Characterization of Patients with Multiple Myeloma Achieving Complete Response to Bortezomib: An Interim Report From An International Electronic Observational Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4938-4938
Author(s):  
Michel Delforge ◽  
Hadewijch De Samblanx ◽  
Maria Roussou ◽  
Konstantinos Zervas ◽  
Eirini Katodritou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Clinical Practice ◽  
Observational Study ◽  
Complete Response ◽  
Practice Setting ◽  
Employment Equity ◽  
Clinical Practice Setting ◽  
Equity Ownership ◽  
Response Groups

Abstract Abstract 4938 Introduction Bortezomib (Velcade®) is effective and well tolerated in patients with multiple myeloma (MM), including those with adverse prognostic factors such as advanced age, more prior lines of therapy, and advanced-stage disease. The international, non-interventional, Electronic Velcade Observational Study (eVOBS) is an ongoing observational study that aims to assess the clinical and health economic outcomes in MM patients treated with bortezomib in the clinical-practice setting. In this study, we characterized patients achieving complete response (CR) with bortezomib in the relapsed/refractory setting, and assessed the effects of adverse prognostic factors on the rate of CR. Methods Adult patients from Belgium, France, Greece, Russia, Spain, Sweden, and Turkey scheduled to receive bortezomib for relapsed MM were eligible for inclusion in eVOBS. All bortezomib doses and concomitant treatments (except investigational therapies) were permitted; dose adjustments and cycle delays were documented. Patients are being followed for up to 3 years to document long-term outcomes; data are collected at baseline and at the end of every bortezomib cycle. Due to the non-interventional nature of the study, no predefined response criteria were mandated; response criteria were defined by the investigator and may have included European Group for Blood and Marrow Transplantation (EBMT), Southwest Oncology Group (SWOG), or M-protein criteria. Patients who had at least 12 weeks data or who had died by the time of data cut-off (June 30, 2009) were included in this exploratory analysis; patients were assessed after completion of four and six cycles. Results A total of 769 patients were included, 129 (16.8%) of whom achieved CR. There were no significant differences in baseline characteristics between patients who did (n=129) vs did not (n=640) achieve CR: 49.8% vs 47.3% were male, median age at baseline was 60.6 vs 62.1 years, median age at diagnosis was 57.9 vs 59.4 years, and median time since diagnosis was 2.3 vs 2.4 years. Patients with adverse prognostic factors were evenly distributed among response groups: of the patients who achieved CR, 7.8%, 55.8%, 23.3%, and 13.2% had 0, 1, 2, and 3 or more prior lines of therapy, vs 3.6%, 56.1%, 23.4%, and 15.8% of those who did not achieve CR. Similar results were seen for patients across disease stages: 14.7%, 31.0%, and 46.5% of CR patients vs 12.3%, 33.1%, and 50.2% of non-CR patients had ISS disease stage I, II, or III, respectively. Similarly, patients with comorbidities such as obesity or diabetes were evenly distributed across response groups: 6.1% and 7.1% of CR patients had obesity or diabetes, respectively, vs 4.4% and 9.6% of non-CR patients. After 4 cycles, the overall response rate (ORR) in patients who had completed 4 cycles (n=518) was 70%, including 12% complete response (CR), 16% near-CR (nCR), and 42% partial response (PR). Improved response rates were seen with prolonged therapy; after 6 cycles, the ORR in patients who had completed 6 cycles (n=321) was 82%, including 16% CR, 20% nCR, and 46% PR. As shown in the Figure, analysis of overall survival by best response at cycle 4 showed that achieving a CR/nCR is associated with significantly improved survival versus PR (p<0.0001). Conclusions Together, these results show that bortezomib, as administered in the clinical-practice setting, is highly active in relapsed/refractory MM patients, with CRs achieved among all patient subgroups. Furthermore, achievement of CR appears associated with prolonged survival and responses to bortezomib appear to improve with prolonged duration of therapy. Disclosures Delforge: Celgene: Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria. Hulin:Janssen-Cilag: Honoraria; Celgene: Honoraria. Ganguly:Johnson & Johnson: Employment, Equity Ownership. Diels:Johnson & Johnson: Employment, Equity Ownership. Dhawan:Johnson and Johnson Research Pharmaceuticals: Employment. Dimopoulos:Millennium Pharmaceuticals, Inc.: Honoraria; Ortho-Biotech: Consultancy, Honoraria.

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.

