Combination therapy based on bortezomib for 102 patients with newly-diagnosed multiple myeloma: a Chinese experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5116-5116
Author(s):  
Jingsong He ◽  
Li Yang ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
Xiaojian Meng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Neuropathy ◽  
Combination Therapy ◽  
Adverse Events ◽  
Chinese Population ◽  
Median Overall Survival ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Significant Difference

Abstract Abstract 5116 Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Metohds: Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.

Combination Therapy Based on Bortezomib for Newly-Diagnosed Multiple Myeloma: a Chinese Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5036-5036
Author(s):  
Li Yang ◽  
Jing-Song He ◽  
WenJun Wu ◽  
Xiujin Ye ◽  
Jimin Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Combination Therapy ◽  
Combination Chemotherapy ◽  
Chinese Population ◽  
Conflicts Of Interest ◽  
Malignant Neoplasm ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Abstract 5036 Multiple myeloma (MM) is a malignant neoplasm of plasma. With conventional chemotherapy, the rates of complete remission (CR) or very good partial remission (VGPR) are still low. Little has been reported on Bortezomib-based therapies specifically in the Chinese pateitns with MM. Here we report our results with combination therapy based on bortezomib in the Chinese population. We investigated the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Methods: Between June 2006 and June 2010, 61 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on Bortezomib. Forty-two patients were male and 19 were female. Median age was 59 years (range 37–86 years). Forty-four patients were stage 3 according to the International Staging System, 6 patients were stage 2 and 11 patients were stage 1. The conbinations included dexamethasone, dexamethasone plus subsequent thalidomide and dexamethasone plus cyclophosphamide. In detail, Bortezomib was at the dose of 1.3 mg per square meter IV on days 1, 4, 8, 11 and dexamethasone at 20 mg per square meter IV daily on the day of bortezomib and the day after, with or without daily oral thalidomide that was escalated from 100 mg to 200 mg (BD group or BDT group) or plus cyclophosphamide at 0.2 per square meter IV on days 1 to days 4 (BDC group). Thirty-four patients were in BDT group, 12 in BD group and 15 in BDC group. All patients received a median of three cycles of therapy (range 1–6). The IMWG criteria were used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The proportions of patients with very good partial response (VGPR) or better were 38% (13/34), 25% (3/12) and 60% (9/15) in BDT, BD and BDC group, respectively; 44% (15/34), 33% (4/12) and 33% (5/15) achieved partial response (PR). Therefore the overall response (VGPR plus PR) were 82% (28/34), 58% (7/12) and 93% (14/15). Three patients died with severe infection without disease progression. Grade 3–4 toxicities included fatigue (4/34, 1/12 and 4/15), thrombocytopenia (8/34, 3/12 and 5/15), diarrhea (4/34, 2/12 and 2/15) and infection (7/34,3/12,6/15) in BDT, BD and BDC group, respectively. Grade 1–2 neuropathy were occurred in 20 patients (59%), 6 patients (50%) and 9 patients (60%) and grade 3–4 were occurred in 6 (18%), 1 (8%) and 1 (7%) in BDT, BD and BDC group, respectively. Herpes zoster occurred in 6 patients (18%), 1 patients (8%) and 2 patients (13%) respectively. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on Bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC or BDT regimens may be more superior than BD in Chinese population. There were relative lower rates of grade 3–4 neuropathy and DVT/PE in the Chinese patients with MM receved combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.

Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients.

1991 ◽  
Vol 9 (3) ◽  
pp. 444-448 ◽  
Author(s):  
M Boccadoro ◽  
F Marmont ◽  
M Tribalto ◽  
G Avvisati ◽  
A Andriani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Cell Labeling ◽  
Induction Treatment ◽  
Treatment Groups ◽  
Significant Difference ◽  
Risk Patients ◽  
Beta 2 ◽  
Beta 2 Microglobulin

The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P less than .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v 37.0 months, P less than .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m greater than or equal to 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to MP.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Effect of Amp5q31 and Del12p13 on Survival of Patients with Multiple Myeloma Treated with Novel Agent-Based Regimens: A Single Center Experience on 172 Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1811-1811
Author(s):  
Evangelos Terpos ◽  
Efstathios Kastritis ◽  
Despoina Iakovaki ◽  
Maria Gkotzamanidou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Survival ◽  
Chromosomal Aberrations ◽  
Median Overall Survival ◽  
Chromosomal Abnormalities ◽  
Newly Diagnosed ◽  
Single Center ◽  
Agent Based ◽  
Novel Agent

