Melphalan, Prednisone and Lenalidomide Followed by Lenalidomide Maintenance Displays Treatment Characteristics Favourable to Global Quality of Life in Newly Diagnosed Multiple Myeloma (NDMM) Patients ≥ 65 Years,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3988-3988 ◽  
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Antonio Palumbo ◽  
Roman Hajek ◽  
Martin Kropff ◽  
Maria Teresa Petrucci ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Partial Response ◽  
Progressive Disease ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Risk Of Disease ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 3988 Background: Melphalan, prednisone and lenalidomide followed by lenalidomide maintenance (MPR-R) demonstrated higher response rates (ORR; 77% vs. 50%, p <.001; VGPR or better: 32% vs. 12%, p <.001) and significantly reduced the risk of disease progression (hazard ratio [HR] = 0.423, p <.001) vs. MP alone [Palumbo, 2010]. Alongside efficacy considerations, analyses on health-related quality of life (HRQoL) may help more fully establish a regimen's overall treatment profile. HRQoL improvements with MPR-R were observed during MPR induction as well as lenalidomide maintenance, documenting a well-balanced profile in terms of efficacy, tolerability and HRQoL [Dimopoulos, 2011]. Alternative findings on novel NDMM treatment have shown efficacy of melphalan, prednisone and bortezomib (VMP) treatment to be associated with an intermittent deterioration in patients' HRQoL [Dhawan, 2009]. Methods: A mixed effects model was developed based on parameters pre-selected as potentially clinically relevant in impacting HRQoL. Models were run on six domains pre-selected based on clinical relevance: Global QoL, Physical Functioning, Fatigue and Pain (from EORTC QLQ-C30), and Disease Symptoms and Side Effects of Treatment (from EORTC MY20). Cycle 16 was determined as the last observation time point with a statistically meaningful sample size at time of follow-up (May 2010). Following explanatory variables were included: time-dependant covariates at individual HRQoL measurement time points (i.e. cycle 4, 7, 10, 13 and 16), treatment group (MPR-R vs. MP), gender (Female vs. Male), age, baseline QoL, Partial Response (PR) vs. Stable Disease (SD) and Very Good Partial Response or better (≥VGPR) vs. SD, Progressive Disease (PD) and Discontinuation (DC). Neutropenia and anemia, both Grade 3 or 4, were considered the clinically most relevant safety parameters. Main results for Global QoL are reported, with results from other domains found to be comparable. Results: Across all time-dependant covariates, a statistically significant reduction on Global QoL (−4.63; p=.004) was observed at Cycle 4. Being female vs. male significantly reduced Global QoL by -−.07 (p=.026). Each additional life year was found to lower Global QoL b− −0.40 points (p=.034). Baseline Global QoL was also significant, each additional score point leading to +0.30 (p <.001). A response level of ≥VGPR vs. SD increased Global QoL by 9.11 (p=.023); Progressive Disease (PD) reduced Global QoL by -−.34 score points (p <.001). All other pre-defined variables did not significantly impact Global QoL. Clinically meaningful changes for Global QoL in the underlying patient population have been determined to constitute at least a 7-point change [Dimopoulos, 2011]. Progressive disease (reducing Global QoL), respectively ≥VGPR (increasing Global QoL) exerted clinically meaningful changes, as did anemia grade 3–4, which had a clinically meaningful, but not statistically significant negative impact (−9.85; p=.057). Although no significant direct effect of MPR-R over MP on Global QoL was detected in the underlying model, MPR-R displays properties which favor an improved HRQoL profile, including a stronger delay in PD and higher % of VGPR vs. MP patients. Furthermore, certain properties more frequently observed with MPR-R than MP (neutropenia grade 3 or 4 and discontinuation, DC) were shown not to have a significant impact on HRQoL. Anemia grade 3 or 4, exerted a clinically meaningful negative effect but was not significantly more often observed with MPR-R compared to MP (24% vs. 17%, p= 0.091). Conclusions: More patients achieved ≥VGPR when receiving continuous MPR-R treatment than those receiving MP. In the above pooled analysis, ≥VGPR was shown to improve Global QoL in a clinically meaningful and statistically significant way. Furthermore, progression was also shown to negatively impact Global QoL (−8.34; p <.001), with MPR-R significantly reducing the risk of disease progression over MP. Delaying progression with continuous MPR-R therefore helps to maintain a high Global QoL. Disclosures: Dimopoulos: Celgene: Consultancy, Honoraria. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma. Palumbo:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Ortho-Biotech: Honoraria. Hajek:Celgene: Honoraria; Janssen-Cilag: Honoraria; Merck: Honoraria. Petrucci:Celgene: Honoraria. Lewis:Celgene: Employment, Equity Ownership. Millar:Celgene: Consultancy. Zhang:Celgene: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. Delforge:Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Speakers Bureau.

