A stratified therapeutic model incorporated with studies on regulatory B cells for elderly patients with newly diagnosed multiple myeloma

Abstract

Objective Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence‐based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). Methods In this open‐label, non‐interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. Results Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) ( n = 80), lenalidomide/dexamethasone (Rd) ( n = 27), Bd with a third agent X (Bd + X) ( n = 27), and other regimens ( n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression‐free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised‐International Staging System (R‐ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs <10% ( p = 0.036) and SUVmax of PET‐CT scan >4.2 ( p = 0.000) were closely correlated with OS in the elderly MM. Conclusions For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment.

Treatment attrition rates and relevant risk factors in multiple myeloma: A real-world study in China

“…Besides, this study revealed a distinct difference in the attrition rates among MM patients of different ages. The attrition rates from 1st LOT through 5th LOT among MM patients ≥65 years old were generally higher than MM patients <65 years old, which may be explained by the different baseline conditions of these two groups of MM patients and elderly MM patients are usually frail and presented with more comorbidities ( Lee et al, 2021 ; Tang et al, 2022 ). The median treatment duration was approximately six to 8 months across all LOTs, similar to other real-world study ( Fonseca et al, 2020 ).…”

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review

“…Elderly MM patients often have many comorbidities and generally cannot tolerate intensive chemotherapy or ASCT, resulting in a poorer prognosis than younger patients. The optimal treatment regimen for TIE-NDMM is currently unclear (22)(23)(24). The treatment choice must balance efficacy and toxicity to achieve the best possible effectiveness with the least toxic regimen as far as possible.…”

Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma

“…It is reported that the population and activation of Bregs are increased at the very beginning stage of MM [ 131 ] and during the transition from MGUS to MM [ 132 ]. It also has been observed that the proportion of Bregs in MM patients is closely correlated with treatment efficacy and prognosis [ 133 , 134 ].…”