Recent Development in the Journal

Thalidomide Therapy and Deep Venous Thrombosis in Multiple Myeloma

Identifying 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA and Treatment Response in Multiple Myeloma with a Multi-Step Machine Learning Approach

Mass Cytometry Identifies Immunomic Shifts in the Bone Marrow Microenvironment of Multiple Myeloma and Light Chain Amyloidosis after Standard of Care First Line Therapies

Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Accelerated immune aging after induction therapy in multiple myeloma revealed by donor-referenced immune age modeling

Bortezomib in Combination with Dexamethasone and Pegylated Liposomal Doxorubicin (DoVeD) Breaks Plateau Responses Following Initial Induction Therapy in Multiple Myeloma: Results of a Phase II Pilot Study.

Response Adapted Induction Therapy for Multiple Myeloma

Daratumumab (DARA) Maintenance Therapy Improves Depth of Response and Results in Durable Progression-Free Survival (PFS) Following Dara Plus Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) Induction Therapy in Multiple Myeloma (MM): Update of the Lyra Study

Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma Benefits Patients with Persistent Disease and Results in a High Rate of Residual Disease Clearance

Bortezomib-based regimens are widely used as induction therapy for multiple myeloma (MM). Unlike lenalidomide, the role of bortezomib in consolidation and maintenance therapy for MM is less clear. We performed a meta-analysis to evaluate the impact of bortezomib-based consolidation and maintenance therapy on survival outcomes and adverse events. PubMed, Web of Science, Embase databases, and major conference proceedings were searched for randomized controlled trials (RCTs) of bortezomib-based regimens as consolidation or maintenance therapy for MM. Ten RCTs enrolling 3147 patients were included in the meta-analysis. Bortezomib-based regimens were compared with regimens without bortezomib or observation. The meta-analysis suggested that bortezomib-based maintenance therapy improved progression-free survival (PFS; hazard ratio [HR] = 0.72, 95% CI 0.55–0.95, P = 0.02) and overall survival (OS; HR = 0.71, 95% CI 0.58–0.87, P = 0.001). Bortezomib-based consolidation therapy improved PFS (HR = 0.77, 95% CI 0.68–0.88, P < 0.001) but not OS (HR = 0.98, 95% CI 0.78–1.24, P = 0.87). Bortezomib-based consolidation/maintenance therapy led to a trend toward increased risk of grade ≥ 3 neurologic symptoms, gastrointestinal symptoms, and fatigue. More research is warranted to further assess the role of bortezomib-based consolidation and maintenance therapy for multiple myeloma.

8035 Background: LYRA is a community practice-based, phase 2, single-arm study (NCT02951819) evaluating DARA + CyBorD as an immunomodulatory drug-sparing regimen in MM. The primary analysis demonstrated the safety and efficacy of DARA + CyBorD in newly diagnosed MM (NDMM) and relapsed MM (RMM), and an update showed that DARA maintenance therapy deepened responses. We present the final end-of-study analysis of LYRA. Methods: US pts aged ≥18 years with MM per IMWG criteria and ≤1 prior line of therapy received 4-8 induction cycles of DARA + CyBorD (cyclophosphamide 300 mg/m2 PO weekly [QW]; bortezomib 1.5 mg/m2 SC on Days [D] 1, 8, and 15; dexamethasone 40 mg PO or IV QW every 28 days; DARA IV 8 mg/kg on D1 and D2 of cycle [C]1, 16 mg/kg QW C1D8-C2, 16 mg/kg Q2W C3-6, and 16 mg/kg Q4W C7-8). After induction, eligible pts could receive autologous stem cell transplantation (ASCT). Pts received up to 12 maintenance cycles with DARA 16 mg/kg IV Q4W and were followed for up to 36 months after induction. Results: In total, 101 (NDMM, n = 87; RMM, n = 14) pts were enrolled; 36% of pts had high-risk cytogenetics. NDMM and RMM pts received a median of 6 and 8 induction cycles, respectively. Among NDMM pts, 44.8% (39/87) underwent ASCT and 72.4% (63/87) completed 12 months of maintenance. Rates of ≥VGPR and ≥CR were 82.1% and 48.7% in NDMM pts who underwent ASCT, and 70.2% and 29.8% in NDMM pts who did not (Table). With a median follow-up of 35.7 months, median progression-free survival (PFS) and overall survival (OS) were not reached for NDMM pts. Estimated 36-month PFS rates were 69.3% and 72.6% for NDMM pts who did and did not receive ASCT, respectively; estimated 36-month OS rates were 94.9% and 84.3% (Table). Among RMM pts, 7.1% (1/14) underwent ASCT and 50.0% (7/14) completed 12 months of maintenance; efficacy outcomes are shown in the Table. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 62.0% of all pts, with the most common (≥10%) being neutropenia (14.0%). Serious TEAEs occurred in 33.0% of pts, the most common being pneumonia (4.0%) and pulmonary embolism (3.0%). TEAEs led to death in 2.0% of pts, all unrelated to study treatment. Infusion-related reactions occurred in 56.0% of pts; the majority were mild (4.0% of pts had grade 3/4 events). Conclusions: DARA used for induction with CyBorD and maintenance as monotherapy resulted in durable, deep responses in pts with NDMM or RMM, with a 3-year PFS rate of 70% in NDMM irrespective of ASCT status. With longer follow-up, no new safety concerns were identified. Clinical trial information: NCT02951819. [Table: see text]