Follow-up of Real Life Treated Multiple Myeloma Patients: Response, Disease Progression and Overall Survival,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3937-3937
Author(s):  
Hareth Nahi ◽  
Johan Liwing ◽  
Katarina Uttervall ◽  
Johan Andreasson ◽  
Astrid Gruber ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Real Life ◽  
M Protein ◽  
Novel Agents ◽  
Response Distribution ◽  
Employment Equity ◽  
Study Population ◽  
Equity Ownership

Abstract Abstract 3937 Treatment results in clinical practice and in real life can be different from each other. Therefore, evaluating real life outcomes in Multiple Myeloma (MM) patients in order to understand treatment outcome in clinical practice is very important. All patients diagnosed with MM and treated between Jan 2000 and Jul 2010 at Karolinska University Hospital, Huddinge and Södersjukhuset were included. Furthermore, all diagnosed patients between Jan 2005 and Jul 2010 at Karlolinska University Hopital, Solna were included. At diagnosis data regarding age, gender, type of myeloma and skeleton destruction as well as Ca, Hb, β2-microglobelin, albumin and creatinine were collected. For each treatment line, drugs given and specific start and stop dates for each drug were collected. Serum and urine M-protein was collected at baseline and each time the measurement differed from the previous. Near complete response (nCR) was defined as an immeasurable M-protein in the blood and urine by standard electrophoresis but not always confirmed by immunofixation since it was not required in clinical practice. Partial response (PR) was defined as a 50% reduction in M-protein. No response (NR) was defined as less than 50% reduction of M-protein. Progress was considered when M-protein increased with ≥ 25%. Novel agents were defined as bortezomib, lenalidomide and thalidomide. In the total population n=674, 89 (13%) patients were excluded due to non treatment demanding disease or plasmacytoma without MM diagnosis setting the study population to n=585. The median follow up of the study population was 815 days. The median age in the study population was 68 years and 45% were women. High dose treatment (HDT) was given to 214 (37%) patients. The median age in the HDT population was 58 years and 34% were women. The median age in the non-HDT population was 75 years and 51% was women. The median number of given treatment lines was 2. The proportion of patients receiving more treatment lines were declining rapidly with the number of received lines of therapy. The response distribution for the entire population nCR/PR/NR was 27/41/32 in 1st line, 18/34/48 in 2nd line. In the HDT population the same response distribution was 50/38/12 in 1st line and 28/38/34 in 2nd line. In the non-HDT population the response distribution was 14/43/43 in 1st line and 12/33/55 in 2nd line. The depth of the responses was significantly dependent on the line of therapy. Responses were significantly better in the HDT population vs. the non-HDT population in the first two treatment lines. There seems to be a correlation between the responses in 1st and 2nd line in the entire population. Improving the responses in 2nd line compared to 1st line seems not very likely. Statistical analysis shows that the non-HDT patients receiving novel agents in 1st line had a significantly higher probability of achieving nCR, 25% vs 9%.The same statistical difference was seen in the HDT patients with nCR rates of 65% vs 47%. The median TTP/TTNT for the study population was 309/381 days in the 1st line and 182/210 in 2nd line. In the HDT population the TTP/TTNT was 538/639 days in 1st line and 199/257 in 2nd line. In the non-HDT population the TTP/TTNT was 244/295 days in 1st line and 177/193 in 2nd line. In the HDT population both the TTP and the TTNT in the 1st line were significantly better than in the non-HDT population with no difference in the 2nd line. There was a significant trend of increasing TTP/TTNT in 1st line depending on the increased depth of the response. Statistical analysis showed that the use of novel agents in 1st line predicted a longer TTP for the non-HDT population. Median OS was 4.3 years 95% CI [3.9;5.0] with 53% censored. HDT patients had a significant longer median OS 6.3 years 95% CI [5.4;8.5] than the non-HDT patients OS 3.0 years 95% CI [2.2;3.6]. The median OS for non-HDT patients with 1st line best response nCR was 4.9 years, PR 3.3 years and NR 1.5 years. Kaplan-Mayer analysis shows that use of novel agents in the 1st line predicted a longer OS, median 5.1 years vs. 4.1 years. Patients receiving 2nd and 3rd line treatment were declining rapidly. To get a good response in 1st line increases the likelihood of having a good response in 2nd line. Receiving an nCR in 1st line seems to be very important and this study confirms the prognostic impact of achieving at least nCR. The use of novel agents improves the outcome for patients in clinical practice. Disclosures: Liwing: Janssen-Cilag: Employment, Equity Ownership. Näsman:Janssen-CIlag: Consultancy. Aschan:Janssen-Cilag: Employment, Equity Ownership.

Romiplostim for the Treatment of Adults with Primary Immune Thrombocytopenia (ITP) in Routine Clinical Practice in France – Interim Results From a Large Observational Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4643-4643
Author(s):  
Philippe Quittet ◽  
Mohamed Hamidou ◽  
Bernard Bonnotte ◽  
Olivier Fain ◽  
Kerry Dillingham ◽  
...  
Keyword(s):  
Platelet Count ◽  
Clinical Practice ◽  
Observational Study ◽  
Clinical Utility ◽  
Employment Equity ◽  
Large Observational Study ◽  
Equity Ownership ◽  
Grade 3 ◽  
Observation Period

Abstract Abstract 4643 Background: The thrombopoietin-receptor agonist (TPOra) romiplostim is recommended for second-line treatment of adult ITP (Provan, Blood 2010). Romiplostim registration studies were conducted in selected patient (pt) populations and may not reflect clinical practice. Moreover, regional variations may exist in the clinical utility of romiplostim. A recent French study enrolled adult ITP pts failing previous treatments and receiving romiplostim on a compassionate use basis before commercial availability (Khellaf, Blood 2011). We report interim data from French pts enrolled in a large observational study of romiplostim use in clinical practice, with broader inclusion criteria. Methods: This ongoing study enrolls ITP pts ≥18 years old, who have received romiplostim in clinical practice. Pts participating in another study, who initiated romiplostim prior to commercial launch or received other TPOra or related products are excluded. Data recorded as per clinical practice is collected for up to 2 years following romiplostim initiation. Study outcomes include pt characteristics (at romiplostim initiation), romiplostim dose, adverse drug reactions (ADRs) and bleeds, summarized for pts meeting the eligibility criteria (Full Analysis Set; FAS). Amgen (Europe) GmbH funded the study and medical writing assistance. Results: As of February 2012, 86 (95%) of 91 pts enrolled in France were included in the FAS. Of these, 59% (51/86) remained on study, 31% (27/86) had completed the 2-year observation period and 9% (8/86) had withdrawn (death, 6 [7%]; lost to follow-up, 2 [2%]). At romiplostim initiation, median (Q1, Q3) age, weight and platelet count were 65.0 (48.0, 77.0) years, 74.00 (62.20, 84.00) kg and 18.0 (7.0, 31.0) × 109/L; 38% (33/86) of pts had been diagnosed with ITP for < 1 year (median [Q1, Q3] time from diagnosis, 3.04 [0.51, 13.04] years), 74% (64/86) had received ≥3 prior ITP therapies, 71% (61/86) had received prior rituximab, 30% (26/86) were splenectomised and 52% (45/86) female. Romiplostim was initiated at 1 and ≥3 μg/kg/week in 63% (54/86) and 24% (21/86) of pts; 36% (31/86) of pts stopped romiplostim before the end of the 2-year observation period, with requirement for alternative therapy (11 [13%]), haemostatic platelet count/no further treatment necessary (6 [7%]; last platelet count before romiplostim stopped, 68–616 × 109/L; 1 pt splenectomised, 4 had ITP disease duration of <1 year, all had received 3–5 prior therapies, 1 later received corticosteroids) and ADR (4 [5%]) the most commonly specified reasons. Median (Q1, Q3) romiplostim exposure was 55.1 (29.9, 100.3) weeks (maximum 106 weeks); median follow-up after romiplostim initiation was 20.40 (14.50, 24.10) months. Median (Q1, Q3) average weekly dose over the observation period was 2.6 (1.4, 4.2) μg/kg/week, and 3.02 [2.00, 5.00] and 2.00 [1.14, 3.02] μg/kg/week after 1 and 2 years of treatment (months 10–12 [n=48] and 22–24 [n=23], respectively). Median platelet counts rose rapidly during the first 4 weeks of treatment and remained >50 × 109/L thereafter (Figure). Grade ≥3 bleeds were rare and occurred at a lower rate after romiplostim initiation (Table). The most commonly reported ADRs were thrombocytosis, asthenia, myalgia and headache (9.7–3.2 events per 100 pt-years). Three pts reported a total of 6 serious ADRs: pulmonary embolism, 2 events; deep vein thrombosis, drug ineffective, myelofibrosis (initial disease diagnosis inconsistent with ITP, myelofibrosis more likely due to MDS), and thrombocytosis (platelets 477 × 109/L), 1 event each. No fatal ADRs were reported. Summary/conclusions: This study provides further insight into the clinical utility of romiplostim in France. At an interim analysis, pts tended to have less chronic disease than those enrolled in a previous observational study (Khellaf, Blood 2011). With lower doses than reported by Khellaf, and no new safety signals, pts achieved sustained increases in platelet counts and experienced a lower rate of grade ≥3 bleeds following romiplostim initiation. Disclosures: Dillingham: Amgen: Employment, Equity Ownership. Kreuzbauer:Amgen: Employment, Equity Ownership.

