Bortezomib-Containing Regimens (BCR) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1846-1846
Author(s):  
Victor H Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Nizar J Bahlis
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Center ◽  
Fisher Exact Test ◽  
Free Survival ◽  
The Impact

Abstract Introduction In patients not eligible for transplant due to age and/or co-morbidities, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor proven to be efficacious in myeloma, have been reported. Based on these findings, we aimed to evaluate the impact of different bortezomib combinations for the treatment of non transplant-eligible MM. Methods All- consecutive patients treated with bortezomib-containing regimens (BCR) at Tom Baker Cancer Center (TBCC) from 01/2006 to June/2015 were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 113 consecutive patients with MM received BCR. Thirty-three patients were treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD), 41 with bortezomib, melphalan and prednisone (VMP) and 39 with bortezomib and dexamethasone (VD). Clinical characteristics are shown in Table 1. At the time of analysis, 20, 17 and 18 patients in the CyBorD, VMP and VD groups are still alive and 14, 33 and 30 have already progressed, respectively. ORR and VGPR rates were 93.9%/75.7%, 80%/53% and 76%/48% (p=0.001) for patients treated with CyBorD, VMP and VD, respectively. Median OS was NR for CyBorD, compared to 41months and 37 months for VMP and VD patients (p=0.6). Median PFS was 16.7 months for CyBorD compared to 17.5 months and 11 months for VMP and VD (P=0.6), respectively. The rate of treatment discontinuation and median number of cycles were: 9%, 26% and 12.8% and 6, 7.5 and 4 cycles for CyBorD, VMP and VD patients, respectively. Patients were to receive 6-9 cycles of treatment and the regimen could be continued to a maximum of 2 years at the discretion of the treating hematologist based on tolerability and response. Nine patients (27%) in the CyBorD group and 17 (41.4%) and 4 (10%) in the VMP and VD group received maintenance treatment. Median OS and PFS was longer for the group receiving maintenance (62 months vs 32 months and 23 months vs 10 months, p=0.007). In conclusion, bortezomib containing regimens are efficacious in the treatment of non-transplant eligible MM. Patients receiving maintenance appeared to exhibit longer PFS and OS. Very elderly patients should be subjected to frailty and comorbidity indexes aiming to decrease toxicity and prolong survival. Table 1. Clinical Characteristics Characteristic CyBorD, n=33 VMP, n=41 VD, n=39 Age (median) 58 58 58 GenderMaleFemale 20 (60.6%)13 (39.4%) 22 (53.6%)19 (46.4%) 26 (66.6%)13 (33.4%) Hb (g/L) 107 110 103 Calcium (µmol/L) 2.4 2.35 2.31 Creatinine (µmol/L) 115.5 103 108 B2microglobulin (µmol/L) 4.1 3.42 5.9 Albumin (g/L) 31 31 30 Stage IStage IIStage III 6 (12.1%)14 (42.4%)13 (45.5%) 9 (21.9%)19 (46.3%)13 (31.8%) 4 (10.2%)16 (41%)18 (48.8%) LDH (IU/L) 185 179 174 BMPC (%) 31 30 33.5 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 2247000 19148000 21107010 Light chain:KappaLambdaBiclonal 16170 29120 24150 High riskStandard risk 5 (15%) 28 6 (14.6%)35 8 (20%)31 Ab: BMPC: Bone marrow plasma cells. Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

High-Risk Cytogenetics Multiple Myeloma: Impact of Consolidation and Maintenance

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2271-2271 ◽  
Author(s):  
Victor Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Jason Tay ◽  
Fariborz Rashid-Kolvear ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Clinical Outcomes ◽  
Research Funding ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Free Survival ◽  
The Impact

