The influencing factors of renal response in newly diagnosed multiple myeloma patients with renal impairment / 中华血液学杂志

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.

Prognostic factors in newly diagnosed multiple myeloma patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To explore the prognostic factors in newly diagnosed multiple myeloma (NDMM) patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation (ASCT) . @*Methods@#We retrospectively assayed 35 NDMM patients with 1q21 amplification/gain who received bortezomib-based chemotherapy followed by ASCT and maintenance therapy between January 2008 and August 2015. @*Results@#①The median age of 35 patients were 49(33-63)years old. Ratio of male to female was 22∶13. Monosomy1q21 amplification/gain was only seen in 3(8.6%) patients, the other 32 patients were with additional cytogenetic abnormalities including 13q14 deletion, t(11,14), t(4,14), t(14,16), 17p deletion and complex karyotype aberrations. ②The complete remission (CR) rate was 57.0% (20/35), the very good partial remission(VGPR) rate was 37.1%(13/35) and the partial remission (PR) rate was 5.7%(2/35) after ASCT. At a median follow-up of 24 (8-85) months, 3-year estimated progression free survival (PFS) and overall survival (OS) rate were (66.5±9.7)% and (69.6±9.9)%, respectively. ③As 13 patients with high-risk cytogenetic abnormalities, the median PFS and OS time was 26 and 28 months. The 3-year estimated PFS and OS was (28.0±15.9)% and (36.5±16.4)%, respectively. Another 22 patients without other high-risk cytogenetic abnormalities, the median PFS and OS time was 54 months and not reached. The 3-year estimated PFS and OS was (71.5±12.7)% and (92.3±7.4)% in this group, respectively. The presence of additional other high-risk cytogenetic abnormalities resulted in significantly shortened PFS (χ2=5.404, P=0.020) and OS (χ2=7.596, P=0.006) compared with no high-risk cytogenetic patients. @*Conclusion@#NDMM patients with isolated1q21 amplification/gain were rarely and usually had additional other cytogenetic abnormalities. The outcomes in this group treated with bortezomib-based chemotherapy followed by ASCT and maintenance therapy were satisfied, additional other high-risk cytogenetic abnormalities made PFS and OS further shortened.

Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients / 中华血液学杂志

Objective@#To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients.@*Methods@#A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform.@*Results@#① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle.@*Conclusions@#1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Prognostic factors in newly diagnosed multiple myeloma patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the prognostic factors in newly diagnosed multiple myeloma (NDMM) patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation (ASCT) . Methods: We retrospectively assayed 35 NDMM patients with 1q21 amplification/gain who received bortezomib-based chemotherapy followed by ASCT and maintenance therapy between January 2008 and August 2015. Results: ①The median age of 35 patients were 49(33-63)years old. Ratio of male to female was 22∶13. Monosomy1q21 amplification/gain was only seen in 3(8.6%) patients, the other 32 patients were with additional cytogenetic abnormalities including 13q14 deletion, t(11,14), t(4,14), t(14,16), 17p deletion and complex karyotype aberrations. ②The complete remission (CR) rate was 57.0% (20/35), the very good partial remission(VGPR) rate was 37.1%(13/35) and the partial remission (PR) rate was 5.7%(2/35) after ASCT. At a median follow-up of 24 (8-85) months, 3-year estimated progression free survival (PFS) and overall survival (OS) rate were (66.5±9.7)% and (69.6±9.9)%, respectively. ③As 13 patients with high-risk cytogenetic abnormalities, the median PFS and OS time was 26 and 28 months. The 3-year estimated PFS and OS was (28.0±15.9)% and (36.5±16.4)%, respectively. Another 22 patients without other high-risk cytogenetic abnormalities, the median PFS and OS time was 54 months and not reached. The 3-year estimated PFS and OS was (71.5±12.7)% and (92.3±7.4)% in this group, respectively. The presence of additional other high-risk cytogenetic abnormalities resulted in significantly shortened PFS (χ(2)=5.404, P=0.020) and OS (χ(2)=7.596, P=0.006) compared with no high-risk cytogenetic patients. Conclusion: NDMM patients with isolated1q21 amplification/gain were rarely and usually had additional other cytogenetic abnormalities. The outcomes in this group treated with bortezomib-based chemotherapy followed by ASCT and maintenance therapy were satisfied, additional other high-risk cytogenetic abnormalities made PFS and OS further shortened.

Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients / 中华血液学杂志

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Impact of 1q21 amplification on prognosis and treatment effect of multiple myeloma / 白血病·淋巴瘤

Objective To investigate the value of 1q21 amplification in newly diagnosed myeloma patients.Methods Fifty-two cases of newly diagnosed multiple myeloma from June 2008 to June 2010 were enrolled.Fluorescence in situ hybridization (FISH) was used to detect the 1q21 amplification,and the clinical characteristics and treatment response were analyzed.Results 1q21 amplification was discovered in 30 of 52 patients (57.7 ％),Clinical characteristics such as gender,malignant pleural effusion,extramedullary plasmacytoma,bone destruction,β2 microglobulin,ALB,hemoglobin,blood calcium,plasma cell proportion,clinical stage seemed to have no correlation with 1q21 amplification.The 52 patients all received bortezomibbased regimens.The response rates were not significant difference between patients with and without 1q21 amplification,the OS was also not significant difference [26 months (6-30 months) vs 30 months (12-85 months),P =0.409],but the patients with presence of 1q21 gain resulted in significantly shorter PFS [8 months (1-30 months) vs 20 months (3--48 months),P=0.019].Multivariate analysis showed 1q21 with more than two additional genetic abnormalities was an independent prognostic predictor (P =0.031).Conclusion 1q21 amplification is one of the adverse prognostic predictors,the response rate is not significant difference between patients with and without 1q21 amplification in bortezomib-based group,but the 1q21 amplification could result in significantly shortened PFS.