OAB-001: Overall survival and progression-free survival by treatment duration with Daratumumab + Lenalidomide/Dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study

2021 ◽  
Vol 21 ◽  
pp. S1
Author(s):  
Philippe Moreau ◽  
Thierry Facon ◽  
Shaji Kumar ◽  
Torben Plesner ◽  
Robert Z. Orlowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Duration ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Free Survival

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.

Prognostic Value of Syndecan-1 in Multiple Myeloma and its Relationship with Other Prognostic Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2402-2402 ◽  
Author(s):  
Shaji Kumar ◽  
Emily Blood ◽  
Martin M. Oken ◽  
Philip R. Greipp
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Type I ◽  
Newly Diagnosed ◽  
Clinical Markers ◽  
Free Survival

Abstract Background: Syndecan-1 (CD138) is a heparan sulfate bearing proteoglycan found on various epithelial cells as well as on B lineage cells depending on its stage of development. Syndecan-1 (CD138) is abundantly expressed by plasma cells, especially myeloma cells. The extra cellular domain along with the heparan sulfate side chains can be cleaved off the cell surface and can be detected in the serum as soluble syndecan. Syndecan possibly plays a multifunctional role in the biology of myeloma. It has been shown to be an independent prognostic factor in patients with multiple myeloma. It has also been shown to promote myeloma cell growth through different mechanisms. Its expression has also been suggested to correlate with bone disease in MM. Methods: In this study we studied serum levels of soluble syndecan in newly diagnosed MM patients enrolled in the Eastern Cooperative Oncology Group (ECOG) E9486 and its associated correlative laboratory clinical trial E9487. We evaluated the prognostic value of syndecan in MM and its relationship to other known prognostic factors for this disease. In addition, syndecan levels were correlated with clinical and laboratory markers of bone disease. Results: A total of 501 patients were studied and the median serum syndecan-1 was 158 ng/mL. Syndecan levels correlated positively with other prognostic factors and markers of tumor burden such as β2-microglobulin (correlation coefficient 0.3; P <0.00001), labeling index (0.25; <0.0001), creatinine (0.23; <0.0001), soluble IL6 receptor (0.3; <0.0001), BM plasma cell percentage (0.16; <0.0006), and disease stage (P=0.0007). Significant differences in the overall and progression free survival was found between two groups of patient separated using the median value as cut-off. The High syndecan group had a median overall survival of 36.3 months compared to 49.3 months for the low syndecan group (P < 0.0001). Similarly, the high syndecan group had progression free survival of 25.4 months compared to 33.5 months for the low syndecan group (P < 0.0001). In a proportional hazards model including syndecan-1 as well as labeling index, β2M, Platelet count, IL-6R, syndecan-1 retained its prognostic value for overall survival (HR 1.3, P = 0.021). Syndecan levels were correlated with various bone markers including C-terminal telopeptide of type I collagen (ICTP), osteocalcin (OC), C-terminal type I procollagen (PICP), bone-specific alkaline phosphatase (BAP), and tartrate resistant alkaline phosphatase (TRAP) and were found to correlate only with ICTP (0.25, P < 0.0001). No correlation was found between clinical markers of bone disease including presence of lytic lesions, osteoporosis and pathologic fractures on X-rays or bone pain. Conclusion: In this large study, we once again confirm the prognostic value of serum syndecan-1 levels in large group of patients with newly diagnosed myeloma. Syndecan-1 level correlates with other disease markers. Syndecan levels also correlated with ICTP, a marker of bone turnover, though no strong correlation was found between syndecan levels and clinical markers of myeloma bone disease. The biological basis of these finding needs further evaluation.

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 Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall survival and progression free survival in the Danish population

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0188988 ◽  
Author(s):  
Rasmus Sørrig ◽  
Tobias W. Klausen ◽  
Morten Salomo ◽  
Annette J. Vangsted ◽  
Ulf Christian Frølund ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Danish Population ◽  
Free Survival

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.