Abstract Introduction MM is a very heterogeneous disease for which several new treatments have become available over the past decade. With the advent of novel agents, the outcomes of this disease have improved dramatically. Unfortunately, High-risk myeloma (HRM) defined by the presence of del(17p), t(4;14), t(14;16), del13q by conventional karyotype and hypodiploidy, continues to exhibit poorer outcomes. Based on the above mentioned, we aimed to assess the clinical outcomes of patients with HRM treated at our center. Methods All consecutive HRM patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to March/2016 were evaluated. HRM was defined by FISH and conventional karyotype when available. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. All statistical analyses were performed by using the SPSS 22.0 software. Results 73 consecutive patients with HRM underwent single auto-SCT at our Institution over the defined period. Clinical characteristics are shown in Table 1. Eighty-seven percent of patient received bortezomib-containing regimens as induction regimens. Day-100 response post-ASCT is seen in Table 1. Consolidation was given to 41.7% and maintenance to 79% of cases. At the time of analysis, 43 patients are still alive and 40 have already progressed. Median OS and PFS were 50.8 and 21.9 months, respectively for the whole group. Median OS was 50.4 months for the group receiving consolidation compared to 39 months for those without (p=0.1). In addition, median PFS was longer in the group treated with consolidation (NR, Estimate 25 months vs 13.5 months, p=0.02, Fig1a). Furthermore, OS and PFS were longer in the group receiving some form of maintenance compared to those without (56.3 and 22.5months vs 19.9 and 9 months, p=0.04 and 0.01, respectively) (Fig 1b and c). In conclusion, HRM is an aggressive form of myeloma where the OS and PFS are shorter than the standard risk MM. Consolidation and maintenance strategies seemed to increase both OS and PFS in our current report, but clinical outcomes are still poor. Novel strategies such as immune modulation,check-point inhibition, among others are needed to maximize the impact of the consolidation and maintenance phases in this group of patients. Progression-Free Survival and consolidation Progression-Free Survival and consolidation Figure 1 Overall survival and maintenance Figure 1. Overall survival and maintenance Figure 2 Progression-Free survival and maintenance Figure 2. Progression-Free survival and maintenance Disclosures Jimenez-Zepeda: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Amgen: Consultancy, Honoraria; BMS: Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

scholarly journals Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Bortezomib, Thalidomide and Dexamethasone (VTD) As Induction Therapy for the Treatment of Transplant Eligible Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4505-4505 ◽  
Author(s):  
Victor Jimenez-Zepeda ◽  
Nizar J. Bahlis ◽  
Peter Duggan ◽  
Rafael Alonso ◽  
Juan José Lahuerta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Regimen ◽  
Research Funding ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Similar Response ◽  
Free Survival

Abstract Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. A recent study led by the IFM group showed that the triplet combination of bortezomib, thalidomide and dexamethasone is superior as an induction regimen compared to CyBorD for patients undergoing ASCT. Based on the above-mentioned, we aimed to compare the effect of CyBorD and VTD for the treatment of transplant eligible MM patients in 2 different centers from Canada and Spain. Patients and Methods: The primary objective was to assess ORR and ³VGPR rates after induction and at day-100 post-ASCT, as well as MRD assessed by flow cytometry. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: 101 patients have received CyBorD and 23 have received VTD. Clinical characteristics are shown in Table 1. At the time of analysis, 90 and 19 patients in the CyBorD and VTD are alive of which 25 and 9, respectively, have progressed. ORR and VGPR rates after a median of 4 cycles of induction were 94% and 56.4% for patients treated with CyBorD, and 91% and 78.2% for VTD, respectively (p=0.3 and 0.05). At day-100 post-ASCT, a ³VGPR rate of 84% and 94% was observed for the CyBorD and VTD groups, respectively (p=0.2). MRD negativity and CR rates were higher in the group receiving VTD (36.8% vs 27%, and 61% vs 38%, p=0.3 and 0.01). Furthermore, median OS and PFS did not differ among both groups (p=0.8 and 0.9, respectively) (Fig1a and Fig1b). In Conclusion: CyBorD and VTD appeared to be effective treatment options for transplant-eligible myeloma patients with similar response rates. Our study is in agreement with that reported by the IFM group, showing a higher rate of³VGPR after induction and day-100 post-ASCT in the VTD group. MRD negativity and CR rate appears also higher in the VTD group suggesting a higher degree of response by using animmunomodulatory drug and a proteasome inhibitor together. Overall Survival according to treatment regimen Overall Survival according to treatment regimen Figure 1 Progression-Free survival according to treatment regimen Figure 1. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Bahlis:Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; BMS: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria.

