Chr t(14;16)

P1, N=20, Completed, Noah Merin | Active, not recruiting --> Completed | N=30 --> 20 | Trial completion date: Nov 2031 --> Nov 2024

P1/2, N=70, Active, not recruiting, Wake Forest University Health Sciences | Trial completion date: Oct 2024 --> Nov 2032 | Trial primary completion date: Oct 2024 --> Apr 2029

P2, N=52, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting

Early recognition and prompt intervention are essential in managing MM patients, especially in those with high-risk cytogenetic abnormalities. This case serves as a reminder for clinicians to maintain a high index of suspicion for MM, even in younger populations, when presented with unexplained kidney injury.

P2, N=29, Active, not recruiting, Emory University | Trial completion date: Aug 2024 --> Mar 2026 | Trial primary completion date: Jul 2024 --> Mar 2025

P1/2, N=20, Active, not recruiting, Ciusss de L'Est de l'Île de Montréal | Trial primary completion date: Sep 2021 --> Oct 2023

P3, N=1087, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Nov 2023 --> Nov 2025

CD34+ stem cells (SC) mobilization was performed with cyclophosphamide (2-4 g/smq) and G-CSF in 26 patients (74%) after a median time of 28 days (range: 13-50 221 Posters days) from the end of induction; 3 (11%) patients were mobilized only with G-CSF. Plerixafor on demand was administered in 13 pts (50%) failing to achieve the desired collection target...Hematological toxicity was the most common adverse event (50%; G≥3 anemia, neutropenia, thrombocytopenia occurred in 8%, 17% and 8% respectively), followed by infections (33%) and PNP (25%). In our real-life experience, D-VTD regimen was proven effective and well tolerated in TE-NDMM patients.

A novel NGS targeted panel was designed and successfully validated, whose main novelty resides in the possibility to call CNAs from off-target reads, that can be used to define MM pts’ genomic risk factors, possibly required in the daily clinical practice. Thanks to AIRC IG2018-22059, AILBolognaODV.

P2, N=194, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: May 2025 --> Sep 2025

P3, N=534, Recruiting, Sanofi | Trial completion date: Oct 2026 --> Feb 2027

34 pts (81%) underwent SC collection, all with plerixafor (median yield 8.91x106 CD34+/kg). Extended frontline Dara-KRd for NDMM without ASCT induced high rates of sCR and/or MRD(-) within 8 cycles, meeting the primary endpoint. The rate and depth of MRD(-) improved beyond C8. This ASCT-free approach led to lower PFS for pts with 2+ HRCA, as also seen with ASCT, but excellent PFS in those with standard-risk disease and 1 HRCA.

Key exclusion criteria included prior ixazomib exposure, refractoriness to anti-CD38 therapy, and refractoriness to bortezomib or carfilzomib therapy at last exposure. Treatment with DVd followed by DId with a PI iCT from bortezomib to ixazomib is a feasible approach for continuous PI and anti-CD38 therapy, leading to durable responses in RRMM pts, among whom nearly all (97%) were lenalidomide refractory. Immune correlates revealed distinct patterns of T-cell and NK-cell phenotypes when profiled serially in responding and non-responding pts. Additional correlative analyses are ongoing.

ConclusionsIn the largest scRNA-seq study on CTCs to date, we demonstrate the utility of CTC-based molecular profiling for prognostication of patients with early-stage disease and provide novel insights into PC circulatory potential. Additional analyses are ongoing to gain further insight into intra-patient CTC heterogeneity and define high-risk disease CTC signatures that emerge throughout the MM disease continuum.

Briefly, pts with RRMM who have received ≥3 prior lines of therapy were enrolled & received a single infusion of CART-ddBCMA following lymphodepletion chemotherapy (fludarabine: 30 mg/m2/d & cyclophosphamide: 300 mg/m2/d daily for 3 days). Adverse events with CART-ddBCMA, including CRS & ICANS, were manageable & no off-tumor tissue-targeted toxicity, delayed neurotoxicity, or Parkinsonian-like events were observed in the entire cohort at the time of data-cut. Ongoing efficacy results are encouraging, with 100% ORR, including 35 (92%) response of VGPR or better & 29 (76%) with CR/sCR. More importantly, clinical responses were durable with an overall estimated 18-mo PFS rate of 67% with comparable clinical responses seen in 'high-risk' patients known to have poor prognosis.

Several studies have shown reduced efficacy of both FDA approved BCMA targeted chimeric antigen receptor T cell therapies (CAR-T) for myeloma, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), when administered after BCMA targeted bi-specific antibodies...Tocilizumab was administered to 4 (18%) pts... This single center study in patients with heavily pretreated and prior BCMA-TT demonstrated favorable ORR (63%) and CR (36%) rates, comparable to pts in the MajesTEC-1 trial, without prior BCMA-TT exposure. No new safety signals were identified. Results on progression free survival (PFS) and overall survival (OS) will be reported with continued follow up and will be presented in the meeting.