A Randomized Clinical Trial of Lenalidomide and Dexamethasone with and without Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Interim Study Results,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4142-4142 ◽  
Author(s):  
Lijun Dai ◽  
Amy O'Sullivan ◽  
Ryan Kennedy ◽  
Mohammad Abbas ◽  
Yongli Shuai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Low Dose ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 4142 Introduction: High dose chemotherapy combined with autologous stem cell transplantation (ASCT) as opposed to conventional chemotherapy improved progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) and is currently the standard of care for newly diagnosed MM patients less than 65 years old. Over the last decade, novel agents such as lenalidomide or bortezomib have dramatically improved MM outcomes with similar response rates as ASCT and the role of upfront ASCT has become more controversial. Therefore the goal of this randomized clinical trial is to determine the role of upfront ASCT in newly diagnosed myeloma patients receiving novel agent lenalidomide and low-dose dexamethasone induction. Methods: Patients aged ≥18 years with newly confirmed, measurable MM in stage 2 and 3 (Salmon Durie) and meeting CRAB criteria were enrolled. Patients were randomized to transplant (Arm A) or to non-transplant (Arm B). Patients in Arm A received 4 cycles of lenalidomide (25mg days 1 – 21) plus low-dose dexamethasone (40mg days 1,8,15,22) followed by ASCT conditioned with 200 mg/m2 melphalan (LD+ASCT); Arm B patients received 8 cycles of lenalidomide plus low-dose dexamethasone (LD alone). Both arms received stem cell collection after 4 cycles of therapy if patients achieved at least a partial remission (PR). Patients with stable disease (SD) or progressive disease (PD) went off study. The primary objective was to compare best response. The secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS) and evaluation of secondary malignancies in both arms. Results: From February 2008 to May 2011, 44 patients with newly diagnosed MM were randomized. The patient characteristics were as follow: median age of the patients was 61.7 years (range 48∼75), 45.5% female and 55.5% male patients, ISS stage I 31%, II 51% and III 18%. 40 patients were eligible for evaluation and 20 patients were randomized to Arm A or Arm B, respectively. The data were analyzed according to latest IMWG response criteria (Blood. 2011 May 5;117(18):4691–5). In an intention to treat analysis, patients in Arm A (LD + ASCT), achieved a 100% Overall Response Rate (ORR) with 40% PR (n=8) and 60% Very Good Partial Response (VGPR) (n=12). In Arm B (LD only) the ORR was 75% (n=15), including 15% CR (n=3), 35% VGPR (n=7), 25% PR (n=5), 20% SD (n=4) and 5% PD (n=1). The ORR was significantly superior in the LD+ASCT group compared to LD alone (p=0.047). After a median follow-up of 25.3 months, 17 patients have PD (8 in LD+ASCT and 9 in LD alone), 6 have died (1 in LD+ASCT and 5 in LD alone). DOR, PFS and OS were not significantly different in both groups. OS showed a trend to be superior in patients treated with LD+ASCT (p=0.08). (Table 1). One patient in the LD+ASCT arm developed MDS 13 months after start of therapy. Conclusion: Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed MM patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR. There was no difference in terms of DOR or PFS with a trend of superior OS in the LD+ASCT group. The study requires careful interpretation based on the low patient number and relatively short follow up, but supports the continued role of upfront consolidative ASCT in newly diagnosed MM patients. The incidence of secondary malignancy was low with the development of 1 MDS. Updated data on response and overall survival will be available at the time of presentation. Disclosures: Roodman: Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Raptis:Millennium: Speakers Bureau; Celgene Corp: Speakers Bureau; Eisai: Speakers Bureau. Lentzsch:Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria.

scholarly journals Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study

2021 ◽  
Vol 5 (3) ◽  
pp. 725-736 ◽  
Author(s):  
Evangelos Terpos ◽  
Noopur Raje ◽  
Peter Croucher ◽  
Ramon Garcia-Sanz ◽  
Xavier Leleu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Ad Hoc ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Recent Trial ◽  
Phase 3 ◽  
Free Survival ◽  
Intent To Treat ◽  
Baseline Renal Function

Abstract An exploratory end point from a recent trial in patients with newly diagnosed multiple myeloma showed that median progression-free survival (PFS) was increased by 10.7 months with denosumab vs zoledronic acid. We performed additional analyses to identify factors that may have contributed to the favorable PFS with denosumab. Ad hoc analyses were performed for patients intending to undergo autologous stem cell transplantation (ASCT; ASCT intent), not intending to undergo ASCT (ASCT no intent), and intent-to-treat according to age (<70 or ≥70 years) and baseline renal function (≤60 mL/min or >60 mL/min creatinine clearance [CrCl]). Of 1718 patients, 930 (54.1%) were in the ASCT-intent subgroup, and 788 (45.9%) were in the ASCT-no-intent subgroup. In the ASCT-intent subgroup, frontline triplet (median PFS, not estimable vs 35.7 months; hazard ratio [HR] [95% confidence interval (CI)], 0.65 [0.47-0.90]; descriptive P = .009) or bortezomib-only (median PFS, not estimable vs not estimable; HR [95% CI], 0.61 [0.39–0.95]; descriptive P = .029) induction regimens demonstrated the strongest PFS benefit favoring denosumab vs zoledronic acid. In the ASCT-no-intent subgroup, no benefit with denosumab vs zoledronic acid was observed. PFS favored denosumab vs zoledronic acid in patients with CrCl >60 mL/min and in patients <70 years old, but no difference was observed in patients with CrCl ≤60 mL/min or patients ≥70 years old. The PFS difference observed with denosumab is one of the notable benefits reported in newly diagnosed multiple myeloma and was most pronounced in patients intending to undergo ASCT and those who received proteasome inhibitor (PI)−based triplet regimens. This study was registered at www.clinicaltrials.gov as #NCT01345019.