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1845-1845 ◽  
Author(s):  
Victor H Jimenez-Zepeda ◽  
Christopher P. Venner ◽  
Andrew Belch ◽  
Irwindeep Sandhu ◽  
Tatiana Nikitina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Regimen ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
P Value ◽  
Similar Response ◽  
Free Survival

Abstract Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods: The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: Ninety-one patients have received CyBorD and 56 have received LD. Clinical characteristics are shown in Table 1. At the time of analysis, 64 and 32 patients in the CyBorD and LD are alive of which 10 and 11, respectively, have progressed, ORR and VGPR rates were 85.7% and 56% for patients treated with CyBorD, and 83.9% and 64% for LD respectively (p=0.3). Estimated median OS was 40 months for CyBorD compared to 66 months for LD (p=0.156). In addition, median PFS was longer for LD patients compared to CyBorD (26 months vs 16.4 months, p=0.018). The rate of treatment discontinuation was similar between both groups (8.7% vs 10%, p=0.3). In Conclusion: CyBorD and LD appeared to be effective treatment options for NTE myeloma patients with similar response rates. Recognizing the limitations of a retrospective series, it is interesting to note a longer PFS and a trend towards better PFS in the LD group, however, longer follow-up and prospective validation is still required. Table 1. Clinical Characteristics Characteristic CyBorD, n=91 LD, n=56 P value Age (median) 73.9 73.6 0.2 GenderMaleFemale 57 (62.6%)34 (37.4%) 34 (60.7%)22 (39.3%) 0.8 B2microglobulin (µmol/L) 4.9 4.89 0.4 Albumin (g/L) 35 36 0.7 Stage IStage IIStage III 17.7%35.4%46.9% 23.5%37.2%39.3% 0.6 BMPC (%) 32 37.5 0.6 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 501018113 26179010 0.068 Response rateORRCR/nCRVGPRPR 85.7%23%31.8%30.7 83.9%28%37.5%17.8% 0.3 Ab: BMPC: Bone marrow plasma cell Figure 1. Overall Survival according to treatment regimen Figure 1. Overall Survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Venner:J&J: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria. Sandhu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan:Celgene: Honoraria; Jansen: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Bortezomib and High Dose Melphalan (Bor-HDM) Compared to HDM Conditioning for the Treatment of Transplant Eligible Multiple Myeloma: Report from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3189-3189
Author(s):  
Victor H Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Marcia Culham ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Melphalan ◽  
The Impact