A Phase II Study of PS-341 for Patients with High Risk, Newly Diagnosed Multiple Myeloma: A Trial of the Eastern Cooperative Oncology Group (E2A02).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2546-2546 ◽  
Author(s):  
Angela Dispenzieri ◽  
Emily Blood ◽  
David Vesole ◽  
Rafael Fonseca ◽  
Natalie Callander ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
High Risk ◽  
Partial Response ◽  
Progressive Disease ◽  
Response Rate ◽  
Cell Labeling ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Background: Multiple myeloma (MM) is an incurable disease with a anticipated overall survival (OS) ranging from months to decades. Modest improvements in OS have been made with high-dose chemotherapy with peripheral blood stem cell transplant (PBSCT), but to date prognostic factors have a greater impact on OS than do individual therapies. Patients with adverse risk factors such as elevated beta-2 microglobulin (B2M), plasma cell labeling index, deletions of the long arm of chromosome 13 by metaphase cytogenetics (del 13q) require innovative new treatment strategies. Bortezomib has significant activity in patients with both newly diagnosed and relapsed/refractory MM, but its specific role in patients with adverse features has not yet been defined. Methods: Patients with newly diagnosed “high-risk” myeloma (B2M ≥ 5.5., PCLI ≥ 1, or del 13q) and adequate organ and functional status were eligible. Patients were treated with bortezomib 1.3 mg/m2 day 1, 4, 8, and 11 every 21 days for 8 cycles as induction. After induction, patients were scheduled to receive bortezomib 1.3 mg/m2 every other week indefinitely. Elective peripheral stem cell mobilization (growth factor alone) was allowed after 4 cycles of bortezomib. Patients relapsing on maintenance schedule were to have the full induction schedule resumed. Responses were by the EBMT criteria but a very good partial response category was included. The primary end-point was the response rate in these high-risk patients (90% power to detect a response rate of 50% or higher). The study decision rule requires that 16 or more responses, among 39 eligible patients, are seen in order to declare this treatment effective. Results: Between March 15, 2004 and March 10, 2005, 44 patients enrolled on study. Among the 43 eligible patients, median age was 63; 51% were male. All patients had high risk disease: del 13q (6/41); plasma cell labeling index ≥1% (16/34); and B2M≥5.5 (34/43). Preliminary response data are available for 18 of the 44 cases enrolled, of which 7 had partial response, 1 had minimal response, 1 had no response, 2 had progressive disease, and 5 were unevaluable. Among those patients completing induction therapy and with response information, the median number of cycles of therapy administered is 5, range (0,8). The most common non-hematologic adverse events (AEs) of grade 3 or higher included hyponatremia (9 patients) and diarrhea (6 patients). Mild sensory peripheral neuropathy was common: grade 1, 16 patients; grade 2, 2 patients. Only 1 patient had grade 3 peripheral neuropathy. One patient died after receiving 2 doses bortezomib due to heart block and asystole. Two patients had a grade 4, 25 patients had grade 3, and 13 had grade 1 or 2 as the worst grade non-hematologic adverse event. Based on data received by August 1, 2005, 18 patients have gone off study: AEs (2); death (1); progressive disease (9); and other reasons (6). Updated results on the full study population along with FISH data for IgH translocations and deletions of 13q and 17p will be presented at the meeting. Conclusions: Preliminary results suggest that upfront bortezomib has activity in patients with high-risk MM, but further follow-up is required.

A Multicenter, Open-Label, Phase 1b Study of Carfilzomib, Cyclophosphamide, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients (CHAMPION-2)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3325-3325 ◽  
Author(s):  
Ralph V. Boccia ◽  
Alberto Bessudo ◽  
Richy Agajanian ◽  
Paul Conkling ◽  
Wael Harb ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Research Funding ◽  
Progressive Disease ◽  
Newly Diagnosed ◽  
Open Label ◽  
Employment Equity ◽  
Phase 1B ◽  
Equity Ownership ◽  
Dose Levels