scholarly journals Presence of Multiple High Risk Cytogenetic Abnormalities Is Associated with Rapid Progression and Shorter Survival in Newly Diagnosed Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-23
Author(s):  
Portia Smallbone ◽  
Stephanie Clugston ◽  
Rebecca De Kraa ◽  
Duncan Purtill ◽  
Matthew Wright ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Response Rate ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Double Hit

Background: Detection of cytogenetic abnormalities by fluorescent in situ hybridization (FISH) are a critical component of diagnostic workup and prognostication in patients with multiple myeloma. Higher risk cytogenetic abnormalities are defined as t(4;14), t(14;16) and del(17p),1 with 1q21 gain more recently described, and are associated with reduced overall survival and lower response rate.2 Objectives: To ascertain the impact of presence of multiple high risk cytogenetic abnormalities, "double-hit", on clinical characteristics, response to therapy, overall and progression free survival in newly diagnosed patients with multiple myeloma. Methods: We retrospectively analyzed records of 279 patients with multiple myeloma aged over 18 years reviewed and/or treated across two tertiary hospitals (Fiona Stanley Hospital and Royal Perth Hospital) between 1st January 2008 and 31st of December 2019. Karyotyping and FISH on interphase nuclei on bone marrow cells was recorded. High risk cytogenetic abnormalities (HRC) were categorized in accordance with the International Myeloma Working Group (IMWG) definition and included deletion (17p), t(4;14) and t(14;16). Patients were categorized into three groups based on number of HRC present (HRC=0, HRC=1 and HRC>1). Results: Two hundred and thirty four patients had complete data on HRC and were included in the analysis (n=182 for HRC=0, n=44 for HRC=1 and n=8 for HRC>1). Baseline characteristics for the three groups are listed in Table 1. One or more high risk cytogenetic abnormalities (HRC) were detected in 22.2% of patients, with del(17p) and t(4;14) identified most commonly, at 10.7% and 9.3% respectively. All patients in the HRC>1 cohort had del (17p) with 62% (n=5) having concurrent t(14;16) and 38% (n=3) having t(4;14). Females were more likely to have HRC (41.2% in HRC=0 vs 68.1% in HRC=1 vs 50% in HRC=>1, p=0.0055). Patients in the HRC>1 cohort appeared to have higher ISS stage (60% stage III) however this did not meet statistical significance due to low numbers in the HRC>1 cohort. A greater proportion of patients in the HRC>1 cohort (100%) received bortezomib-based therapy (p=0.05). Overall response rate (ORR) was similar between cohorts, 84.8%, 86.0% and 71.43% in HRC=0, HRC=1 and HRC>1 respectively, p=0.95. High risk cytogenetic abnormalities were associated with a worse overall survival (OS) and progression free survival (PFS) compared to patients with standard risk disease. Median overall survival (OS) was 52, 20 and 8 months for HRC=0, HRC=1 and HRC>1 respectively, p<0.0001 Figure 1a. Median PFS was 43, 12 and 6 months for HRC=0, HRC=1 and HRC>1 respectively, p<0.0001 Figure 1b. Conclusions: Patients with multiple high risk cytogenetics, "double hit" myeloma have an exceptionally poor prognosis with earlier relapse and shorter survival than those with a single high risk abnormality. This represents a significant area of unmet need in myeloma therapy and risk adapted treatment intensification strategies need to be evaluated in clinical trials to improve outcomes in this cohort. Disclosures Leahy: Pfizer: Membership on an entity's Board of Directors or advisory committees. Sidiqi:Amgen: Honoraria; Celgene: Honoraria, Other: Travel grant; Janssen: Honoraria.

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