Abstract Introduction Preclinical and clinical data suggest that bortezomib in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the quality of response for MM patients undergoing auto-SCT. In the present study, we aimed to assess the impact of Bor-HDM conditioning on ORR, and MRD negativity for MM patients undergoing single auto-SCT at our Institution. Methods All consecutive patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to 06/2015 using Bor-HDM or HDM as conditioning regimen were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. MRD negativity was assessed by multiparameter flow cytometry. All patients received induction chemotherapy before undergoing auto-SCT. Bortezomib was administered intravenously at 1-1.3 mg/m2 on days −5, −2, 1, and 4, while melphalan was given at 200 mg/m2 on day −1. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results Two-hundred and fifty-eight consecutive patients receiving Bor-HDM or HDM alone were evaluated. A total of 85 patients received Bor-HDM conditioning and 173 received HDM. Clinical characteristics and chemotherapy induction regimens are listed in Table 1. At day-100 post auto-SCT a ³VGPR was seen in 83.3% in the Bor-HDM group compared to 67.6% for HDM patients. The CR/nCR rate was higher in the Bor-HDM group (47.6% vs 23.6%) as well as MRD negativity assessed by flow cytometry (30.9% vs 9.7%, p=0.0001). Median OS in the Bor-HDM group was NR compared to 95 months for HDM alone (p=0.572), while median PFS was 39.3 months for Bor-HDM compared to 27 months for HDM (p=0.1). Median OS was shorter in the HR cytogenetic group regardless of the type of conditioning regimen employed (39 months vs NR for SR cytogenetics). In addition, patients who achieved MRD negativity, exhibited a longer OS (NR vs 78 months, p=0.007). Transplant-related mortality (TRM) was similar between both groups (p0.5). In conclusion, Bor-HDM is a safe and efficacious conditioning regimen able to increase the nCR/CR and MRD negativity rates compared to HDM. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed, with special view on the high-risk MM patients where response rates are good but sustainability remains an issue. Table 1. Clinical Characteristics Characteristic Bor/HDM, N=85 HDM alone, N=173 Age (median) 58 59 GenderMaleFemale 51 (60%)34 (40%) 113 (65.3%)60 (34.7%) Hb (g/L) 112 117 Calcium (µmol/L) 2.25 2.29 Creatinine (µmol/L) 85 80 B2microglobulin (µmol/L) 3.3 2.79 Albumin (g/L) 31 35 Stage IStage IIStage III 154723 617333 M-spike (g/L) 34 30 LDH (IU/L) 194 180 BMPC (%) 40 33 Heavy chain:IgGIgAIgDFLC onlyBiclonalIgM 491811511 1142403210 Light chain:KappaLambdaBiclonal 50351 124471 High riskStandard risk 2263 36135 InductionCyBorDVDDexamethasoneRVD 4524016 16544315 Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Disclosures Jimenez-Zepeda: Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding.

Bortezomib-High Dose Melphalan Conditioning for the Treatment of MM Patients Undergoing ASCT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2273-2273
Author(s):  
Victor Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Jason Tay ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Proteasome Inhibitor ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Melphalan

Abstract Introduction Recent data suggests that bortezomib, a proteasome inhibitor, in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the level of response for MM patients undergoing auto-SCT. In the present study, patients receiving induction followed by ASCT with Bor-HDM and HDM alone were evaluated. Methods All consecutive patients undergoing ASCT from 01/2004 to 03/2016 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Most of patients received Bortezomib conditioning at 1.3 mg/m2. As per physician discretion, the dose of 1 mg/m2 was also employed in 30% of cases. Definitions of response and progression were used according to the EBMT modified criteria. MRD negativity was assessed by flow cytometry at day-100 post-ASCT. Results Clinical characteristics are shown in Table 1. Among 301 cases, 129 were treated with Bor-HDM while 172 patients went onto receive HDM alone as part of the conditioning regimen. Induction regimens are shown in Table 1. At the time of analysis, 83% and 58% of patients in the Bor-HDM and HDM group are still alive and 34% and 69.1% of patients have already progressed, respectively. At day-100 post ASCT, ORR of 97%, with CR/VGPR rate of 84.2% was seen in the Bor-HDM group compared to 94.2% and 68.6% in the HDM group (p=0.001). MRD negativity was higher in the Bor-HDM group (33.3%) compared to HDM (12.2%) (p=0.001). Median OS was similar for Bor-HDM and HDM (p=0.864) (Fig 1a). In addition, median PFS did not differ among patients receiving HDM or Bor-HDM (37.7months vs 29.3 months, p=0.2) (Fig1b) In conclusion,Bor-HDMis a conditioning regimen able to provide higher rates ofnCR/CR, as well as MRD negativity compared to HDM alone. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed. Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1 Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1. Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Disclosures Jimenez-Zepeda: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Onyx: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; BMS: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Rank Test ◽  
Genetic Constitution ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
The Impact

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.

scholarly journals Multiple Myeloma Patients with Lenalidomide-Associated Skin Rash Have a Favorable Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4532-4532 ◽  
Author(s):  
Ayumi Kojima ◽  
Yuka Tanaka ◽  
Yuta Kimura ◽  
Daisuke Tsuchimoto ◽  
Rina Etani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Skin Rash ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
The Relationship