Abstract Introduction: Carfilzomib is an irreversible second-generation proteasome inhibitor that is currently approved for the treatment of relapsed or refractory multiple myeloma (MM). The primary objective of the CHAMPION-2 study was to determine the maximum tolerated dose (MTD) of carfilzomib when used with cyclophosphamide and dexamethasone (KCyd) for newly diagnosed MM, and secondary objectives were to evaluate the overall response rate (ORR), time to response (TTR), and safety of KCyd. Methods: This was a multicenter, open-label, single-arm, phase 1b study that enrolled patients 18 years or older with newly diagnosed symptomatic MM. Patients deferring transplant and transplant-ineligible patients were allowed. Treatment was given in 28-day cycles and continued for 8 cycles, or until unacceptable toxicity, withdrawal of consent, or progressive disease. A traditional 3+3 dose escalation scheme was used to determine the MTD of carfilzomib, with the following dose levels evaluated: 36, 45, and 56 mg/m2. Carfilzomib (30-minute infusion) was administered on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle, beginning with 20 mg/m2 on days 1 and 2 of cycle 1, then stepping up to the assigned dose level. In each cycle, cyclophosphamide (oral, 300 mg/m2) was administered on days 1, 8, and 15, and dexamethasone (oral or intravenous, 40 mg) was administered on days 1, 8, 15, and 22. An expansion cohort was enrolled at the established MTD or the maximum planned dose (MPD). Results: There were no dose-limiting toxicities observed at any of the dose levels evaluated, and thus the MPD of 56 mg/m2 was brought forward into dose expansion. A combined total of 16 patients (dose escalation + dose expansion) received carfilzomib at 56 mg/m2. The median age of patients who received KCyd at 56 mg/m2 was 65 years (range, 49-81), 56.3% were male, and 93.8% had an ECOG performance status of 0 or 1. At 56 mg/m2,the ORR was 87.5% (95% CI, 61.7%-98.4%), and best overall responses were complete response (n = 1); very good partial response (n = 7); partial response (n = 6); and stable disease (n = 2). The median TTR for patients who received the 56 mg/m2 dose and achieved partial response or better was 1 month. At 56 mg/m2,the most common adverse events of any grade were nausea (68.8%), cough (62.5%), diarrhea (56.3%), anemia (50.0%), fatigue (50.0%), and headache (43.8%), and the most common grade ≥ 3 adverse events were anemia (25.0%), hypokalemia (18.8%), neutropenia (18.8%), acute kidney injury (12.5%), and decreased white blood cell count (12.5%). Any-grade peripheral neuropathy was reported for 1 patient treated with the 56 mg/m2 dose. The mean number of treatment cycles started among patients who received the 56 mg/m2 dose was 7 (range, 3-8). In total, 6 of the 16 patients who received carfilzomib at 56 mg/m2 did not complete the 8 cycles of study treatment: 1 patient discontinued due to progressive disease (which manifested during a break in treatment for renal insufficiency), 1 patient withdrew from the study, and 4 patients discontinued treatment because of adverse events. Adverse events that led to treatment discontinuation were acute renal failure (n = 1), creatinine increase and dehydration (n = 1), intermittent nausea (n = 1), and urinary tract infection (n = 1). One patient in the 45 mg/m2 cohort experienced death due to sudden cardiac arrest; no deaths in the 36 or 56 mg/m2 cohorts occurred during the study. Conclusions: Carfilzomib administered at 56 mg/m2 twice weekly in combination with cyclophosphamide and dexamethasone was effective and showed acceptable toxicity for treating patients with newly diagnosed MM. The CHAMPION-2 study suggests that KCyd may be considered for first-line treatment of MM, including for patients not eligible for transplant. Acknowledgments: This study was supported by Onyx Pharmaceuticals, Inc. an Amgen, Inc. subsidiary. The authors would like to thank Jesse Potash of Amgen, Inc. for medical writing assistance. Disclosures Boccia: Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; Gilead: Speakers Bureau; Eisai: Consultancy, Honoraria, Speakers Bureau. Conkling:USOncology Research: Research Funding; Amgen Inc.: Research Funding. Harb:Amgen Inc.: Consultancy. Yang:Amgen Inc.: Employment, Equity Ownership. Pinchasik:Amgen Inc.: Employment, Equity Ownership. Kimball:Amgen Inc.: Employment, Equity Ownership. Berenson:OncoTracker: Employment, Equity Ownership.

scholarly journals Preliminary Results from a Phase I Study of Isatuximab (ISA) in Combination with Bortezomib, Lenalidomide, Dexamethasone (VRd), and in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Non-Eligible for Transplant

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 595-595 ◽  
Author(s):  
Enrique M. Ocio ◽  
Paula Rodriguez Otero ◽  
Sara Bringhen ◽  
Stefania Oliva ◽  
Axel Nogai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Board ◽  
Induction Phase ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background: Isatuximab (ISA) is an anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells via direct tumor targeting and immune cell engagement. ISA, combined with bortezomib, has demonstrated strong potentiation in a multiple myeloma (MM) xenograft model (Clin Cancer Res 2014:20:4754). This supported evaluation of ISA with bortezomib combinations in pts with newly diagnosed multiple myeloma (NDMM) ineligible for transplant. In the initial cohort, ISA combined with bortezomib, cyclophosphamide, and dexamethasone (dex) was well tolerated with 73% of pts achieving very good partial response (VGPR) or better and 40% with complete response (CR) (Blood 2017; 130: 3160). The combination of bortezomib, lenalidomide, and dex (VRd) is also effective in NDMM (Lancet 2017:389:519-27). Here, we report initial data from a Phase Ib study of ISA plus VRd in pts with NDMM (NCT02513186). Methods: Pts with NDMM ineligible for transplantation were treated in 2 phases: induction and maintenance. Induction phase (four 6-week cycles [C]): ISA (10 mg/kg) on Day (D) 1, 8, 15, 22, 29 (C1), followed by D1, 15, 29 (C2-4); bortezomib (1.3 mg/m2) on D1, 4, 8, 11, 22, 25, 29, 32 (C1-4); lenalidomide (25 mg/day): D1-14 and D22-35 (C1-4); dex (20 mg/day): D1, 2, 4, 5, 8, 9, 11, 12, 15, 22, 23, 25, 26, 29, 30, 32, 33. Maintenance phase (4-week cycles): ISA (10 mg/kg) on D1, 15 (all cycles); lenalidomide (25 mg/day): D1-21 (all cycles); dex (40 mg): D1, 8, 15, 22 (all cycles), unless the pt was >75 years of age, then the dose was 20 mg. The primary objective was to evaluate safety and preliminary efficacy (overall response rate [ORR] and CR rate, [IMWG criteria]) of ISA plus VRd. Minimal residual disease (MRD) was evaluated using next generation sequencing (NGS) and flow cytometry (NGF) at a sensitivity of 10-6 in pts achieving VGPR or above. Here, we report results from a protocol-planned interim analysis. Results: All 22 pts were included in the safety analysis (pts who received ≥1 dose of ISA) and 14 were eligible for preliminary efficacy analyses (first 14 pts who completed the 4 induction cycles). Median age was 71 (range 63-77) years. At study entry, 6, 12, and 1 pt were International Staging System Stage I, II, and III, respectively. One pt had extramedullary plasmacytoma at baseline. At data cut-off (Mar 22, 2018), the median number of cycles was 5.5 (1-9). Three pts discontinued treatment (2 VGPR, 1 not efficacy-evaluable): 2 pts due to adverse event (AE); Grade (Gr) 3 infusion reaction (IR) (ISA-related; Gr 3 dyspnea, Gr 2 glottic edema, Gr 2 nasal edema, and Gr 2 generalized rash), and Gr 5 bacteremia (lenalidomide- and dex-related); and 1 pt withdrew consent; 19 (86%) pts are continuing treatment. Dose reduction of bortezomib, lenalidomide, and dex was required in 6 (29%), 4 (16%), and 5 (28%) pts, respectively. TEAEs occurred in 19 (86%) pts. Most frequent TEAEs (any Gr; excluding laboratory abnormalities) were constipation (10 pts [46%]), IRs and peripheral edema (9 pts [41%] each), asthenia, diarrhea, and peripheral sensory neuropathy (8 pts [36%] each), hypotension (7 pts [32%]), fatigue and respiratory tract infection (6 pts [27%] each), cough and dyspnea (5 pts [23%] each). Gr ≥3 AEs were reported in 10 (46%) and serious AEs (SAEs) in 4 (18%) pts. Treatment-related SAEs occurred in 2 (9%) pts (IR and pancreatitis). IRs were Gr 1/2 in all but 1 (5%) pt (Gr 3). Gr 3/4 laboratory hematologic abnormalities: lymphopenia (8/22), neutropenia (4/22), thrombocytopenia (4/22)VGPR, 1 partial response (PR) and 1 pt with stable diseaseMedian time to first response was 1.4 months (end of C1) and, with a median follow-up of 7.49 months (at cut-off date), no pt has progressed, with all except 3 pts continuing on therapy. Five (38.5%) of 13 pts achieved MRD-negative status (by NGF and NGS, or NGS only). Conclusion: These data suggest that ISA plus VRd followed by ISA plus Rd is well tolerated with a high ORR of 93%. All responders had VGPR or CR except 1 pt with PR. Quality of CR may have been underestimated due to ISA interference which could be resolved with an interference assay. Funding: Sanofi Disclosures Ocio: Janssen: Consultancy, Honoraria; AbbVie: Consultancy; BMS: Consultancy; Pharmamar: Consultancy; Takeda: Consultancy, Honoraria; Seattle Genetics: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Sanofi: Research Funding; Mundipharma: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Array Pharmaceuticals: Research Funding. Rodriguez Otero:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Janssen: Consultancy, Honoraria; Clínica Universidad de Navarra: Employment; Bristol Myers Squibb: Research Funding. Bringhen:Amgen: Honoraria, Other: Advisory Board; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria, Other: Advisory Board; Takeda: Consultancy. Oliva:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Attal:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janseen: Consultancy, Research Funding; Sanofi: Consultancy. Moreau:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kanagavel:Sanofi: Employment, Equity Ownership. Fitzmaurice:Sanofi: Employment, Equity Ownership. Wu:Sanofi: Employment, Equity Ownership. Martinez Lopez:Janssen: Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau.

scholarly journals A Phase 1b Study of Oprozomib with Dexamethasone or Pomalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 803-803 ◽  
Author(s):  
Parameswaran Hari ◽  
Mark A. Schroeder ◽  
James R Berenson ◽  
Andrzej Jakubowiak ◽  
Jonathan L Kaufman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Board Of Directors ◽  
Research Funding ◽  
Objective Response ◽  
Employment Equity ◽  
Advisory Committees ◽  
Phase 1B ◽  
Equity Ownership ◽  
Grade 3

Abstract Introduction: Oprozomib is a selective oral tripeptide epoxyketone inhibitor of the chymotrypsin-like subunit of the constitutive proteasome and immunoproteasome. This phase 1b study evaluated the safety and tolerability of two new formulations of oprozomib in combination with dexamethasone (Odex) or pomalidomide and dexamethasone (OPomD) in patients with relapsed or refractory multiple myeloma (RRMM). Methods: Adult patients with RRMM who had received at least 2 prior lines of therapy and whose prior treatment included both lenalidomide and a proteasome inhibitor were eligible for inclusion. Patients received either immediate-release (IR) or extended-release gastroretentive (GR) oprozomib, orally, in combination with dexamethasone (20 mg) alone or pomalidomide (4 mg) and dexamethasone (20 mg) in 4-week cycles. Oprozomib was given according to a 2/7 schedule on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 4-week cycle. In part 1 of the study, patients received Odex with either IR oprozomib at 150 mg/day or GR oprozomib at 150 mg/day. In part 2 of the study, patients received OPomD at increasing dose levels. Dosing for the IR formulation began at 150 mg/day and could be increased to 300 mg/day in increments of 25 mg as needed; at least one cohort could be enrolled at each dose level of oprozomib. Dosing for the GR formulation was determined based on the efficacy and safety data observed in the initial IR dose escalation and was at least one dose level lower than the highest dose tested of the IR formulation. The primary objectives of the study were to identify the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of the OPomD formulations. Results: Overall, 34 patients were assessed at the time of this analysis. Baseline patient demographics and disease characteristics are shown in Table 1. Fourteen patients (41%) received prior carfilzomib, and 10 of these were carfilzomib-refractory; 27 patients (79%) received prior bortezomib and 14 were bortezomib-refractory. Patients were enrolled into 6 cohorts and received either IR 150 mg/day (n=5) or GR 150 mg/day (n=8) Odex, or IR 150 mg/day (n=4), IR 200 mg/day (n=8), IR 225 mg/day (n=5), or GR 150 mg/day (n=4) OPomD. Median (interquartile range) number of cycles of oprozomib received for each cohort was 2.0 (1.0-11.0), 3.5 (1.5-4.0), 6.5 (2.5-9.5), 4.5 (3.0-5.5), 1.0 (1.0-1.0), and 2.0 (1.5-2.0), respectively. Three patients experienced dose-limiting toxicities (IR 150 mg/day OPomD, increased lipase; IR 200 mg/day OPomD, acute kidney injury; GR 150 mg/day OPomD, febrile neutropenia). At the time of this analysis the MTD was not yet reached for either the IR or GR formulation. Most patients (97%) experienced ≥1 treatment-emergent adverse event (AE) and 23 (68%) experienced ≥1 treatment-emergent grade ≥3 AE. AEs that occurred in ≥50% of patients in any cohort are listed in Table 2; the most common overall were nausea (62% any grade; 3% grade ≥3), diarrhea (50% any grade; 6% grade ≥3), and vomiting (47% any grade; 6% grade ≥3). Four patients (12%) experienced treatment-emergent AEs leading to discontinuation of study drug; no fatal AEs occurred. Seven patients who received OPomD had an objective response at the time of this analysis (IR 150 mg/day, n=1 [33%], median duration of response [DOR]=169 days; IR 200 mg/day, n=6 [67%], median DOR=86.5 days; DOR assessments ongoing). Of the seven patients with an objective response, six had a partial response (IR 150 mg/day and IR 200 mg/day) and one had a very good partial response (IR 200 mg/day). Progression-free survival data were not yet mature. In total, 16 of 34 patients continue to receive oprozomib therapy. The results reported are based on preliminary data available at the time of analysis. The study is ongoing and updated results will be provided at the meeting. Conclusion: Results from this study showed that treatment with OPomD had manageable toxicity in patients with RRMM. The most common AEs observed were gastrointestinal disorders, and most of these were grade 1-2 with no gastrointestinal bleeding reported. Furthermore, OPomD therapy showed promising efficacy, with an objective response rate of 67% for patients in the IR 200-mg/day cohort. Disclosures Hari: Sanofi: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen Inc.: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Spectrum: Consultancy, Research Funding. Schroeder:Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Berenson:Amgen Inc.: Consultancy, Honoraria, Research Funding. Jakubowiak:Takeda: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; SkylineDx: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Kaufman:BMS: Consultancy; Roche: Consultancy; Abbvie: Consultancy; Karyopharm: Other: data monitoring committee; Janssen: Consultancy. Voorhees:Amgen Inc.: Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TeneoBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Novartis: Consultancy, Other: served on an IRC. Fujii:Amgen Inc.: Employment, Equity Ownership. Yang:Amgen Inc.: Employment, Equity Ownership. Galimi:Amgen Inc.: Employment, Equity Ownership.

Continued Treatment Duration, Drug dosing  and Health-Related Quality Of Life (HRQoL) Of Patients With Relapsed/Refractory Multiple Myeloma (RRMM) Receiving 2nd and 3rd Line Treatments: Results From a European Multicentre Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5368-5368
Author(s):  
Maria Teresa Petrucci ◽  
Xavier Leleu ◽  
Charalampia Kyriakou ◽  
Isabelle Vande Broek ◽  
Philip T Murphy ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Final Visit ◽  
Employment Equity ◽  
Advisory Committees ◽  
Multicenter Observational Study ◽  
Related Quality ◽  
Health Related ◽  
Equity Ownership

Abstract Introduction The use of novel therapeutic agents has significantly improved both progression-free and overall survival in multiple myeloma (MM) patients. In this context, evaluating health-related quality of life (HRQoL) gains in importance. The objective of this analysis is to explore patients’ HRQoL associated with 2nd and 3rdline treatments for Relapsed/Refractory MM (RRMM) and to compare HRQoL in those patients that completed 6 months of treatment vs. patients who discontinued from the study earlier. Methods A multicenter observational study is being conducted in 34 sites in Italy, Germany, France, UK, Ireland and Belgium in RRMM patients starting 2nd or 3rd line bortezomib- or lenalidomide-based treatment. HRQoL and symptoms of patients are assessed at baseline, month 3, and month 6 or discontinuation visit using two EORTC questionnaires: 1) Quality-of-Life Core Questionnaire (QLQ-C30) including 15 domains (Global Health Status/QoL, Physical, Role, Emotional, Cognitive and  Social Functioning; Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea and Financial Difficulties); 2) and QLQ-Multiple Myeloma (QLQ-MY20) including four domains (Disease Symptoms, Side Effects of Treatment, Body Image and Future Perspective). All EORTC scores range 0-100. Higher HRQoL scores indicate better HRQoL, higher symptom scores indicate worse symptoms. Descriptive statistics and paired t-tests were used in this interim analysis to evaluate changes in scores from baseline. Results As of June 2013, 206 patients (mean age: 69; 51% male) were enrolled in the study and included in this interim analysis. The average time since diagnosis was 3.4 years, with 90% of patients starting 2nd line and 10% starting 3rdline treatment. Overall, EORTC questionnaires were completed by 197, 130, 84 and 34 patients at baseline, month 3, month 6 and discontinuation, respectively. A total of 84 patients received bortezomib and 117 received lenalidomide. Out of 84 bortezomib patients, 54 had already completed their final visit, split about evenly between month 6 (29 patients) and early discontinuation (25 patients, 46%). Out of 117 lenalidomide patients, 64 had completed their final visit assessment, 55 with continued treatment until month 6 and nine patients discontinuing earlier (14%). A substantial and often clinically meaningful decline in HRQoL (Minimal Important Difference, MID > 6, based on 1 standard error measurement, SEM, as calculated from study patients’ baseline QoL), was observed within the patient group discontinuing treatment (see Table 1). The average dosage of lenalidomide treatment was 17.0 mg/day. Bortezomib patients received vial injections at an average of 1.2 mg/m2/day, close to the pre-specified starting dose of 1.3 mg/m2/day. Bortezomib patients who discontinued early had an average number of 3.2 vials per cycle (closer to bi-weekly dosing) and continuers up to month 6 an average of 2.3 vials per cycle, closer to weekly dosing. Conclusions First results of this multicenter observational study show a strong association between treatment discontinuation and HRQoL in RRMM. While HRQoL is maintained in patients who pursue treatment, early treatment discontinuation is significantly associated with worsened HRQoL. Higher discontinuation rates were observed amongst bortezomib treated patients as compared to lenalidomide treated patients.  A direct comparison by treatment group will be performed when final data is available. Disclosures: Petrucci: Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Leleu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Leopharma: Consultancy, Honoraria; Millennium : Honoraria; Amgen: Honoraria; Novartis: Honoraria. Lewis:Celgene GmbH : Employment, Equity Ownership. Bacon:Celgene International : Employment, Equity Ownership. Arnould:Celgene: Consultancy. Welslau:Celgene: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Comprehensive Geriatric Assessment in Consecutive Newly-Diagnosed Elderly Multiple Myeloma Patients in China: A Multicentered, Prospective, Non-Interventional Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5493-5493
Author(s):  
Yuan Yao ◽  
Dehui Zou ◽  
Aijun Liao ◽  
Xiaoxia Chu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Geriatric Assessment ◽  
Real World ◽  
Comprehensive Geriatric Assessment ◽  
Newly Diagnosed ◽  
Frail Patients

Background: Multiple Myeloma (MM) is a disease of the elderly, whose prognoses are highly heterogeneous. Hence International Myeloma Working Group (IMWG) proposed geriatric assessment (GA) in 2015, including daily activity and comorbidity status, to better discriminate between fit and frail patients (Palumbo et al, 2015). However, IMWG recruited patients from clinical trials instead of real world practices. Therefore we studied GA in elderly MM patients consecutively in China, along with other perspectives which are known to be problematic in elderly population that were previously left unnoticed, such as nutrition status, risk of cognitive impairment, risk of depression, and quality of life. Aim: Our study centers on the feasibility to perform a more comprehensive geriatric assessment (cGA) in elderly MM patients, current cGA status in elderly MM patients in China, and the cGA difference between Chinese patients and patients in the IMWG study. Method: From August 2017 to April 2019, we continuously recruited 336 newly diagnosed elderly (age ≥ 65) MM patients from 21 centers in China. cGA was performed at diagnosis, after treatment cycle 1, after cycle 4, and 1 year after treatment. cGA includes physical conditions (ECOG), activities of daily living (ADL), instrumental ADL (IADL), mini-nutritional assessment (MNA-SF), geriatric depression scale (GDS), mini-mental state examination (MMSE), quality of life (SF-36) and Charlson comorbidity index (CCI). Staging was assessed at baseline (International Staging System (ISS) & Revised ISS) and hematological responses were evaluated along with each cGA timepoint. Results: We pool-analyzed data of 336 newly-diagnosed elderly MM patients. The median age was 70 (range 65-88) and 25.5% of patients were older than 75 years. 336 (100%) patients were able to complete cGA, and median assessment time was 40 minutes (range 20-70). Upon diagnosis, only 34% and 37.5% of patients had full ADL and IADL respectively. 38.5% of patients had moderate to high risk of depression (GDS ≥ 6). 13.2% of patients were malnourished (MNA-SF ≤ 7), while 46.3% of patients were at risk of malnutrition (8 ≤ MNA-SF ≤ 11). 41% of patients had at least one comorbidity (CCI ≥ 1). 45.7% of patients had moderate to intermediate risk of cognitive impairment (MMSE ≤ 26). Grouping by IMWG-GA index, our study identified 59.9% patients in frail group (vs 39% in IMWG study), 15.8% in intermediate (vs 31% in IMWG) and 24.3% in fit (vs 30% in IMWG). 69% of patients received proteasome inhibitor-containing regimens and 20.7% of patients received lenalidomide-containing regimens. Best hematological responses in fit and intermediate groups were better than responses in frail group (≥ PR rate: 88.5% in fit, 94.4% in intermediate vs 77.5% in frail). Median follow up time was 10 months. To date, 215 (64%) patients have finished the cGA after cycle 1; 164 (48.8%) patients have finished the cGA after cycle 4; 91 (27.1%) patients has finished all 4 planned cGA and improvements in cGA were observed in the majority of these patients. Conclusion: Our study showed significant CGA heterogeneity in elderly MM patients. Even in the IMWG-GA "fit" group, nutrition, depression and cognitive impairment remain problems. Frail patients took up a larger proportion in Chinese elderly MM patients compared to IMWG study. Our study strongly justifies the necessity for cGA in elderly patients with MM, more so in the real world MM patients than in the clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial

2020 ◽  
pp. JCO.20.01370
Author(s):  
Aurore Perrot ◽  
Thierry Facon ◽  
Torben Plesner ◽  
Saad Z. Usmani ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Phase Iii ◽  
Life Questionnaire ◽  
Newly Diagnosed ◽  
European Organization ◽  
Quality Of Life Questionnaire ◽  
Depth Of Response ◽  
Descriptive System

PURPOSE To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score. CONCLUSION D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.

A352 Impact of Complete Response on Quality of Life in Newly Diagnosed Multiple Myeloma Patients

2009 ◽  
Vol 9 ◽  
pp. S58 ◽  
Author(s):  
R Dhawan ◽  
J Meunier ◽  
A Regnault ◽  
D Robinson ◽  
K Rosa ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Complete Response ◽  
Newly Diagnosed

A Phase I Study of Bendamustine Combined with Lenalidomide and Dexamethasone in Patients with Refractory or Relapsed Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1856-1856 ◽  
Author(s):  
Suzanne Lentzsch ◽  
Amy O’Sullivan ◽  
Silvana Lalo ◽  
Carrie Kruppa ◽  
Diane Gardner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Board Of Directors ◽  
Dose Level ◽  
Research Funding ◽  
Advisory Board ◽  
Clinical Activity ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 1856 Poster Board I-882 Background: Lenalidomide is an analog of thalidomide that has shown significant clinical activity in patients with relapsed or refractory multiple myeloma (MM), both as a single agent and in combination with dexamethasone. Bendamustine is a bifunctional alkylating agent that is approved for the treatment of chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma that has progressed during or relapsed within 6 months following a rituximab-containing regimen. Bendamustine combined with lenalidomide may be an effective treatment option for MM patients, particularly those with preexisting or bortezomib-induced neuropathy. Our primary objective was to determine the maximum tolerated dose (MTD) and safety profile of bendamustine and lenalidomide when administered with dexamethasone for patients with relapsed or refractory MM. Methods: Patients aged ≥18 years with confirmed, measurable stage 2 or 3 MM that was refractory to or progressed after 1 or more prior therapies, including lenalidomide, received bendamustine by intravenous infusion on days 1 and 2, oral lenalidomide on days 1–21, and oral dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle. Treatment was continued until a plateau of best response, as determined by the IBMTR/ABMTR, was reached. Study drug doses were escalated through 4 levels (Table), with 3–6 patients enrolled at each level depending on the rate of dose-limiting toxicity (DLT). After determining the MTD, up to an additional 12 patients will be enrolled in an MTD expansion arm to better evaluate toxicity and clinical activity. Secondary endpoints included preliminary efficacy, as evidenced by objective response, time to disease progression, and overall survival. Results: To date, 11 patients have been enrolled, with a median age of 63 years (range, 38–75 years). The MTD of bendamustine and lenalidomide has not been identified at this point; currently, patients are enrolling on dose level 3 with 100 mg/m2 bendamustine and 10 mg lenalidomide. Thus far, DLT included 1 grade 4 neutropenia at dose level 2. Nine of 11 patients are currently eligible for response assessment. A partial response was observed in 67% of patients, including 1 very good partial response and 5 partial responses (PR). Two patients experienced stable disease and 1 exhibited progressive disease. Grade 3/4 adverse events included grade 3 neutropenia, thrombocytopenia, anemia, hyperglycemia, and prolonged QTC, and 1 grade 4 neutropenia. Conclusions: Bendamustine, lenalidomide, and dexamethasone form a well-tolerated and highly active regimen even in heavily pretreated MM patients, with a PR rate of 67%. Additional updates on response and MTD will be available at the time of presentation. Disclosures: Lentzsch: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cephalon: Consultancy, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Bendamustine is not FDA approved for the treatment of multiple myeloma in the USA. Burt:Millennium: Honoraria; Celgene: Honoraria. Mapara:Resolvyx: Consultancy, Research Funding; Genzyme: Membership on an entity's Board of Directors or advisory committees; Gentium: Equity Ownership; Celgene: Spouse is consultant , has received research funding, and participates on advisory board; Cephalon: Spouse has received funding for clinical trial and participates on advisory board. Redner:Biogen: Equity Ownership; Wyeth: Equity Ownership; Glaxo-Smith-Kline: Equity Ownership; Pfizer: Equity Ownership; Genzyme: Membership on an entity's Board of Directors or advisory committees. Roodman:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy; Acceleron: Consultancy. Zonder:Amgen: Consultancy; Pfizer: Consultancy; Cephalon: Consultancy; Millennium: Consultancy, Speaking (CME only); no promotional talks.

Sign in / Sign up

Export Citation Format

Share Document