The R2-ISS in a Multicenter Cohort of Chinese Patients With Newly Diagnosed Multiple Myeloma

Yang, Peiyu; Zhou, Fan; Dong, Yujun; Gao, Guangxun; Xue, Hua; Liang, Xinyue; Yu, Shanshan; Xu, Weiling; Ma, Yanping; Qin, Xiaoqi; Li, Mengyao; Dai, Yun; Jin, Fengyan

doi:10.1097/hs9.0000000000000857

Cited by 6 publications

(2 citation statements)

References 15 publications

(43 reference statements)

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“…Nevertheless, MM often ultimately relapses, leading to a refractory disease. In recent years, the second revision of the International Staging System (R2-ISS) has emerged as a useful prognostic tool for both newly diagnosed and untreated patients with MM and those undergoing autologous stem cell transplantation [3][4][5]. However, these prognostic tools are determined by factors such as beta-2 microglobulin (β2MG), albumin (Alb), lactate dehydrogenase (LDH), and the presence of high-risk chromosomal abnormalities (HRCAs) at the time of diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of the “dynamic” second revision of the international staging system (R2- ISS) in patients with multiple myeloma undergoing anti-CD38 antibody, carfilzomib, and dexamethasone therapy

Kikuchi,

Tsukada,

Kunisada

et al. 2024

Preprint

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Recently, the second revision of the International Staging System (R2-ISS) has emerged as a prognostic tool for multiple myeloma (MM) and is known to be useful for prognostication at the time of diagnosis. Treatment outcomes for MM have significantly improved with the introduction of novel agents; however, eventual relapses nevertheless occur frequently, leading to refractory disease. Clonal evolution during relapse often results in high-risk cytogenetic abnormalities (HRCAs). Hence, a patient’s disease risk may change during their treatment course. We retrospectively analyzed whether R2-ISS influenced prognosis at treatment initiation in patients receiving anti-CD38 antibody, carfilzomib, and dexamethasone (Kd) treatments. HRCAs were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at treatment initiation and defined as dynamic R2-ISS. Data from 60 patients who underwent the defined treatments were analyzed. The median observation period was 13.0 months, with a median progression-free survival (PFS) of 20.7 months. Median overall survival (OS) was not reached. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS (P = 0.00011 and 0.023, respectively). The median PFS for patients with dynamic R2-ISS IV was 4.4 months, and the median OS was 14.6 months, indicating extremely poor outcomes. Multivariate analysis considering disease progression at treatment initiation, triple-class refractory status, and dynamic R2-ISS showed that only R2-ISS significantly affected both PFS and OS (P = 0.0041 and 0.019, respectively). Dynamic R2-ISS therefore shows potential as a prognostic tool in patients with MM who are treated via anti-CD38 antibody + Kd therapy.

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Section: Introductionmentioning

confidence: 99%

Prognostic value of the “dynamic” second revision of the international staging system (R2- ISS) in patients with multiple myeloma undergoing anti-CD38 antibody, carfilzomib, and dexamethasone therapy

Kikuchi,

Tsukada,

Kunisada

et al. 2024

Preprint

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show abstract

“…Moreover, evidence suggests that MM subclones with gain/amp(1q) frequently expand during different treatments [ 9 ], implying that a minor clone of gain/amp(1q) may be associated with CIN in MM. Nevertheless, most centers have now established a cutoff value of 20% [ 4 , 8 , 12 , 17 – 19 ] or 30% [ 20 ] for gain/amp(1q), with only a few using slightly smaller cutoff values of 3.5% [ 10 ], 5% [ 21 ] or 5.5% [ 22 ] for gain/amp(1q). These relatively large cutoff values have made it unclear whether a minor clone of gain/amp(1q) should be considered a high-risk CA in MM and whether it is associated with CIN in MM.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence in situ hybridization reveals the evolutionary biology of minor clone of gain/amp(1q) in multiple myeloma

Cui,

Liu,

et al. 2024

Leukemia

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Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a “two-step” process in the clonal size changes of gain/amp(1q) in MM.

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R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study

Chu,

Wang,

Gao

et al. 2024

Ann Hematol

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We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

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The R2-ISS in a Multicenter Cohort of Chinese Patients With Newly Diagnosed Multiple Myeloma

Cited by 6 publications

References 15 publications

Prognostic value of the “dynamic” second revision of the international staging system (R2- ISS) in patients with multiple myeloma undergoing anti-CD38 antibody, carfilzomib, and dexamethasone therapy

Prognostic value of the “dynamic” second revision of the international staging system (R2- ISS) in patients with multiple myeloma undergoing anti-CD38 antibody, carfilzomib, and dexamethasone therapy

Fluorescence in situ hybridization reveals the evolutionary biology of minor clone of gain/amp(1q) in multiple myeloma

R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study

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