Abstract Background: Lenalidomide, one of the immunomodulatory drugs, is an important component of treatment for multiple myeloma. Lenalidomide inhibits the proliferation of tumor cells via antiangiogenesis, induces apoptosis and acts directly on the immune system and tumor microenvironment. Immunomodulatory effects of lenalidomide notably stimulate the production of cytokines and activation of T-cells and natural killer cells. Skin rash is a frequent adverse event of lenalidomide. Some studies have shown a correlation between the efficacy of anti-cancer agents such as tyrosine kinase inhibitors and the development of skin rash. However, the relationship between the development of lenalidomide-associated skin rash and its efficacy is unclear. We conducted a retrospective survey to clarify whether development of skin rash correlates with the efficacy of lenalidomide. Materials and Methods: All patients with multiple myeloma who received lenalidomide at 9 hospitals in Japan from July 2009 to December 2015 were serially registered. The chart review was performed for all identified patients to obtain the following information; age, sex, performance status at the initiation of lenalidomide, International Staging System (ISS) classification, prior chemotherapy regimen, tumor response, development of skin rash and clinical outcomes. A log-rank test was used to assess the relationship between the presence of skin rash and survival. A two-sided p < 0.05 was considered statistically significant. This study received approval from the appropriate ethics committees. Results: We identified 215 patients (92 women and 123 men), with a median age was 69 years (range, 39-86 years). Types of myeloma were as follows: 139 patients of IgG, 43 of IgA, and 29 of Bence-Jones protein. ISS was available for 204 patients, and of these, 63, 73, and 68 patients were classified as ISS stage I, II, and III, respectively. The median number of prior therapies was 2 (range, 0-6); 161 (74.9%) and 46 patients (21.4%) had previously received bortezomib and thalidomide, respectively. Fifty patients (23.3%) had undergone previous autologous stem cell transplantation. Sixty-five patients (30.2%) developed a skin rash after lenalidomide initiation, and the median time to onset of skin rash was 12 days. The patients with and without skin rash were similar with respect to age, type of myeloma, and ISS. The median follow-up of survivors was 28.9 months (range, 1.7-80.3 months). The progression-free survival and overall survival were better in patients who had skin rash than in those who did not (p = 0.009 and p = 0.033, respectively) (Figures A and B). Conclusions: In this study, the progression-free survival and overall survival among patients with skin rash during lenalidomide therapy was significantly superior to the patients without skin rash. Lenalidomide-associeated skin rash in patients with multiple myeloma may be a predictive factor of their clinical outcome. Figure Figure. Disclosures Nagai: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Mundipharma KK: Research Funding.

Delays from neoadjuvant chemotherapy to interval debulking surgery and survival in ovarian cancer

2020 ◽  
Vol 30 (10) ◽  
pp. 1554-1561
Author(s):  
Ying L Liu ◽  
Qin C Zhou ◽  
Alexia Iasonos ◽  
Olga T Filippova ◽  
Dennis S Chi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Debulking Surgery ◽  
Free Survival ◽  
Interval Debulking Surgery ◽  
The Impact

IntroductionDelays from primary surgery to chemotherapy are associated with worse survival in ovarian cancer, however the impact of delays from neoadjuvant chemotherapy to interval debulking surgery is unknown. We sought to evaluate the association of delays from neoadjuvant chemotherapy to interval debulking with survival.MethodsPatients with a diagnosis of stage III/IV ovarian cancer receiving neoadjuvant chemotherapy from July 2015 to December 2017 were included in our analysis. Delays from neoadjuvant chemotherapy to interval debulking were defined as time from last preoperative carboplatin to interval debulking >6 weeks. Fisher’s exact/Wilcoxon rank sum tests were used to compare clinical characteristics. The Kaplan–Meier method, log-rank test, and multivariate Cox Proportional-Hazards models were used to estimate progression-free and overall survival and examine differences by delay groups, adjusting for covariates.ResultsOf the 224 women, 159 (71%) underwent interval debulking and 34 (21%) of these experienced delays from neoadjuvant chemotherapy to interval debulking. These women were older (median 68 vs 65 years, P=0.05) and received more preoperative chemotherapy cycles (median 6 vs 4, P=0.003). Delays from neoadjuvant chemotherapy to interval debulking were associated with worse overall survival (HR 2.4 95% CI 1.2 to 4.8, P=0.01), however survival was not significantly shortened after adjusting for age, stage, and complete gross resection, HR 1.66 95% CI 0.8 to 3.4, P=0.17. Delays from neoadjuvant chemotherapy to interval debulking were not associated with worse progression-free survival (HR 1.55 95% CI 0.97 to 2.5, P=0.062). Increase in number of preoperative cycles (P=0.005) and lack of complete gross resection (P<0.001) were the only variables predictive of worse progression-free survival.DiscussionDelays from neoadjuvant chemotherapy to interval debulking were not associated with worse overall survival after adjustment for age, stage, and complete gross resection.