This work established and validated a radiomics-driven framework to quantify therapeutic response in multiple myeloma (MM). By leveraging CT-based Delta features, we aimed to delineate sub-visual temporal changes and assess their incremental predictive value beyond conventional clinical biomarkers. We retrospectively evaluated 131 newly diagnosed MM patients (April 2019-November 2024), partitioned into training and validation cohorts (7:3 ratio). Baseline and post-induction CT images (mean interval: 132days), reconstructed via high-resolution sharp kernels, served as the basis for analysis. Following a rigorous inter-observer stability filter (ICC > 0.90), Delta-radiomic features were extracted from the ribs, manubrium, and thoracic spine. A stability-first selection pipeline, utilizing mRMR and LASSO regression, identified the most robust signatures for model construction. ISS staging (I/II/III: 19.9%/29.0%/51.1%) was balanced across cohorts. The multi-regional radiomics signature (RadDeltaAll) demonstrated superior stability compared to single-site models. In the training set, the integrated framework yielded an AUC of 0.855. In the independent validation cohort, while single-site performance varied, the comprehensive RadDeltaAll model maintained high diagnostic stability . AUC=0.842. Notably, the clinical biomarker 24hU-Pro was retained as a "biological anchor"; although it did not statistically enhance predictive accuracy, it provided essential context for systemic renal burden without compromising model integrity. CT-based Delta radiomics constitutes a robust, non-invasive biomarker for MM response assessment. While 24hU-Pro serves as an indispensable biological reference, the multi-regional radiomic signature remains the primary engine of predictive power. This underscores the clinical necessity of quantitative, skeleton-aware analysis in steering individualized induction therapy. MM: Multiple myeloma; CT: Computed tomography; ROI: Region of interest; AUC: Area under the curve; ESM: Electronic supplementary material; WBLDCT: Whole-body low-dose computed tomography; IMWG: International Myeloma Working Group; LASSO: Least Absolute Shrinkage and Selection Operator; mRMR: minimum Redundancy Maximum Relevance; SVM: Support Vector Machine; RF: Random Forest; XGBoost: Extreme Gradient Boosting; GLCM: Gray-Level Co-occurrence Matrix; GLRLM: Gray-Level Run-Length Matrix; GLSZM: Gray-Level Size Zone Matrix; NGTDM: Neighboring Gray-Tone Difference Matrix; DSC: Dice Similarity Coefficient; DCA: Decision Curve Analysis.

Lenalidomide, bortezomib, and dexamethasone (RVd) has emerged as a preferred induction therapy in multiple myeloma (MM) in the United States. Due to lenalidomide's teratogenic risk, patients and prescribers must comply with a risk evaluation and mitigation strategy (REMS) program. The REMS program limits dispensing to certain third-party specialty pharmacies, whose average prescription fill times are longer than in-house specialty pharmacies. In practice, a delay in procurement of lenalidomide may mean that patients start therapy with only bortezomib and dexamethasone, delaying the start of more effective triplet therapy. The primary objective of this study is to determine if a delay from start of bortezomib and dexamethasone to start of triplet therapy with lenalidomide impacts rate of achievement of very good partial response (VGPR) after four cycles of RVd. This was a single-center retrospective review of adults with newly diagnosed MM who received RVd induction therapy at University of North Carolina Medical Center between April 2014 and June 2017. Patients who started lenalidomide ≥10 days after bortezomib comprised the "Delay" group, while those who started lenalidomide concurrently with bortezomib or within 1-9 days after bortezomib comprised the "No Delay" group. The primary outcome was VGPR or better response rate after four cycles of RVd. Thirty-eight patients met inclusion criteria. Nine patients (23.7%) experienced any delay in initiation of lenalidomide, with a mean delay of 7.8 days (range 1-18). Four patients (10.5%) experienced a delay ≥10 days. No patients in the Delay group were of reproductive potential, compared to 8.8% in the No Delay group (p = 0.54). VGPR or better response rate did not differ between the Delay and No Delay groups (66.7% vs. 58.8%, p = 0.79). The mean number of lenalidomide prescriptions generated per RVd cycle was 1.35 (range 1-5, SD 0.74). This study did not demonstrate an effect on clinical response after delays ≥10 days between bortezomib and lenalidomide initiation. No patients in the delay group were females of reproductive potential, which is the primary target for increased safety behind the REMS program.

Multiple myeloma (MM) is considered to be an essentially incurable haematological malignant disease, probably because of the existence of resistant clonal precursor cell with self-renewal capacity. Recent data have indicated that the myeloma cell hierarchy includes circulating clonal memory B cells, which differ considerably from the classical end-stage plasma cells, infiltrating the bone marrow. The pathophysiological significance of these cells is unknown, but hypothetically they may serve as 'sleeping' myeloma stem cells responsible for and 'feeding' post-treatment relapse and progression. The present study evaluates the toxicity and feasibility of fludarabine, added to the VAD-induction regimen in MM, and investigates the effect on the myeloma cell hierarchy. Nineteen patients were randomised to receive either four cycles of VAD (n = 9) or two cycles of VAD, followed by two cycles of VAD combined with 5 days fludarabine 25 mg/m2/day i.v. (n = 10). Toxicity evaluation showed more profound neutropenia in the fludarabine-treated patients and two infectious episodes in each study arm: three were fever of unknown origin while one, in the fludarabine-arm, was a local skin infection at the insertion site of the central venous line. Nine of the fludarabine-treated patients responded to treatment (two complete remission, seven partial remission), compared with five responders (all PR) in the control-arm. The effects on the blood circulating myeloma compartments identified an increased reduction of CD19+ B cells and myeloma plasma cells in the fludarabine-arm. In conclusion, adding fludarabine to VAD induction in multiple myeloma is feasible and may be clinically effective by reducing the myeloma clone.

Bortezomib with HIG-Dose Dexamethasone as First Line Therapy in Patients with Multiple Myeloma Candidates to High-Dose Therapy.