New regimens and directions in the management of newly diagnosed multiple myeloma

Abstract

The introduction of novel agents over the last decade has rapidly expanded the therapeutic landscape of multiple myeloma (MM) for both transplant‐eligible and transplant‐ineligible patients. The assessment of minimal residual disease (MRD) by next‐generation flow cytometry or next‐generation sequencing is established as a powerful predictor of long‐term outcomes. The use of MRD in response‐adapted clinical trials may provide opportunities to identify candidates for treatment escalation and de‐escalation. Agents with proven activity in the relapsed and refractory setting are being studied in the management of high‐risk newly diagnosed MM (NDMM). Here, we summarize the most recent clinical trials that have led to the current paradigms in the management of NDMM. We also discuss how novel agents could be incorporated in the newly diagnosed setting and potential clinical trial designs that could leverage MRD information with the goal of treatment optimization.

The Effect of Belantamab Mafodotin on Primary Myeloma–Stroma Co-Cultures: Asymmetrical Mitochondrial Transfer between Myeloma Cells and Autologous Bone Marrow Stromal Cells

“…Although multiple myeloma accounts for approximately 10% of hematologic malignancies and has the second highest incidence, it is still generally considered an incurable disease. However, with the introduction of novel therapies into the standard of care in the recent decade, such as second-generation proteasome inhibitors (carfilzomib, ixazomib), third-generation immunomodulatory drugs (pomalidomide), HDAC inhibitors (panobinostat), monoclonal antibodies (daratumumab, isatuximab, elotuzumab), and the BCL-2 inhibitor venetoclax, approximately 90% of myeloma patients have a considerable chance of reaching complete remission and measurable residual disease negativity [ 4 , 29 , 30 ]. Moreover, the latest therapies including bispecific antibodies, antibody–drug conjugates, and chimeric antigen receptor T cells show promising efficacy even for multi-refractory patients with high-risk features and may help to achieve and maintain deep and highly durable responses [ 6 , 31 , 32 , 33 ].…”

“…In the past two decades, there has been a substantial breakthrough in the treatment of multiple myeloma as many new classes of drugs have been introduced for clinical care; the approval and routine clinical use of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs), followed by the availability of monoclonal antibodies (mAbs), have been fundamental breakthroughs in improving survival outcomes in patients. Nevertheless, multiple myeloma remains a largely incurable malignancy [ 3 , 4 ]. Based on the results of a study involving 14 academic centers in the US, the median overall survival (OS) of patients refractory to anti-CD38 mAb was only 8.6 months.…”

Varón de 49 años con diplopía e hipoestesia en región mandibular

“…El tratamiento de la enfermedad se basa en el trasplante autólogo de células hematopoyéticas y en el tratamiento médico conformado por un inhibidor de la proteasoma (bortezomib) junto a agentes inmunomoduladores (talidomida y lenalidomida) y corticoides (dexametasona) 7 . Aunque el pronóstico de la enfermedad es globalmente malo, la supervivencia de los pacientes ha mejorado sustancialmente en las últimas dos décadas con estos recursos terapéuticos 3 .…”

Treatment Strategy for Multiple Myeloma to Improve Immunological Environment and Maintain MRD Negativity

“…In a phase 2 trial on LEN maintenance therapy after ASCT, no relapse was noted in patients with sustained MRD negativity for two years after a median follow-up time of 40.7 months, while the PFS in patients with loss of MRD negativity was shorter than in those with persistent MRD positivity [16]. MRD status might affect decisions regarding treatment discontinuation or escalation/de-escalation of treatment intensity [117], and several response-adapted clinical trials on MRD are ongoing [118]. Thus, MRD negativity is an important prognostic factor for long-term survival and a biomarker of the treatment strategy.…”