scholarly journals Transarterial Chemoembolization of Hepatocellular Carcinoma with Oncozene Microspheres: An Initial, Short-Term Clinical Experience—A Retrospective, Matched, Comparison Study

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 600
Author(s):  
Matthew L. Hung ◽  
Jerry Jiang ◽  
Harry Trieu ◽  
Frank Hao ◽  
Navid Eghbalieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Embolic Agent ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Short Term ◽  
Free Survival

Background: The purpose of this study is to describe a single institution’s experience using Oncozene (OZ) microspheres for transarterial chemoembolization (OZ-TACE) of hepatocellular carcinoma (HCC), and to compare tolerability, safety, short-term radiographic tumor response, progression-free survival (PFS), and overall survival (OS) of these procedures to TACE (LC-TACE) performed with LC beads (LC). Methods: A retrospective, matched cohort study of patients undergoing DEB-TACE (drug-eluting bead transarterial chemoembolization) with OZ or LC was performed. The cohort comprised 23 patients undergoing 29 TACE with 75 or 100 μm OZ and 24 patients undergoing 29 TACE with 100–300 μm LC. Outcome measures were changes in liver function tests, complications, treatment tolerability, short-term radiographic tumor response according to modified RECIST criteria for HCC, PFS, and 1-year OS. The Mann–Whitney U test, Fisher exact test, and log rank test were used to compare the groups. Results: The BCLC or Child–Pugh scores were similar between the OZ and LC group. However, the two groups differed with respect to the etiology of background cirrhosis (p = 0.02). All other initial demographic and tumor characteristics were similar between the two groups. OZ-TACE used less doxorubicin per treatment compared to LC-TACE (median 50 vs. 75 mg; p = 0.0005). Rates of pain, nausea, and postembolization syndrome were similar, irrespective of the embolic agent used. OZ-TACE resulted in an overall complication rate comparable to LC-TACE (20.7% vs. 10.3%; p = 0.47). LC-TACE resulted in a higher percent increase in total bilirubin on post-procedure day 1 (median 18.8 vs. 0%; p = 0.05), but this difference resolved at 1 month. Both OZ-TACE and LC-TACE resulted in similar complete (31% vs. 24%) and objective (66% vs. 79%) target lesion response rates on 1-month post-TACE imaging. Both OZ-TACE and LC-TACE had similar median progression-free survival (283 vs. 209 days; p = 0.14) and 1-year overall survival rates (85% vs. 76%; p = 0.30). Conclusion: With a significantly reduced dose of doxorubicin, TACE performed with Oncozene microspheres in a heterogeneous patient population is well-tolerated, safe, and produces a similar radiological response and survival rate when compared to LC Bead TACE.

scholarly journals Improved Survival of Patients with Myelofibrosis in the Last Decade

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 50-51
Author(s):  
Lucia Masarova ◽  
Prithviraj Bose ◽  
Naveen Pemmaraju ◽  
Lingsha Zhou ◽  
Sherry A. Pierce ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Myeloproliferative Neoplasm ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Grant Support ◽  
Before And After

