Oral Abstract Session - Session Chairs: Michael O’Dwyer
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OAB-023 - Efficacy and safety of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with progressive multiple myeloma after 1–3 prior lines of therapy: Initial results from CARTITUDE-2
Adam Cohen, Mounzer Agha, Deepu Madduri, et al.
Conclusion: Early and deep responses with manageable safety were demonstrated after a single cilta-cel infusion at the recommended phase 2 dose. Updated findings will inform suitability of outpatient treatment for this study and for the CARTITUDE-2 and CARTITUDE-4 studies.
OAB-024 - Updated results from CARTITUDE-1: Ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T (CAR-T) cell therapy, in relapsed/refractory multiple myeloma (RRMM)
Sundar Jagannath, Jesus G. Berdeja, Andrzej Jakubowiak, et al.
Conclusions: At a median follow-up of 18 mos, a single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated pts with RRMM, with manageable safety. Cilta-cel is being investigated in other MM populations in earlier lines of therapy and in outpatient settings.
OAB-025 - Talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D)×CD3 bispecific antibody, in relapsed/refractory multiple myeloma (RRMM): Updated results of a phase 1, first-in-human study
Niels W.C.J. van de Donk, Amrita Krishnan, A Oriol, et al.
Conclusions: Talquetamab, at the RP2D of 405 μg/kg SC weekly, demonstrated a high clinical response rate and was well-tolerated in pts with RRMM. Based on pharmacokinetic data, other SC dosing strategies are being explored. The promising efficacy, safety profile and convenience of SC dosing support monotherapy development and combination approaches with this novel agent.
Watch Niels van de Donk's comment on VJHEMONC - The Video Journal of Hematological Oncology:
OAB-026 - MagnetisMM-1 study of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA) targeted CD3-engaging bispecific molecule, for patients (pts) with relapsed or refractory multiple myeloma (MM)
Bhagirathbhai Dholaria, Nizar Bahlis, Noopur Raje, et al.
Conclusions: Elranatamab achieved confirmed ORR of 83% at RP2D with a manageable safety profile for pts with relapsed or refractory MM. These results confirm the feasibility and potential of BCMA-directed immunotherapy for malignant plasma cell disorders, and support further development of elranatamab for pts with MM. This study was sponsored by Pfizer.
OAB-027 - Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, for the treatment of patients with relapsed and refractory multiple myeloma (RRMM): updated results from KarMMa
Larry D. Anderson, Jr, Nina Shah, Sundar Jagannath, et al.
Conclusion: Updated results from the KarMMa trial continue to demonstrate durable and deep responses with ide-cel in heavily pretreated, triple-class–exposed pts with RRMM. Efficacy and safety data are consistent with prior reports and support a favorable clinical benefit–risk profile for ide-cel across the target dose levels.
Watch Saad Usmani's comment on VJHEMONC - The Video Journal of Hematological Oncology:
Watch Philippe Moreau's comment on VJHEMONC - The Video Journal of Hematological Oncology:
Watch Jesús San Miguel's comment on VJHEMONC - The Video Journal of Hematological Oncology:
Oral Abstract Session - Session Chairs: Ruth De Tute/Aurore Perrot/Tomas Jelinek
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OAB-028 - FAM46C-Dependent Tuning of Endoplasmic Reticulum Capacity in Multiple Myeloma
Enrico Milan, Elena Riva, Chiara Fucci, et al.
Conclusions: We infer that PCs have the ability to sense FAM46C-induced ER expansion and modulate SRP composition to minimize translational pausing and maximize Ab manufacture. This novel integrated network offers a framework to identify unprecedented highly specific therapeutic targets against PC dyscrasias.
OAB-029 - Bone marrow adipocytes induce metabolic reprogramming of multiple myeloma cells
Cristina Panaroni, Keertik Fulzele, Tomoaki Mori, et al.
NO CONCLUSION AVAILABLE
OAB-030 - Combined targeting of distinct c-Myc and JunB transcriptional programs induces synergistic anti-myeloma activity
Judith Lind, Sonia Vallet, Karoline Kollmann, et al.
Conclusions: In summary, our data demonstrate for the first time the existence of non-overlapping cMyc and JunB-regulated transcriptional programs providing the rationale for combined cMyc:JunB targeting strategies for MM therapy.
OAB-031 - Circular RNA protein tyrosine kinase 2 promotes cell proliferation, migration and suppresses apoptosis via activating microRNA-638 mediated MEK/ERK, WNT/β-catenin signaling pathways in myeloma
Fan Zhou, Haimin chen
Conclusions: circ-PTK2 promotes cell proliferation, migration, suppresses cell apoptosis via miR-638 mediated MEK&ERK and WNT&β-catenin signaling pathways in MM.
OAB-032 - Targeting GCK in RAS-mutant multiple myeloma offer a promising therapeutic approach
Shirong Li, Jing Fu, Jun Yang, et al.
Conclusions: Taken together, our data demonstrated that GCK inhibition induces cell growth inhibition and triggers apoptosis especially in RASmut MM cells. Importantly, GCK inhibition downregulates IKZF1 via a CRBN-independent mechanism. Our findings thus provide a rationale for the clinical evaluation of targeting GCK in RASmut MM patients and further mechanistic insight into the role of GCK in MM tumorigenesis as well as drug resistance.
OAB-033 - Loss-of-function of GABARAP drives tumor resistance to bortezomib-induced immunogenic cell death in multiple myeloma
Annamaria Gulla, Eugenio Morelli, Mehmet K Samur, et al.
Conclusions: Our study demonstrates that loss- of-function of GABARAP, particularly in HR patients with 17p deletion, contributes to tumor immune evasion and ICD resistance. These studies provide the framework for novel combination treatments to restore anti-MM immunity and improve patient outcome in HR MM.