Abstract Abstract 1811 The presence of chromosomal aberrations is a characteristic feature of multiple myeloma (MM). Recently, Avet-Loiseau et al reported that amp5q31.3 and del12p13.31, detected by high-density, single-nucleotide polymorphism arrays analysis correlate with prognosis in MM patients who were treated upfront with conventional chemotherapy (JCO 2009; 27:4585–90). The aim of our study was to evaluate the effect of these chromosomal abberations on survival of patients with newly diagnosed MM or with relapsed/refractory myeloma who were treated with novel agent-based regimens. We studied 172 MM patients who were treated in a single center in Athens (Greece) during a 4-year period (2007–2011); 76 were newly-diagnosed and were treated upfront with either bortezomib- or IMiD-based regimens and 96 had relapsed or refractory MM and were treated with the combination of lenalidomide and dexamethasone with or without bortezomib (RD vs. VRD) based on the presence of previous peripheral neuropathy (Dimopoulos et al, Leukemia 2010;24:1769–78). A combined methodological approach of G-banding karyotypic analysis and interphase fluorescence in situ hybridization (FISH) was performed in all patients. G-banding analysis was performed according to the European Cytogenetic Guidelines and Quality Assurance (ECA, 2006). The clonality criteria and the karyotypic description followed the recommendations of the International System for Human Cytogenetic Nomenclature (ISCN, 2009). FISH was performed according to the Recommendations for FISH in MM (European Myeloma Network) on uncultured BM, either on cytoplasmic immunoglobulin-enhanced cells (cIg-FISH) or on nuclei from purified CD138+ plasma cells. Commercially available DNA probes (Abott-VYSIS) were used for the detection of del17p, del13q, add1q21, t(4;14) and t(14;16). The probes RP11-96J7 and RP11-578N7 (labeled by Empire Genomics, NY, USA) were used to detect amp5q31 and del12p13. The frequency of the studied chromosomal abnormalities is depicted in the table. There was a strong correlation between the presence of amp5q31 with hyperdiploidy (p=0.012) but amp5q31 did not correlate with the presence of any other of the studied chromosomal aberrations. The presence of del12p13 was correlated with the presence of del13q (p=0.001), t(4;14) (p=0.009) and del17p (p=0.005). Add1q21 also correlated with del13q (p<0.001), t(4;14) (p<0.001) and del17p (p=0.007). In patients with relapsed/refractory MM, who received either RD or VRD, the median overall survival was 19 months. Patients with amp5q31 had a median survival of 18 months (95% CI: 13–23 months) vs. 21 months of the others (95% CI: 8–35 months; p=0.737), while patients with del12p13 had a median survival of 27 months (95% CI: 0–57 months) vs. 19 months of the others (95% CI: 10–27 months; p=0.767). Of the other studied cytogenetic abnormalities, the presence of del17p (11 vs. 26 months; p=0.001), amp1q21 (12 vs. 26 months; p=0.001) and del13q by FISH (11 vs. 26 months; p=0.025), but not of t(4;14) (p=0.521), were associated with inferior overall survival. In patients with newly-diagnosed MM, the median overall survival was 57 months. The median survival of patients with amp5q31 was 46 months vs. 57 months of all others (p=0.315) and for patients with del12p13 has not been reached vs. 57 months of all others (p=0.379). In conclusion, amp5q31 and del12p13 are recurrent chromosomal abnormalities in MM. Amp5q31 is not associated with the presence of other genetic features, except hyperdiploidy. αmp5q31 or 12p13 was not predictive of survival ιn our series. However, further studies are needed in patients with newly diagnosed MM who receive novel agents upfront to validate the prognostic importance of amp5q31 and del12p13.TableCytogenetic abnormalityPatients at diagnosis (n=76)Relpased/refractory patients (n=96)p-valueamp5q3112 (15.7%)20 (20.8%)0.271amp5q31 as sole anomaly5 (6.5%)7 (7.2%)0.674del12p138 (10.5%)16 (16.6%)0.171del13q28 (36.8%)28 (29.1%)0.279del17p13 (17.1%)15 (15.6%)0.765add1q2115 (19.7%)26 (27%)0.303t(14;16)1 (1.3%)1 (1%)0.832t(4;14)4 (5.2%)10 (10.4%)0.221Hyperdiploidy/hypodiploidy10 (13.1%)/6 (7.8%)11 (11.4%)/13 (13.5%)0.301 Disclosures: No relevant conflicts of interest to declare.

