to be a potential risk factor associated with outcome which deserved further study.
OAB-040 - Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström Macroglobulinemia
Sabrin Tahri, Tarek Mouhieddine, Robert Redd, et al.
Conclusion: We demonstrate that CH is common in WM patients and is associated with increased risk of progression from precursor states but not with inferior survival. Further work is needed to determine how the presence of CH might promote progression to WM and whether it can be incorporated into future risk stratification models. Importantly, our data do not support changes in clinical management or alterations in therapy for patients with WM and coexistent CH and reinforce the need to interpret NGS results within their specific clinical context.
OAB-041 - Epithelial-mesenchymal-transition regulated by Junctional Adhesion Molecule-A (JAM-A) associates with aggressive extramedullary multiple myeloma disease.
Antonio Solimando, Matteo Da Vià, Giorgio Croci, et al.
Conclusions: Collectively, these data reveal JAM-A-mediated signaling critical for EMT transition and invasive behavior. Based on these findings we propose JAM-A as a promising biomarker and novel theragnostic target in MM patients.
OAB-042 - Targeting Free Light Chain Secretion via Botulinum Neurotoxin is a Novel Therapeutic Strategy in AL amyloidosis by Inducing a Terminal Unfolded Protein Response
MARIA MOSCVIN, Tianzeng Chen, Peter Czarnecki, et al.
Conclusions: We show that cytotoxic BoNTs block FLC secretion, trigger a terminal UPR and induce apoptosis in AL and MM models. We provide proof of concept that targeting FLC secretion has a potential clinical translatability.
OAB-043 - Progression and probability of progression are driven by different genomic features in precursor conditions in myeloma
Anil Aktas-Samur, Mariateresa Fulciniti, Sanika Derebail, et al.
Conclusions: In conclusion, our results now provide the basis to develop genomic definition of SMM as well as risk driving features.
OAB-044 - Anti-CD38 nanobodies as theranostic agents for multiple myeloma
Elodie Duray, Margaux Lejeune, Mireille Dumoulin, Matthias D'Huyvetter, Jo Caers
Conclusions: In conclusion, this is the first report on CD38-binding Nbs used for the identification and treatment of MM cells by conjugating them to diagnostic and therapeutic isotopes.
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OAB-045 - COVID-19 Vaccine Responsiveness in Patients with Multiple Myeloma and Waldenström Macroglobulinemia
Andrew Branagan, Matthew Lei, Andrew J. Yee, et al.
Conclusions: These preliminary data suggest impaired serologic responses following COVID- 19 vaccines in patients with both MM and WM. Overall, WM patients showed more severe impairment of COVID-19 S antibody responses. Most previously untreated WM patients achieved S antibody responses, however suboptimal antibody responses were seen in WM patients who received rituximab within 12 months or on active BTK inhibitors. In MM patients, being in disease remission associated with improved S antibody response. Vaccination among MM and WM patients with MRNA-1273 elicited significantly higher S antibody response rates in comparison to other vaccines. Complete serologic responses including neutralization and T-cell studies are pending and will be updated. Further understanding of the immunological response to COVID19 vaccination is needed to clarify patients risks, and necessity for booster or alternative protective measures against COVID-19.
OAB-046 - COVID-19 infection in multiple myeloma patients – retrospective analysis of 371 Czech patients
Jakub Radocha, Ivan Špička, Luděk Pour, et al.
Conclusions: The mortality of MM patients with COVID-19 was very high (20.8%). Healthcare utilization was high with almost half of the infected myeloma patients needing inpatient treatment. No apparent risk factors in terms of disease status or previous treatment were identified.
OAB-047 - Plasma cell disorder patients are left vulnerable after one dose of the BNT162b2 mRNA or the ChAdOx-nCOV-19 COVID-19 vaccines
Wei Yee Chan, Lara Howells, William Wilson, et al.
Conclusion: Serologic response to SARS-CoV- 2 vaccination is lower in PCD patients than reported healthy controls at 68% after one dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. Nearly a third do not respond to a single vaccine dose causing concerns that PCD patients are left vulnerable with a delayed vaccination strategy and should be prioritised to receiving the second dose at the recommended manufacturers time scale of 3 or 4 weeks.
OAB-048 - Suboptimal humoral immune response to SARS- CoV-2 mRNA vaccination in myeloma patients is associated with anti-CD38 mAb and BCMA- targeted treatment.
Oliver Van Oekelen, Sarita Agte, Charles Gleason, et al.
Conclusion: MM patients mount a suboptimal IgG response after SARS-CoV-2 vaccination with 15.8% developing no detectable anti-S IgG. Ongoing analyses will show kinetics of patients with low-normal Ab levels in comparison to healthy controls. SARS-CoV-2-specific T cell responses and extensive immunophenotyping of >40 patients in the context of vaccination will be reported at the meeting. Immediate implications are the continuation of non-pharmacological interventions, e.g. masking and social distancing, for vulnerable patients. The findings underscore a need for serological monitoring of MM patients following COVID-19 vaccination and for clinical trials assessing use of prophylactic strategies or studies exploring additional immunization strategies.
OAB-049 - Poor Post-vaccination Anti-SARS-CoV-2- Antibody Response in Patients with Multiple Myeloma correlates with low CD19+ B- lymphocyte count and Anti-CD38 Treatment
Susanne Ghandili, Martin Schönlein, Marc Lütgehetmann, et al.
Conclusion: Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination. Since both low CD19+ B lymphocyte count and CD38-directed therapy negatively impact vaccination response, booster vaccination seems therefore of utter importance.
Watch Noopur Raje's comment on VJHEMONC - The Video Journal of Hematological Oncology: