For people newly diagnosed with multiple myeloma, the news is especially tough when the cancer has already spread outside the bone marrow—a condition called extramedullary disease. This makes treatment more difficult and the outlook less certain. A recent trial tested a new approach: adding a drug called selinexor to the standard three-drug combination (bortezomib, lenalidomide, and dexamethasone). The goal was to see if this four-drug combo could effectively attack this aggressive form of the disease. The trial involved 29 treated patients. The results were encouraging. Nearly 90% of patients responded to the treatment, with over half achieving a stringent complete response—a deep level of remission where no cancer is detectable by the most sensitive tests. Importantly, imaging scans showed the cancer outside the bone marrow shrank or disappeared in nearly 90% of patients, with complete resolution in about 80%. After one year, about 88% of patients were alive without their cancer getting worse, and over 96% were still alive. The treatment had side effects, with serious ones occurring in about 37% of patients, including low platelet counts and pneumonia, but no deaths were related to the treatment. The manageable side effects allowed over half of the participants to proceed to a stem cell transplant, a potentially curative step. These early findings suggest this four-drug combination is a rational and promising first-line option for patients facing this aggressive myeloma, supporting the need for larger, randomized studies to confirm its benefits.
SVRD yields 89.7% ORR, 79.3% EMD resolution in NDMM with EMD in phase 2 trialCan a new drug combination help people with aggressive multiple myeloma? Early results show promise
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This multicenter, open-label, single-arm, phase 2, investigator-initiated trial evaluated the efficacy and safety of selinexor combined with bortezomib, lenalidomide, and dexamethasone (SVRD) in newly diagnosed multiple myeloma (NDMM) with extramedullary disease (EMD). Between 17 October 2022 and 27 November 2025, 30 patients were enrolled, with 29 treated patients forming the modified intention-to-treat (mITT) and safety populations (median age, 60 years). Induction consisted of four 28-day SVRD cycles, followed by protocol-specified consolidation/maintenance and optional autologous stem cell transplantation (ASCT). The primary endpoint was the best overall response rate (ORR) during induction per International Myeloma Working Group criteria, with patients lacking a postbaseline assessment imputed as nonresponders. In the mITT cohort, the ORR was 89.7%, comprising stringent complete response (58.6%), complete response (3.4%), very good partial response (10.3%), and partial response (17.2%). Imaging documented EMD regression in 89.7% of patients, with complete resolution in 79.3% and partial resolution in 10.3%. The 12-month progression-free survival and overall survival rates were 87.9% and 96.3%, respectively; median survival endpoints were not reached (median follow-up, 18 months). High-risk cytogenetics were present in 31.0% of patients, and 27.6% met ultra-high-risk (double-hit) criteria. Grade ≥3 treatment-emergent adverse events occurred in 37.3% of patients, most commonly thrombocytopenia (24.1%), neutropenia (6.9%), and pneumonia (10.3%); no treatment-related deaths were reported. The regimen enabled ASCT in 51.7% of participants. The authors conclude SVRD produced deep hematologic responses and high EMD clearance with manageable toxicity, supporting it as a rational frontline option for EMD-positive NDMM and justifying randomized studies to confirm durability and benchmark it against contemporary quadruplets and cellular therapies.