scholarly journals A US Budget Impact Model for Selinexor in Combination with Dexamethasone for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5824-5824
Author(s):  
Ian Gould ◽  
Jan Bassali ◽  
Jyotsna Mehta ◽  
Jatin Shah ◽  
Dee Dee Mladsi
Keyword(s):  
Multiple Myeloma ◽  
Health Plan ◽  
Budget Impact ◽  
Employment Equity ◽  
Cancer Society ◽  
Refractory Multiple Myeloma ◽  
Number Of Patients ◽  
Equity Ownership ◽  
Budget Impact Model ◽  
The Cost

BACKGROUND: Multiple myeloma is a relatively uncommon hematological cancer that occurs when the bone marrow produces malignant plasma cells that enter the blood stream. In the United States, the lifetime risk of getting multiple myeloma is 1 in 132 (0.76%). American Cancer Society estimates that about 32,110 new cases will be diagnosed and about 12,960 deaths are expected to occur among multiple myeloma patients. (American Cancer Society. Cancer Facts and Figures 2019). An increasing number of treatments are available for multiple myeloma, however, due to the highly refractory nature of the disease surviving patients must eventually resort to best supportive care (BSC). Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) for the treatment of relapsed or refractory multiple myeloma (RRMM). OBJECTIVE: To estimate the budget impact of Selinexor in combination with dexamethasone (Sel-dex) for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody in US. METHOD: An interactive budget impact model was developed to evaluate the addition of Selinexor for treatment of RRMM using a hypothetical health plan of 25 million lives over a time horizon of 3-years (2019-2021) after the introduction of Selinexor. The model compares the formulary without Selinexor to a formulary with Selinexor and considers direct cost only. The model was developed following guidelines from the International Society for Pharmacoeconomics and Outcomes Research. The key assumptions in the model are that there is no reasonable alternative to Selinexor besides BSC, the use of Selinexor will not meaningfully reduce the cost of BSC, and the number of patients eligible to receive Selinexor is expected to remain the same for each of the 3 years evaluated in the model. The assumed uptake rates for Selinexor were included. The average per-person drug cost for each year of treatment is calculated by accounting for the cost of the drug including dosage, frequency, and duration of treatment. The costs of treatment-emergent adverse events occurring at grade 3 or higher occurring in at least 5% of patients in the STORM trial (NCT02336815) were included. As Sel-dex is taken orally, wastage was not considered for this model. Total annual treatment costs included drug costs, AE costs, and BSC costs, and were calculated for each scenario to estimate the budget impact of making Selinexor available as a treatment for eligible patients. One-way sensitivity analysis was conducted to test the robustness of the model results and the sensitivity of the results to uncertainty in key model input parameters including time on treatment with Selinexor (weeks), uptake of Selinexor in year 1 after market entry and the drug cost of Selinexor. Results were calculated in terms of total plan, per-member-per-month (PMPM), and per-treated-member-per-month costs. RESULTS: In the hypothetical health plan of 25 million lives, the annual number of patients eligible for Selinexor was estimated to be 182. After the adoption of Selinexor, the base case results showed minimal budget impact with $0.01 per member per month incremental cost for year 1 and $0.02 for both year 2 and year 3. For Commercial and Medicare patients, the incremental cost was < $0.02 per member per month for all three years. CONCLUSION: The results indicated that with limited treatment options in the later lines, Sel-dex for the treatment of multiple myeloma will have a minimal budget impact for a US health plan. Disclosures Gould: RTI International: Employment. Bassali:Karyopharm Therapeutics: Employment, Equity Ownership. Mehta:Karyopharm Therapeutics: Employment, Equity Ownership; Sanofi: Equity Ownership; Alkermes: Equity Ownership. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Mladsi:RTI International: Employment.

Patterns of Total Costs of Care for Newly Diagnosed Multiple Myeloma (MM) Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2656-2656
Author(s):  
Steven R. Arikian ◽  
Dejan Milentijevic ◽  
Gary Binder ◽  
Mara Silvia Monzini ◽  
X Henry Hu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Direct Costs ◽  
Drug Costs ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Monthly Total ◽  
Equity Ownership ◽  
The Cost ◽  
Over Time

Abstract Introduction: As clinical evidence has mounted in support of novel agents and longer treatment (Tx) durations for patients (pts) with newly diagnosed multiple myeloma (NDMM), questions have arisen regarding the economic impact of extending time to progression (TTP) in these pts, and the cost consequences once pts relapse and move to a second line of Tx. Previous analysis showed that relapsed myeloma pts incurred higher monthly costs once they advanced to later lines of Tx (Gaultney, 2013). There is limited information on the cost patterns of MM pts before and after their first relapse. A claims analysis was performed to evaluate the patterns of total direct costs of care, from Tx initiation until progression, for NDMM patients and for newly relapsed patients treated with novel agents, utilizing time to next therapy (TTNT) as a proxy measure for progression. Methods: A retrospective study was conducted using a large US medical and pharmacy claims database, covering > 25 million lives annually. NDMM patients were identified with at least 2 outpatient claims or 1 inpatient medical claim associated with a diagnosis of MM (ICD-9-CM] code 203.0X), with the first such claim used to define the index date. Inclusion criteria required a minimum of 12 months' pre-index enrollment and 6 months' post-index continuous enrollment between 2006 and 2012. Pts with claims for stem cell transplantation (SCT) were excluded, to avoid confounding results from various factors based on timing, costs, and site of care of SCT. The analysis focused on NDMM and relapsed MM pts receiving lenalidomide (LEN)- or bortezomib (BORT)- based Tx, where complete claim history was available from Tx onset to initiation of subsequent Tx. Using methods similar to those described by Gaultney, patients' average monthly costs were determined, including medical (inpatient, ambulatory, and emergency room) and pharmacy (index and other drugs) costs, and total cost patterns over quarterly time periods were calculated. Average Charlson comorbidity scores were determined to compare baseline measures between pt groups. Results: 897 NDMM pts and 280 relapsed MM pts were identified with complete data through initiation of subsequent Tx. Monthly total direct costs for NDMM pts were $15,400 in the first 3 months (mos) of Tx, and declined each quarter, reaching approximately $5,000/mo at 18+ mos. At relapse, monthly costs increased to over $12,000 for the first 3 mos and followed a quarterly pattern of reduction similar to that seen for NDMM pts (Fig 1). Quarterly cost reduction patterns were consistent for patients treated with LEN or BORT for both NDMM and relapsed pts. Pts' total monthly NDMM costs over the full TTNT period averaged $8,942 with LEN vs. $11,139 for BORT (due to 54% higher monthly medical costs for BORT), while monthly drug costs were nearly identical (Table 1). The baseline Charlson comorbidity index was similar between Tx groups in both lines of Tx. Figure 1: Direct monthly costs (medical and pharmacy) for LEN- and BORT-based treatments Figure 1:. Direct monthly costs (medical and pharmacy) for LEN- and BORT-based treatments Table 1: Direct monthly costs for NDMM pts Table 1 Table 1. Conclusions: For a population of NDMM pts receiving either LEN- or BORT-based Tx without SCT, followed until TTNT, total direct monthly costs per pt declined steadily over time, decreasing by 68% from the initial quarter to the period post 18 mos. Costs spiked when pts began 2nd-line therapy, then followed a similar pattern of decline over time. This pattern may suggest that further extending the TTP for NDMM pts may also yield economic benefits for each month extended before relapse. Patterns of cost decline were similar between the LEN and BORT groups, for NDMM and for relapsed patients, although mean monthly total costs were lower for NDMM pts receiving LEN-based Tx due to lower medical costs and similar drug costs. Disclosures Arikian: Genesis Research: Consultancy. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma patients . Milentijevic:Celgene Corporation: Consultancy. Binder:Celgene Corporation: Employment, Equity Ownership. Monzini:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment. Nagarwala:Celgene Corporation: Employment. Hussein:Celgene Corporation: Employment. Corvino:Genesis Research LLC: Consultancy. Surinach:Genesis Research LLC: Consultancy. Usmani:Celgene Corporation: Consultancy, Honoraria, Research Funding; Millennium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Array BioPharma: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding.

MM-008: A Phase 1 Trial Evaluating Pharmacokinetics and Tolerability of Pomalidomide + Low-Dose Dexamethasone in Patients with Relapsed or Refractory and Refractory Multiple Myeloma and Renal Impairment

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4730-4730 ◽  
Author(s):  
Jeffrey Matous ◽  
David S Siegel ◽  
Sagar Lonial ◽  
R. Donald Harvey ◽  
Claudia Kasserra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Research Funding ◽  
Platelet Transfusion ◽  
Low Dose ◽  
Phase 1 ◽  
Employment Equity ◽  
Refractory Multiple Myeloma ◽  
Equity Ownership

Abstract Background: Pomalidomide (POM) is indicated for patients (pts) with relapsed or refractory multiple myeloma (RRMM) who received ≥ 2 prior therapies including lenalidomide and bortezomib and demonstrated progression on or within 60 days of completion of the last treatment (Tx). Renal impairment (RI) is a common comorbidity of multiple myeloma (MM) occurring in 20% to 40% of pts (Eleutherakis-Papaikovou, et al. Leuk Lymphom, 2007; Knudsen, et al., Eur J Haematol, 2000). POM is extensively metabolized, with < 5% eliminated renally as the parent drug (Hoffmann, et al., Cancer Chemother Pharmacol, 2013). POM in combination with low-dose dexamethasone (LoDEX) has shown efficacy in pts with RRMM and moderate RI (creatinine clearance [CrCl] < 30-44 mL/min), but pts with severe RI (CrCl < 30 mL/min; serum creatinine> 3 mg/dL) were excluded from most trials (Siegel, et al., Blood. 2012; Weisel, et al., J Clin Oncol, 2013). MM-008 is a multicenter, open-label, phase 1 study assessing the pharmacokinetics (PK) and safety of POM + LoDEX in pts with RRMM and normal or severely impaired renal function. Methods: Pts withRRMM (≥ 1 prior Tx) and normal kidney function or mild RI (creatinine clearance [CrCl] ≥ 60 mL/min; Cohort A—control arm), severe RI (CrCl < 30 mL/min) not requiring dialysis (Cohort B), and severe RI requiring dialysis (Cohort C) were eligible. Cohort A received POM 4 mg, and Cohort B received POM 2 or 4 mg on days 1-21 of a 28-day cycle, following a 3 + 3 dose-escalation design. Cohort B results informed the 4 mg dosing of Cohort C. All cohorts received DEX 40 mg (20 mg for pts aged > 75 yrs) on days 1, 8, 15, and 22. Tx continued until progression or unacceptable toxicity. Dose-limiting toxicities (DLTs) were defined as any of the following: grade (Gr) 4 neutropenia, febrile neutropenia, Gr 4 thrombocytopenia that is a ≥ 30% decrease in platelets from baseline and requires > 1 platelet transfusion, Gr 3 thrombocytopenia with significant bleeding (requiring hospitalization and/or platelet transfusion), Gr 4 infection, or ≥ Gr 3 other non-hematologic toxicity related to POM. Serial plasma samples were analyzed to generate PK parameters. Updated PK and AE data for all cohorts will be presented. Results: As of July 17, 2014, updated data for 16 treated pts were available (8 in Cohort A; 3 in Cohort B at 2 mg; 4 in Cohort B at 4 mg; and 1 in Cohort C). Median age was 67 yrs (range, 46-76 yrs), 56% were male, all had Eastern Cooperative Oncology Group performance status 0 or 1, and a median time from diagnosis of 3.8 yrs (range, 0.6-12.5). No DLTs in cycle 1 were reported for any cohort. The most common Gr ≥ 3 adverse events (AEs) were neutropenia, anemia, infection, and fatigue (Table). Median relative dose intensity was consistent across cohorts: 90% (Cohort A), 90% (Cohort B; 2 mg), 100% (Cohort B; 4 mg) and 100% (Cohort C). Three pts discontinued due to AEs (2 in Cohort A and 1 in Cohort B 4 mg); no deaths have occurred during treatment phase. Conclusion: MM-008 is an ongoing trial prospectively evaluating the PK and safety of POM + LoDEX in pts with RRMM and severe RI. Preliminary PK data support mean dose-normalized exposure in pts with RRMM being similar between those with severe RI and those with no or mild RI at the clinical dose of 4 mg; early tolerability data (after one cycle) are encouraging. Table Cohort A(n = 8) Cohort B(n = 3) Cohort B(n = 4) Cohort C(n = 1) Cohort Characteristics POM dose 4 mg 2 mg 4 mg 4 mg CrCl (mL/min) ≥ 60 mL/min < 30 mL/min without dialysis < 30 mL/min without dialysis < 30 mL/min with dialysis Safety Dose-limiting toxicities (n) N/A 0 0 0 Grade 3/4 AEs (n) Neutropenia 4 2 1 0 Anemia 3 1 2 0 Infection 3 2 0 0 Fatigue 2 0 0 0 N/A: Not applicable (4 mg POM is approved dose for population) Disclosures Matous: Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Siegel:Celgene Corp: Honoraria, Speakers Bureau; Onyx: Honoraria, Speakers Bureau; Millennium: Honoraria, Speakers Bureau. Lonial:Onyx: Consultancy; BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Millennium: Consultancy. Harvey:Celgene Corp: Research Funding. Kasserra:Celgene Corp: Employment, Equity Ownership. Li:Celgene Corp: Employment, Equity Ownership. Chen:Celgene Corp: Employment. Doerr:Celgene Corporation: Employment. Sternas:Celgene Corp: Employment, Equity Ownership. Zaki:Celgene : Employment, Equity Ownership. Jacques:Celgene Corp: Employment, Equity Ownership. Shah:Celgene Corp: Consultancy, Research Funding.

scholarly journals Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Proteasome Inhibitor Based Therapy at First Relapse in Routine Clinical Practice in Germany

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1953-1953 ◽  
Author(s):  
H. Tilman Steinmetz ◽  
Moushmi Singh ◽  
Andrea Lebioda ◽  
Aurelien Mantonnier ◽  
Leah Fink ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Treatment Duration ◽  
Employment Equity ◽  
Available N ◽  
Median Treatment ◽  
Median Treatment Duration ◽  
Refractory Multiple Myeloma ◽  
Equity Ownership ◽  
Patient Profiles

Abstract Background: Proteasome inhibitors (PI) represent an important therapeutic advance in the treatment of patients with relapsed/refractory multiple myeloma (RRMM). In 2017, three distinct PIs (bortezomib [BTZ], carfilzomib [CFZ] and ixazomib [IXA]) were available in Germany but real-world data describing their usage was scarce. Aim: To describe characteristics and treatment experience of PI-treated patients with RRMM in Germany. Methods: A national retrospective medical chart review included consecutive patients treated with at least one dose of PI-based regimen in participating hospitals/centers across Germany between January and June 2017. The following data were extracted until April 2018 or death of patient, whichever occurred first: patient demographics, disease characteristics and treatment history at diagnosis and at initiation of PI-based therapy. Physician assessed treatment response were also collected. Results: Physicians from 44 participating centers extracted 302 patient charts, including 219 patients in 2nd line (2L) and 83 in 3rd line treatment (3L), as shown in Figure 1. Results for 2L patients are described below (Table 1, Figure 2): BTZ-treated patients represented 42% of patients (n=92) with a PI-based therapy in 2L. BTZ was often combined with dexamethasone (dex) alone (77%). Median age was 74 years and 56.5% had an ECOG status ≥2 at 2L initiation. Most patients (86%) did not receive a prior transplant. Median treatment duration was 6 months among 40 patients who completed 2L; based on 38 narratives, 2L was ended as planned (47.4%). Where response was available (n=83), 25% of patients achieved a complete response/very good partial response [CR/VGPR]. Median time to next treatment (TTnT) was 7.5 months for 12 patients who moved to 3L. Patient profiles differed in terms of prior treatment exposure: 22% of patients had been treated with a BTZ-based therapy in both 1L and 2L and 62% switched therapies from 1L lenalidomide (len) to BTZ. None of the patients receiving len in 1L were transplanted. A CR/VGPR was achieved by 65% of prior BTZ-treated patients (13/20) and 30% of patients with prior len therapy (17/57). CFZ-treated patients: 48% (n=106) of patients received CFZ-based therapy in 2L. Of those, 56% (n=59) received CFZ in combination with len/dex (KRd) and 44% (n=47) with dex alone (Kd). Median age was 68 years, 60.4% had an ECOG status of 0-1 at 2L initiation and 49% had received a transplant. In 1L, 82% had received a BTZ-based regimen. Where response was mentioned (n=89), a CR/VGPR was reached in 53% of CFZ-treated patients. Median treatment duration was 6.5 months (24/106). Based on 21 narratives, the main reason for discontinuing CFZ in 2L was disease progression (47.6%). Median TTnT was 9.5 months for 10 patients who moved to 3L. The patient profiles by KRd or Kd combination were as follows: at KRd initiation, median age was 65 years, 10.2% of patients had an ECOG status ≥2 and 72.9% were transplanted. At Kd initiation, median age was 71 years, 76.6% of patients had an ECOG ≥2 and 19.1% were transplanted. IXA-treated patients (n=21) represented only 10% of PI-treated patients in 2L. Median age was 66 years, 71.4% had an ECOG status of 0-1 at 2L initiation, 33% were transplanted, and 72% had received a BTZ combination in 1L. Information on response was premature as it was only available for 13 patients with no CR reached (VGPR 77%). Median treatment duration was 4 months (n=9) and median TTnT was 10 months for 4 patients who moved into 3L. Limitation: The main limitation of the study was the sample size of IXA-treated patients due to open inclusion criteria to select patient charts. This analysis was not powered to compare between PIs. Hence, results are descriptive of the clinical experience with PI-based therapy to date and reflect current treatment practices in Germany in 2017. Conclusion: In Germany, distinct patient characteristics are observed in clinical practice by selected PI-based therapy. Patients treated with novel PI agents in 2L are generally younger and more transplanted than bortezomib-treated patients; these appear to be important considerations when tailoring therapy in RRMM. In addition, the choice between triplet or doublet therapy for CFZ-based combinations seems to reflect prior transplant status and patients' overall functional performance. Evidence suggests that use of novel PI agents such as CFZ can translate into deeper response in 2L. Disclosures Steinmetz: Amgen, Celgene, Novartis, Vifor: Research Funding; Amgen; BMS, Celgene, Hexal-Sandoz, Medice, Novartis; Janssen-Cilag; Pharmacosmos; Pfizer, Vifor; Ariad: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion, Amgen, Bayer, Celgene, Janssen-Cilag, Novartis: Other: Travel grants. Singh:Amgen: Employment, Equity Ownership. Lebioda:Amgen: Employment, Equity Ownership. Mantonnier:Kantar Health: Employment, Other: Received funding to conduct this research. Fink:Kantar Health: Employment, Other: Received funding to conduct this research. Rieth:Amgen: Employment, Equity Ownership. Suzan:Amgen: Employment, Equity Ownership. Gonzalez-McQuire:Amgen: Employment, Equity Ownership.

scholarly journals Pmd-107: Marizomib, Pomalidomide and Low Dose-Dexamethasone Combination Study in Relapsed/Refractory Multiple Myeloma (NCT02103335): Full Enrollment Results from a Phase-1 Multicenter, Open Label Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3326-3326 ◽  
Author(s):  
Andrew Spencer ◽  
Simon Harrison ◽  
Jacob P. Laubach ◽  
Jeffrey Zonder ◽  
Ashraf Z Badros ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Low Dose ◽  
Employment Equity ◽  
Advisory Committees ◽  
Refractory Multiple Myeloma ◽  
Heavily Pretreated ◽  
Equity Ownership

Abstract Marizomib (MRZ) is a novel, irreversible, pan subunit proteasome inhibitor (PI) with preclinical evidence demonstrating in vitro and in vivo activity in multiple myeloma (MM). This study was designed to evaluate the safety and antimyeloma activity of pomalidomide (POM), MRZ and low dose dexamethasone (Lo-DEX) (PMD) in patients with relapsed and refractory multiple myeloma (RRMM). Thirty-eight heavily pretreated patients with RRMM were enrolled [dose-escalation cohort (n=14); recommended Phase 2 dose (RP2D) cohort (n=24)]. IV MRZ (0.3 to 0.5 mg/m2) was administered on Days (D) 1, 4, 8, 11; POM (3 or 4 mg) on D1 through 21; and Lo-DEX (5 or 10 mg) on D1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23 of every 28-D cycle. Patients received a median of 4 (range 1-9) prior lines of therapy; 100% received prior lenalidomide (LEN) and bortezomib (BTZ), 34% carfilzomib (CFZ), and 50% thalidomide. 53% of patients were refractory to both LEN and BTZ and 21% were refractory to LEN, BTZ, and CFZ. There were no dose limiting toxicities during the study. The most common study treatment related ≥Grade 3 adverse events (AEs) were neutropenia (11/38 pts: 29%), pneumonia (4/38 pts 11%), anemia (4/38 pts; 11%), thrombocytopenia (4/38 pts; 11%), and febrile neutropenia (2/38 pts; 5%), with two grade 4 AEs (neutropenia related to POM and viral infection related to DEX), and one grade 5 AE (cardio-respiratory arrest from a suspected PE related to POM). Overall, MRZ was well tolerated, did not add to the incidence or severity of POM/Lo-DEX AEs and the regimen may have fewer hematological and infectious AEs compared to that observed with POM/Lo-DEX. MRZ pharmacokinetic analysis revealed that it was rapidly cleared with a short T1/2 (6.2-11mins) and a large volume of distribution (41-86L) suggesting extensive tissue distribution. Pharmacodynamic analysis demonstrated rapid and robust inhibition of chymotrypsin-like activity in both packed whole blood (PWB) and peripheral blood mononuclear cells (PMBCs), reflecting the irreversible binding nature of MRZ. Evolving inhibition of trypsin-like and caspase-like proteasome activity was also observed in PWB and PBMC with continued dosing. The overall response rate (ORR) and clinical benefit rate (CBR) for the 36 response evaluable patients was 53% (19/36) and 64% (23/36), respectively (Table 1). Subpopulation analysis demonstrated an ORR of 50% (5/10) in high risk cytogenetic patients, 56% (10/18) in LEN/BTZ refractory patients, 71% (5/7) in LEN/BTZ/CFZ refractory patients and 80% (8/10) in CFZ refractory patients. These data compare favorably against POM/Lo-Dex with a near doubling of ORR in both the total patient population and the double refractory patients. Substantial activity in high-risk patients that are triple refractory and in patients that are refractory to CFZ in prior last regimen was observed. MRZ activity in RRMM patients exposed and/or refractory to multiple PIs is likely a consequence of its unique pan proteasome subunit inhibitory actions. In conclusion, MRZ in combination with POM and Lo-DEX was well tolerated and demonstrated promising activity in heavily pretreated, high-risk RRMM patients. Table 1 Table 1. Disclosures Harrison: Janssen-Cilag: Research Funding, Speakers Bureau; Celgene: Honoraria. Zonder:Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Khot:Amgen: Honoraria; Janssen: Consultancy; Pfizer: Speakers Bureau. Anderson:C4 Therapeutics: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; Oncoprep: Equity Ownership; C4 Therapeutics: Equity Ownership; Gilead: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Equity Ownership; Acetylon: Equity Ownership; Oncoprep: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. MacLaren:Triphase Accelerator: Employment, Equity Ownership. Reich:Triphase Accelerator: Consultancy. Trikha:Encycle Therapeutics: Consultancy, Equity Ownership; Triphase Accelerator: Employment, Equity Ownership. Richardson:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Dreamm-3: A Phase 3, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Monotherapy Compared with Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma (RRMM)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1900-1900 ◽  
Author(s):  
Katja Weisel ◽  
Thomas G Hopkins ◽  
Doug Fecteau ◽  
Weichao Bao ◽  
Corinne Quigley ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Research Funding ◽  
Standard Of Care ◽  
Efficacy And Safety ◽  
Open Label ◽  
Employment Equity ◽  
Phase 3 ◽  
Refractory Multiple Myeloma ◽  
Equity Ownership

Background: Belantamab mafodotin is a humanized, afucosylated, anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to monomethyl auristatin F via a maleimidocaproyl linker (mcMMAF). Upon binding to BCMA on the surface of plasma cells, it is rapidly internalized and the cytotoxic moiety (cys-mcMMAF) is released, antibody-dependent cellular cytotoxicity is enhanced, and immunogenic cell death occurs. In vitro and in vivo cytotoxic activity against both myeloma cell lines and primary patient cells has been demonstrated in preclinical studies. In the first-in-human phase 1 study (DREAMM-1/BMA117159, NCT02064387), belantamab mafodotin had a manageable safety profile and demonstrated a rapid, deep, and durable clinical response as a monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). In a cohort of 35 heavily pretreated patients with RRMM (57% with ≥5 lines of prior therapy) who received belantamab mafodotin 3.4 mg/kg by intravenous (IV) infusion every 3 weeks (Q3W) overall response rate (ORR) of 60% (95% confidence interval [CI]: 42.1, 76.1) was demonstrated. The median progression-free survival (PFS) was 12.0 months (95% CI: 3.1, not estimable [NE]) and the median duration of response (DoR) was 14.3 months (95% CI: 10.6, NE). Belantamab mafodotin monotherapy in patients with RRMM is being further evaluated against the standard-of-care pomalidomide/dexamethasone (Pom/Dex) regimen in the DREAMM-3 study. Methods: The phase 3, multicenter, randomized, open-label DREAMM-3 study will evaluate the efficacy and safety of belantamab mafodotin monotherapy compared with Pom/Dex, an established standard-of-care regimen in RRMM. In this global study, patients treated with ≥2 prior lines of therapy, including ≥2 consecutive cycles of both lenalidomide and a proteasome inhibitor, and refractory to the last line of treatment, will be eligible for inclusion. Participants with prior allogeneic transplant will be excluded, as will those with prior exposure to BCMA-targeted therapies and Pom. Approximately 320 participants will be randomized (2:1) to receive either belantamab mafodotin or Pom/Dex and will be stratified by age, exposure to anti-CD38 therapy, and number of prior lines of treatment. Belantamab mafodotin will be administered IV Q3W, at the dose confirmed in the ongoing DREAMM-2 study (NCT03525678). Pom will be administered orally at 4 mg on Days 1-21 of each 28-day cycle, with Dex 40 or 20 mg (depending on age) on Days 1, 8, 15, and 22. Treatment in both arms will continue until progressive disease, unacceptable toxicity, or death. The primary endpoint is PFS, and overall survival is a key secondary endpoint. Additional secondary endpoints include ORR, time to response, minimal residual disease negativity rate (10-5 threshold assessed by next-generation sequencing), DoR, safety, and health-related quality of life. Bone marrow and blood samples will be collected for biomarker research. The study is planned to start in late 2019. Acknowledgments: Editorial assistance was provided by Sarah Hauze, PhD, at Fishawack Indicia Ltd, UK, and funded by GlaxoSmithKline. Study is funded by GlaxoSmithKline (ID: 207495); drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa. Disclosures Weisel: Sanofi: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria; GSK: Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Juno: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Hopkins:GSK: Employment, Equity Ownership. Fecteau:GSK: Employment, Equity Ownership. Bao:GSK: Employment, Equity Ownership. Quigley:GSK: Employment, Equity Ownership. Jewell:GSK: Employment, Equity Ownership. Nichols:GSK: Employment, Equity Ownership. Opalinska:GSK: Employment, Equity Ownership.

A Phase 1, Dose-Escalation Study (CHAMPION-1) Investigating Weekly Carfilzomib In Combination With Dexamethasone For Patients With Relapsed Or Refractory Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1934-1934 ◽  
Author(s):  
James R. Berenson ◽  
Leonard Klein ◽  
Robert M. Rifkin ◽  
Priti Patel ◽  
Sandra Dixon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Single Agent ◽  
Employment Equity ◽  
Advisory Committees ◽  
Refractory Multiple Myeloma ◽  
The Us ◽  
Equity Ownership

Abstract Introduction Carfilzomib (CFZ) is a selective proteasome inhibitor approved in the US for the treatment of relapsed and refractory multiple myeloma (MM) (Kyprolis PI, 2012). The approved dose and schedule for single-agent CFZ is 20/27 mg/m2 administered intravenously (IV) over 2–10 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Using the same consecutive daily dosing schedule, 56 mg/m2 CFZ administered IV over 30 minutes has been found to be well tolerated as a single agent or in combination with dexamethasone (DEX), with an overall response rate (ORR) of 55%–60% for patients (pts) with relapsed and refractory MM (Badros et al, ASH 2012, abstract 4036). In this multicenter single-arm phase 1/2 study (CHAMPION-1; NCT01677858), we are evaluating the safety and efficacy of once-weekly CFZ with DEX. Results from the phase 1 dose-escalation portion of the study are presented herein, including an evaluation of safety, pharmacokinetics (PKs), clinical benefit rate (CBR, ≥minimal response [MR]), ORR (≥partial response [PR]), and time to response. Methods Pts with relapsed or refractory MM who had received 1−3 prior regimens were eligible for enrollment. Pts were treated with CFZ as a 30-minute IV infusion on days 1, 8, and 15 of each 28-day cycle in a standard 3+3 dose-escalation scheme. All pts received CFZ (20 mg/m2) on day 1 of cycle 1; subsequent doses started at 45 mg/m2 in the first cohort and were escalated to 56, 70, or 88 mg/m2in successive cohorts until the maximum tolerated dose (MTD) was determined. Pts also received 40 mg DEX (IV or oral administration) on days 1, 8, 15, and 22 of cycles 1–8. During cycle 9 and beyond, patients continued to receive the same doses and schedules of CFZ and DEX, with the exception that DEX was not administered on day 22. The primary objective of the phase 1 portion of the study was to determine the MTD of weekly CFZ plus DEX. Response was assessed by IMWG criteria. MR was assessed by EBMT criteria. Results As of July 11, 2013, 18 pts have been enrolled, with a median age of 63 years (range, 43–84), and a median of 1 prior regimen (range, 1–2). The 45 and 56 mg/m2 dosing cohorts enrolled 3 pts each, and the 70 and 88 mg/m2 dosing cohorts enrolled 6 pts each. Pts have received a median of 5.5 cycles of treatment. At 88 mg/m2, 2 dose-limiting toxicities (DLTs) were observed: grade [Gr] 3 dyspnea and Gr 3 vomiting. All 18 pts were evaluable for safety. The only grade 3 adverse event (AE) reported in more than 1 patient was increased blood creatinine (n=2). Four serious AEs were reported in 3 pts: Gr 3 dyspnea, Gr 3 pneumonia, Gr 3 increased blood creatinine, and Gr 4 hyponatremia. No peripheral neuropathy was reported. Six pts discontinued treatment for the following reasons: AEs of decreased renal function (n=1) and dyspnea (n=1), progressive disease (n=2), physician decision (n=1), and withdrawal of consent (n=1). Five patients had a dose reduction from 88 mg/m2 to 70 mg/m2 (1 due to an AE, 1 due to a DLT, and 3 per protocol due to the 2 DLTs in the 88 mg/kg2 cohort); 2 of the 5 pts had an additional dose reduction owing to AEs. PK analysis (n=12) from pts that received 20, 70, or 88 mg/m2 of CFZ showed a dose-dependent increase in mean Cmax (703, 2640, and 3172 ng/mL, respectively) and AUC (283, 1045, and 1247 h·ng/mL, respectively) for CFZ. The mean terminal half-life was ∼0.8 h. Fifteen pts were included in the response evaluation; 3 pts did not have a postbaseline assessment at the time of the data cutoff. The ORR was 67%, and the CBR was 87% (4 pts achieved a complete response, 1 very good PR, 5 PR, and 3 MR). One pt had stable disease, and 1 pt was not evaluable for response, as the pt had a DLT and was no longer on treatment. Median time to response for pts that achieved a ≥PR (n=10) was 1.6 months. Conclusions These preliminary results demonstrate that weekly CFZ at doses ≥45 mg/m2 in combination with DEX in pts with relapsed or refractory MM was tolerated and showed rapid and promising efficacy with an ORR of 67% and a CBR of 87%. Weekly infusion of 70 mg/m2 CFZ demonstrated a lower Cmax, comparable half-life, and higher AUC per cycle compared with the currently approved twice-weekly CFZ dosing regimen. Overall, these findings suggest that CFZ at doses up to 70 mg/m2 in combination with DEX may be administered in a convenient once-weekly schedule. The study is ongoing to confirm the MTD at 70 mg/m2, at which point the phase 2 portion of the study will be initiated. Disclosures: Berenson: Onyx: Consultancy, Honoraria, Research Funding. Off Label Use: Carfilzomib is a selective proteasome inhibitor that is approved in the US for the treatment of relapsed and refractory multiple myeloma. Klein:USONC: Employment. Rifkin:Onyx: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: The Takeda Oncology Company: Membership on an entity’s Board of Directors or advisory committees. Patel:Onyx: Employment, Equity Ownership. Dixon:Onyx: Employment, Equity Ownership. Ou:Onyx: Employment, Equity Ownership.