Finally, focusing on patients' response to 1st line therapy stratification, loss of miR-221/222 could efficiently define optimal (sCR/CR/VGPR) and poor (PR/SD/PD) responders' subgroups (PFS: p<0.001, OS: p<0.001; Fig.2E,F). In conclusion, we identified miR-221/222 loss in CD138+ plasma cells as a powerful independent predictor of patients' risk for disease progression and poor treatment outcome, while miR-221/222-fitted multivariate prognostic models resulted to improved patients' risk-stratification and prediction of MM treatment outcome.

Lenalidomide has shown to delay progression in patients with high-risk smoldering multiple myeloma (HR-SMM) and curative intent trials with carfilzomib-based therapy and stem cell transplantation have been recently reported in HR-SMM leading to deep responses but with concern for treatment-related toxicities...Treatment with D-RVD is 2 years (24 cycles) with daratumumab subcutaneous (SQ) per standard dose and schedule, bortezomib 1.3mg/m2 SQ on days 1, 8, 15 for cycles 1-6 then biweekly until completion of cycle 24, lenalidomide 25mg on days 1-21 for cycles 1-6 followed by 15mg d1-21 from cycles 7-24 with weekly low dose dexamethasone... D-RVD in HR-SMM demonstrates significant activity, including a 100% ORR and high rates of MRD-negative disease, preventing progression to overt myeloma.

In conclusion, CTCs are detectable in about 33% of pts with asymptomatic monoclonal gammopathies, both in MGUS (in 17%) and more frequently in SMM (in 42%) pts. Their presence is associated with a trend towards increased risk of progression to symptomatic disease for SMM, but needs longer follow up to identify the role of CTCs in MGUS and the additive information over available risk stratification tools, which could provide an non-invasive, easy-to-follow longitudinally biomarker.

In the ongoing phase 1/2 CC-220-MM-001 study, iberdomide plus dexamethasone had a favorable safety profile and demonstrated clinically meaningful activity in triple-class refractory multiple myeloma (MM) patients, including those refractory to lenalidomide and pomalidomide (IMiDs®)...All patients received a PI/IMiD-containing induction regimen which also included daratumumab in 41% of patients...Iberdomide represents a novel effective post-ASCT maintenance strategy with a favorable safety profile and superior response improvement at 6 months than what has been observed with lenalidomide maintenance (26% at 6 months in the EMN02 study). Additional follow-up is needed to define the recommended maintenance dose that will be used in the randomized phase 3 EXCALIBER maintenance study, which will evaluate iberdomide vs. lenalidomide maintenance post-ASCT.

P2, N=40, Completed, Maisonneuve-Rosemont Hospital | Active, not recruiting --> Completed

P2, N=52, Recruiting, Academic and Community Cancer Research United | Trial primary completion date: Dec 2023 --> Sep 2024

P2; Trial primary completion date: Aug 2023 --> Jul 2024

P2, N=194, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2023 --> Mar 2025

Here we present first real world data demonstrating Ven to be an effective MM treatment option in heavily pretreated MM patients.

Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months.

The results of this study indicate that in the diagnostic work-up of MM, MFC may help to identify different patient subsets and improve risk stratification. These observations need to be validated in larger series of patients with a longer follow-up.

Compared with qualitative analysis, FF value was independently associated with HRMM. The quantitative features of diffuse marrow infiltration on MRI scans are more effective in detecting HRMM.

In conclusion, although one of the cyclins D is overexpressed at the mRNA level in almost all MM patients, in approximately half of the patients this does not translate into detectable protein. This suggests that cyclins D could not play an oncogenic role in a proportion of patients with MM.

P2, N=12, Terminated, Hackensack Meridian Health | Active, not recruiting --> Terminated; FDA Hold Due to Updated Risks

Our results suggest that Dara-CVRd induction and extended post-ASCT Dara-VRd consolidation markedly improve PFS for UHiR NDMM patients over conventional management, supporting further evaluation of this strategy.

P2, N=34, Recruiting, Emory University | Trial completion date: Oct 2024 --> Oct 2025

P1, N=30, Active, not recruiting, Noah Merin | Trial completion date: May 2024 --> Nov 2031

P2, N=83, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

P1, N=2, Terminated, Rutgers, The State University of New Jersey | Trial completion date: Nov 2023 --> Sep 2022 | Active, not recruiting --> Terminated; Lack of enrollment

No superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post-transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment.

P2, N=50, Recruiting, Sun Yat-sen University | Trial completion date: Sep 2022 --> Dec 2025 | Trial primary completion date: Sep 2022 --> Dec 2025

P2, N=244, Recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2025 --> May 2025

P2, N=30, Not yet recruiting, PETHEMA Foundation

In this heavily pretreated population, belamaf was associated with an ORR of 47% and the PFS and OS were 4.0 and 8.4 months, respectively. Our results are in keeping with data from the DREAMM-2 trial and real-world studies and support belamaf as an option in the relapsed/refractory setting with careful management of ocular toxicity.