Clinical Efficacy of Pegylated Liposomal Doxorubicin, Vincristine and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5212-5212
Author(s):  
Wen Wu ◽  
Xiaodong Gao ◽  
Lan Xu ◽  
Hua Yan ◽  
Zhixiang Shen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Adverse Events ◽  
Median Time ◽  
Liposomal Doxorubicin ◽  
Gastrointestinal Symptoms ◽  
Pegylated Liposomal Doxorubicin ◽  
High Response Rate ◽  
Newly Diagnosed

Abstract Object: To investigate the short-term and long-term efficacy and toxicity of pegylated liposomal doxorubicin, vincristine and dexamethasone (DVD) in patients with newly diagnosed multiple myeloma (MM). Methods: Twenty-five patients (13 males, 12 females, median age 55 years) with newly diagnosed multiple myeloma were treated with pegylated liposomal doxorubicin 40 mg/m2 and vincristine 2 mg intravenously on day 1 plus dexamethasone 40 mg intravenously or orally on days 1–4 (DVD) for median 4.5 (2–8) cycles. Treatment was repeated every 4 weeks. Response was evaluated according to the International Uniform Response Criteria for Multiple Myeloma (2006) before initiation of each course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results: After 4.5 (2–8) courses of the median cycles, clinical response was observed in 20 patients (80%), including complete response in 4 (16%), very good partial response in 3 (12%), partial response in 10 (40%), minimal response in 3 (12%) and stable disease in 2 (8%). The median time to initial response was 1.2 months and the median time to best response was 4 months. After 25 (2–50) months of median follow-up, the median progression-free survival was 20 months, while the median overall survival has not yet been reached. The overall survival rate was 72% (18/25). The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 10, constipation in 9 patients), neutropenia (7 patients), anemia (6 patients) and thrombocytopenia (4 patients). DVD was associated with more hand-foot syndrome (4 patients) and mucitis (2 patients). Conclusions: DVD scheme is an effective therapy with a high response rate and manageable toxicities for patients with newly diagnosed multiple myeloma.

scholarly journals Comparison of bortezomib-cyclophosphamide-dexamethasone versus bortezomib-dexamethasone based regimens in newly diagnosed multiple myeloma patients

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Rafiye Ciftciler ◽  
Hakan Goker ◽  
Yahya Buyukasik ◽  
Nilgun Sayınalp ◽  
Ibrahim C. Haznedaroglu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Mortality Rate ◽  
Care Center ◽  
Tertiary Care ◽  
Progression Free Survival ◽  
Tertiary Care Center ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Significant Difference

The treatment landscape and clinical outcome of multiple myeloma (MM) patients have changed in the last decades, with an improved median survival of 8-10 years. This study aimed to evaluate the bortezomib, cyclophosphamide and dexamethasone (VCD) regimen versus bortezomib and dexamethasone (VD) regimen in patients with newly diagnosed MM. This study has been performed in a retrospective manner. One hundred and three patients with newly diagnosed MM who received chemotherapy at our tertiary care center between the years of 2009 and 2018 were evaluated. A total of 103 patients were included. The 5-year overall survival (OS) for patients who received VD regimen and patients who received VCD regimen were 75% and 83%, respectively. The OS for VD patients was 113.1±12.5 versus 122.2±9.5 months for VCD patients with no statistically significant difference (P=0.47). The 5- year PFS (progression free survival) for patients who received VD regimen and patients who received VCD regimen were 66% and 75%, respectively. The PFS for VCD patients was higher than the PFS for VD patients (67.1±7.4 versus 97.7±13.4 months), but no statistically significant difference was observed (P=0.59). Relapse rate (P=0.002) and mortality rate (P=0.01) were higher in VD group than VCD group and they were statistically significant. The OS and PFS were clinically longer in patients receiving VCD regimen than in patients receiving VD regimen, although not statistically significant. Cyclophosphamide should be given to patients at physician discretion and depending on patient’s frailty function.