Introduction: The myeloproliferative neoplasm myelofibrosis (MF) is associated with reduced overall survival (OS) compared to the general population. In 2011, the JAK1/2 inhibitor ruxolitinib, was approved in the USA for the treatment of intermediate and high-risk MF. Long-term follow-up of patients in pivotal phase 3 studies showed survival benefit of ruxolitinib therapy. Objective: We sought to evaluate the outcome of patients with MF diagnosed before and after the year of 2010 to assess whether OS changed in the past decade in the era of ruxolitinib. Methods: We retrospectively reviewed the charts of 1346 patients with MF who presented to our institution in the last 25 years and compared clinical parameters and outcomes between those presented before and after the year of 2010 (before / after y. 2010). Newly diagnosed MF patients and patients within 12 months from diagnosis who were previously only treated with supportive therapy (danazol, growth-factors, steroids) were included. Cytogenetics (≥10 metaphases) was classified according to Gangat, JCO, 2011. Molecular analysis (≥ 28 genes) was performed only after y. 2010 by using next generation sequencing platform. Fisher exact test and χ2 were used for analysis of categorical variables. Overall survival (OS) was estimated using the Kaplan-Meier method and comparison was done by the log-rank test. Results: Among the 1346 patients, 806 (60%) patients were seen after y. 2010. Median age of all patients was 65 years (range, 20-94), 62% were males. Patient characteristics with comparison between groups are shown in Table 1. Patients after y. 2010 were older, with lower WBC and lower lactate dehydrogenase, but had more symptoms. The distribution of IPSS scores between groups were comparable at around 10% for low, 36% for intermediate-1, 20-25% for intermediate-2 and ~30% for high risk. Eighty-five and 80% of patients before and after y. 2010, respectively, received therapy for MF at our institution. Overall, 78 patients (37 after y. 2010) underwent stem cell transplantation. Among treated patients at our institution, 25% (n 117) and 37% (n 241) before and after y. 2010 received ruxolitinib during their follow-up. Ruxolitinib therapy was initiated with a median time of 2 months (range, 0.2-156) from presentation to our institution, longer in those before y. 2010 (11 vs 1 months in patients after y. 2010, respectively, p = 0.001) After a median follow-up of 30.4 months (range, 0.9-266); 659 (49%) of patients died. More deaths were noticed in those before y. 2010 (74% vs 32 %, respectively, p &lt; 0.001); but these patients had also longer follow-up (37.5 months vs 25 months, p &lt; 0.001). Eighty-five patients (10%) developed acute leukemia: 2 cases per 100 person-years per observation for both groups. Patients after y. 2010 had superior OS to those before y. 2010 with HR 0.7 (95% CI: 0.59-0.82), p &lt; 0.001, Figure 1. Superior OS was observed in all patients after y. 2010 (vs before y. 2010) when stratified by IPSS score (higher equals for combination of int -2 and high, Figure 2), or age (cutoff of 65 years, Figure 3). Patients exposed to ruxolitinib had superior OS regardless of being diagnosed before or after y. 2010, with respective medians of 98 (95% CI: 78-118) and 91 (95% CI: 73-109) months (details to be presented at the conference). Conclusion: Our results demonstrate that survival of patients with MF has improved in the last decade. Survival has improved in younger and older patients as well as in those with more advanced disease (per IPSS risks). Many factors may have contributed to the observed improvement in outcome of MF patients, including new therapies, e.g. ruxolitinib, as well as improved supportive management and disease awareness. Disclosures Bose: Blueprint Medicines Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; NS Pharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Honoraria, Research Funding; Promedior, Inc.: Research Funding. Pemmaraju:Daiichi Sankyo: Research Funding; DAVA Oncology: Honoraria; Blueprint Medicines: Honoraria; Roche Diagnostics: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Honoraria; Incyte Corporation: Honoraria; MustangBio: Honoraria; Plexxikon: Research Funding; Samus Therapeutics: Research Funding; SagerStrong Foundation: Other: Grant Support; Novartis: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; LFB Biotechnologies: Honoraria; Stemline Therapeutics: Honoraria, Research Funding; Cellectis: Research Funding. Kantarjian:Novartis: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; Astex: Research Funding; Takeda: Honoraria; Agios: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding. Verstovsek:CTI Biopharma Corp: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; ItalPharma: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; AstraZeneca: Research Funding.

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