scholarly journals Current Real-World Treatment Patterns and Outcomes in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3290-3290
Author(s):  
Jenny Willson ◽  
Amanda Bruno ◽  
Joanna Opalinska ◽  
Jeannene Nelson ◽  
Orsolya Lunacsek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Real World ◽  
Bone Pain ◽  
Chart Review ◽  
Treatment Patterns ◽  
Employment Equity ◽  
Refractory Multiple Myeloma ◽  
Equity Ownership ◽  
Line Of Therapy

Abstract Introduction: Limited real-world data exist on treatments for relapsed/refractory multiple myeloma (RRMM) since the approval of several new agents. This study assessed treatment patterns and outcomes of patients with RRMM receiving ≥2 lines of therapy in US community oncology practices. Methods: A chart review was conducted in patients ≥18 years with MM diagnosed January 1, 2011-May 31, 2017, from a large electronic medical record database. Patient data were examined from the date of initiation of first-line therapy (1LT) for MM until death, loss to follow-up, or study end date, whichever was earliest. This study was hypothesis generating, thus no statistical tests were performed. Descriptive statistics were used to describe baseline demographic/clinical characteristics, treatment patterns, median progression-free survival (mPFS) and median overall survival (mOS) for the overall RRMM population. Patients were then stratified into "older" vs. "newer" treatment cohorts based on whether the drugs used in each line of therapy were approved before, or after 2013. Results: Of 1005 charts reviewed, 456 patients had received ≥2 lines of therapy and were included in the chart review study (median age at diagnosis: 70.4 years; females: 39.5%, males 60.5%; bone involvement at diagnosis: 66.0%; International Staging System stage within 1 month of diagnosis: I 28.7%, II 27.9%, III 43.4%; 183 (40.1%) patients received 3LT, 75 (16.4%) 4LT, and 29 (6.4%) 5LT. 1LT was dominated by bortezomib (BTZ), lenalidomide (LEN), and the combination of the two, with 93.3% of patients using these agents as 1LT and 69.8% of patients as 2LT. In 3LT and beyond, there was greater use of newly approved drugs (approved since 2013) compared with 1LT and 2LT; pomalidomide (14.8% 3LT, 17.3% 4LT, 17.2% 5LT), carfilzomib (19.1% 3LT, 13.3% 4LT, 17.2% 5LT), elotuzumab (2.2% 3LT, 4.0% 4LT, 3.4% 5LT), panobinostat (0% 3LT, 2.7% 4LT, 3.4% 5LT), daratumumab (6.6% 3LT, 13.3% 4LT, 17.2% 5LT), and ixazomib (0% 3LT, 1.3% 4LT, 3.4% 5LT) with the exception of the BTZ/LEN combination. However, patients receiving either BTZ, LEN, or both in combination as 1LT or 2LT often received the agent(s) as re-treatment in lines 2-6 (46.2%-55.6%). Median time on treatment decreased from 7.5 months in 1LT to ≤2.3 months in 4LT and 5LT, and median treatment-free intervals decreased from 1.6 months between 1LT and 2LT to 0.5 months between 4LT and 5LT. The most common reason for discontinuation was disease progression and drug toxicity/intolerability. The most commonly reported adverse events (AEs) for all lines of therapy were fatigue (71.6%-78.3%), bone pain (38.5%-69.1%) and anemia (53.8%-69.3%). AEs were generally constant across lines of therapy, except for bone pain, anemia, and neuropathy, which broadly decreased with increasing line of therapy. Overall, mPFS ranged from 12.0 months in 1LT to 3.5 months in 5LT and mOS ranged from 48.2 months in 1LT to 5.8 months in 5LT (Figure 1). A trend for increased mPFS and mOS with newer vs. older drugs was observed across treatment lines. The magnitude of the "new" treatment benefit on mPFS was pronounced in 1LT. Conclusions: Forty percent of patients received therapy beyond 2lines demonstrating a great unmet need in the treatment of RRMM. While BTZ and LEN were predominant in 1st and 2nd lines, substantial fragmentation was seen in ≥3 line, highlighting the lack of defined treatment pathways for these patients. The results further indicated that treatments beyond 2LT offer shorter benefit as disease progresses; median time on treatment and mPFS decreased as treatment line increased. Also, median PFS and OS in this real-world analysis were also slightly lower than that observed in recent clinical trials of novel agents, which is consistent with other real-world studies. While there remains a need to replicate these results within a larger dataset where statistical comparisons could be made and confounding factors controlled for, the trends observed in this study suggest improved PFS and OS outcomes may be associated with newly approved treatments. In particular, the trends suggested that newer treatments may have a greater mPFS benefit vs. older treatments if used in earlier lines of treatment. Funding: GSK (HO-17-17767) Disclosures Willson: GlaxoSmithKline: Employment, Equity Ownership. Bruno:GlaxoSmithKline: Employment, Equity Ownership. Opalinska:GlaxoSmithKline: Employment, Equity Ownership. Nelson:GlaxoSmithKline: Equity Ownership. Stafkey-Mailey:Xcenda: Employment.

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