scholarly journals High Risk Older AML Patients May be Benefited from the Treatment of Decitabine Combined Wih CAG Regimens

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4953-4953
Author(s):  
Xia Xiao ◽  
Mingfeng Zhao ◽  
Qi Deng ◽  
Qing Li ◽  
Juan Mu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Adverse Events ◽  
Older Patients ◽  
Median Overall Survival ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Ecog Performance Status ◽  
Secondary Aml ◽  
Number Of Patients

Abstract Patients over age 60 maked up more than 50% of newly diagnosed patients with acute myeloid leukemia (AML). Futhermore, with an aging population, more and more older AML patients were diagnosed in China. But the treatment approaches of this disease were variable, with many uncertainties and controversies. Treatment options for older patients with adverse prognostic features, such as poor performance status, unfavorable cytogenetics or an antecedent hematologic disorder were limited, and outcomes were poor. Aggres­sive induction chemotherapy had a high mortality and relatively low efficacy in this population. There were several new therapeutic schemes for older patients with AML. CAG regimens consisting of low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor for the treatment of older patients with AML showed higher rates of CR (42-68%). Decitabine, a DNA-hypomethylating agent induces differentiation and apoptosis of leukemic cells. The current National Comprehensive Cancer Care guidelines suggested decitabine as alterative options for older patients with AML. Previous studies have shown that decitabine demonstrated efficacy in a phase II multicenter study of older patients with AML, with a CR rate of 25%, 30-day mortality of 7%, median overall survival 7.7 months and little extramedullary toxicity. In our study, decitabine(15 mg/m2/d, d1-5) combined with CAG regimens (aclarubicin 20 mg/d, d3-6, Ara-C 10 mg/m2, q12h, d3-9, G-CSF 300ug, qd, d1-9) treated 27 older patients with AML, repeated every 4 weeks. Effectiveness and safety were assessed. 27 older patients with newly diagnosed AML who were in Tianjin First Central Hospital of China from January 2011 to December 2013 were enrolled in our study. They were all treated with decitabine combined with CAG regimens. The characteristics of the 27 patients were described in Table I. The study population included 15 males and 12 females, with a median age of 68 years (range 60-79 years). All patients had Eastern Cooperative Oncology Group (ECOG) performance status of <3. Cytogenetics were classified according to criteria of the Cancer and Leukemia Group B(CALGB), and were adverse in 11 patients (40.7%) and intermediate in 16 patients (59.3%). No patient had favorable cytogenetics. 12 patients (44.4%) had secondary AML or an antecedent MDS or myeloproliferative disorder. Molecular diagnostics with mutations of FLT3-ITD in 6 patients (22.2%), NPM1 in 7 patients (25.9%) patients and JAK-2 in 4 patients (14.8%). Clinical responses, survival and adverse events of all 27 patients were analyzed. The median treatment cycle was 4 cycles. Rate of complete remission, overall response rate and a 30-day mortality rate were 40.1%, 66.7%, 7.4%, respectively. The median overall survival and median recurrence-free survival were 13.0months (95%CI, 7.0-18.0 months ) and 7.0 months (95%CI, 3.0-11.0 months), respectively. Adverse events in the regimens were mainly included myelosuppression, infection, nausea, vomiting and liver dysfunction. The adverse events could be well tolerated after managements. In conclusion, the treatment of decitabine combined with CAG regimens was found to be feasible and useful in high-risk older patients with AML. This regimen was a well-tolerated therapeutic alternative, was effective in producing remissions lasting several months or disease stabilization in high-risk older patients with AML. Table 1. The characteristics of newly diagnosed patients with AML Total number of patients n=27 median age(range) 68 years(60-79 years) Male/female 15/12 (1.25/1) ECOG performance status, n (%) 0 5 (18.5%) 1 10 (37.0%) 2 12 (44.4%) Cytogenetics, n (%) Adverse 11 (40.7%) Intermediate 16 (59.3%) secondary AML, n (%) MDS 6 (22.2%) myeloproliferative 5 (18.5%) Other tumors 1 (3.7%) Molecular mutations, n (%) FLT3-ITD 6 (22.2%) NPM1 7 (25.9%) JAK-2 4 (14.8%) Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Outcomes of Non-Traditional Lenalidomide, Bortezomib, and Dexamethasone Regimens in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Shawn O. Streeter ◽  
Omar Nadeem ◽  
Paul G. Richardson ◽  
Jacob P. Laubach ◽  
Clifton C. Mo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Descriptive Analysis ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Staging System ◽  
Newly Diagnosed ◽  
Cutaneous Toxicity ◽  
Free Survival ◽  
Significant Difference

Introduction Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard first-line regimen for patients with newly diagnosed multiple myeloma and is associated with high response rates and improvement in progression-free survival and overall survival compared to traditional chemotherapy regimens. Traditional (RVD Classic, RVD Lite) and non-traditional (RVD Premium Lite, RVD Ultra Lite) variations of the RVD regimen are utilized at Dana-Farber Cancer Institute (DFCI) and have not been fully evaluated in terms of safety and tolerability. RVD Premium Lite is administered in a 28-day cycle with weekly bortezomib; whereas, RVD Ultra Lite administers three weekly doses of bortezomib instead of four (Table 1). These two regimens have not been fully evaluated in terms of safety, tolerability, and efficacy. Selection is based on provider preference in addition to flexibility of dosing schedule. The regimens also allow for convenience of weekly dosing while keeping dose intensity. This retrospective, descriptive analysis is the first study to explore the safety, tolerability, and efficacy of four different RVD regimens used at DFCI. Methods This single-center, retrospective, descriptive analysis identified 90 newly diagnosed patients with multiple myeloma treated at DFCI main campus for &gt;2 cycles of an RVD-based regimen in the front-line setting. We reviewed patients started on treatment from January 2017 to December 2019. Patients were excluded if treated primarily at an outside institution or satellite campus. Results A total of 90 patients were included between January 2017 to December 2019, and median age was 69.5 years (range 44-87). Most patients had either standard-risk or unknown cytogenetics. Of the 44 patients with available International Staging System (ISS) information, the majority were R-ISS/ISS I or II. The most common M-protein type at diagnosis was IgG (56.7%), followed by light chain restricted disease (25.6%). In terms of traditional and non-traditional RVD regimens, most patients received RVD Classic (33.3%) or RVD Ultra Lite (32.2%), followed by RVD Lite (23.3%) and RVD Premium Lite (11.1%). Patients in RVD Lite and RVD Ultra Lite groups were of older age when compared to the RVD Classic group (P&lt;0.001). Lenalidomide dosing delays and reductions trended higher in the RVD Classic regimen at 14.3%, followed by RVD Ultra Lite at 12.3%. Bortezomib dosing delays and reductions were similar between the RVD Lite and RVD Classic regimens at 11.8% and 11.2%, respectively. Overall, combined lenalidomide and bortezomib dosing delays/reductions trended higher in the RVD Classic (14.3%/11.2%) and RVD Lite (11.0%/11.8%) compared to RVD Ultra Lite (12.3%/9%) and RVD Premium Lite (10.8%/9.6%). The most common toxicities noted with all variations of the RVD regimen were peripheral neuropathy, cutaneous toxicity, infection, diarrhea, and constipation. The highest rates of adverse events among all RVD regimens were infection and peripheral neuropathy. Peripheral neuropathy was slightly higher in the RVD Premium Lite and RVD Classic regimen at 8.43% and 8.70%, respectively, compared to RVD Lite and RVD Ultra Lite at 7.1% and 7.7%, respectively. No significant difference in toxicities were seen when regimens were compared (p=0.1369). Intolerance leading to therapy change trended higher in the RVD Lite group at 23.8%, followed by RVD Classic and RVD Ultra Lite at 16.7% and 10.3%, respectively. Nineteen percent of patients in the RVD Lite group had minimal response or progression leading to therapy change, which was highest among all RVD regimens. Rate of transplant was highest in the RVD Classic group at 36.7%, followed by RVD Premium Lite at 20%. There was no significant difference in intolerance, minimal response or progression, maintenance, continued induction or planned change, transplant, and death between regimens (p=0.089). In terms of progression-free survival, no differences were seen between the groups (p=0.36). Conclusion In conclusion, the current investigation allowed us to assess the safety, tolerability, and efficacy of traditional and non-traditional variations of the RVD regimen in multiple myeloma used at our institution. There are minimal differences between each regimen when toxicities are managed appropriately. Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Mo:Celgene/BMS: Membership on an entity's Board of Directors or advisory committees.

Sign in / Sign up

Export Citation Format

Share Document