Matching-Adjusted Indirect Comparison of Relative Efficacies Is Feasible and Useful in the Multiple Myeloma Therapy Landscape: A Comparison of Pomalidomide Plus Low-Dose Dexamethasone Versus Daratumumab

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5946-5946
Author(s):  
Kejal Parikh ◽  
Irina Proskorovsky ◽  
Safiya Abouzaid ◽  
Stanimira Krotneva ◽  
Veronique Page ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Research Funding ◽  
Low Dose ◽  
Indirect Comparison ◽  
Patient Characteristics ◽  
Employment Equity ◽  
Clinical Benefits ◽  
Adjusted Indirect Comparison ◽  
Equity Ownership

Abstract INTRODUCTION: Several new agents and regimens are available for the treatment of relapsed refractory multiple myeloma (RRMM). Comparison of all these is not feasible, yet therapeutic selections need to be made for optimal patient care. Both the MM-002 (Richardson et al., 2014) and MM-003 (San Miguel et al., 2013) trials have demonstrated the clinical benefits of pomalidomide plus low-dose dexamethasone (POM+LoDEX) in improving survival outcomes for patients with RRMM who had received ≥2 prior lines of therapy. Daratumumab (DARA) monotherapy was approved in the US for the treatment of RRMM patients, based on the results of a single-arm trial (SIRIUS) (Lonial et al., 2016). To date, there are no head-to-head studies comparing POM+LoDEX with DARA. We performed an indirect comparison of the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between POM+LoDEX and DARA in RRMM patients with ≥2 (median of 5) prior lines of therapy. METHODS: Matching-adjusted indirect comparison (MAIC) (Ishak et al., 2015; Signorovitch et al., 2012) is a method used to conduct indirect comparisons between relative efficacies of treatments after adjusting for imbalances across trials where the study populations were roughly similar. To perform a MAIC, it is necessary that the selected studies are compatible. Both MM-002 and SIRIUS were phase II trials and included mainly patients from North America, while other geographic regions were more widely represented in the phase III MM-003 trial. Thus, the MAIC was conducted using individual patient data from the intention-to-treat (ITT) population of POM+LoDEX from MM-002 and published aggregate data on patient characteristics and outcomes for the ITT population of DARA from SIRIUS. A propensity-score logistic regression equation was used to re-weight the POM+LoDEX patients such that their aggregate characteristics matched exactly those in SIRIUS for all prognostic factors (i.e., full set) which were available in both studies. These factors included age, gender, race, disease duration, immunoglobulin heavy chain type, Eastern Cooperative Oncology Group (ECOG) performance status, plasmacytoma, creatinine clearance, number of prior therapy lines, prior stem cell transplantation, and refractoriness to bortezomib, lenalidomide, or both. The relative treatment effects were estimated with a weighted logistic regression model for ORR and weighted Cox regression models for PFS and OS. Sensitivity analyses were also conducted by matching on only important prognostic factors (i.e., reduced set), identified from multivariate regression analyses for each endpoint. RESULTS: MM-002 and SIRIUS were generally similar in design and had sufficient overlap in baseline characteristics to allow adjustment for potential confounding. Most prognostic factors were similar between the two arms. However, patients on POM+LoDEX had worse ECOG status, while more patients on DARA had a plasmacytoma and creatinine clearance <60 mL/min and were refractory to lenalidomide, bortezomib, or both. After re-weighting, the aggregate patient characteristics for patients receiving POM+LoDEX matched those reported for DARA. The results from the analyses adjusting for all available characteristics showed no statistically significant differences in ORR, PFS, or OS between the two treatments. Similar findings were obtained by adjusting for important prognostic factors only (Table 1). OS results should be interpreted with caution as subsequent treatments cannot be adjusted for in a MAIC analysis. CONCLUSIONS: This analysis suggests that POM+LoDEX and DARA have similar clinical benefits with respect to ORR, PFS, and OS in RRMM patients with ≥2 prior lines of therapy. Treatment choice may be made between these two based on factors other than efficacy alone. MAIC analysis may be helpful in therapeutic decisions where direct comparative trials are not available, however as with any non-randomized study potential for residual confounding may still exist. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership, Research Funding. Proskorovsky:Evidera: Employment, Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Krotneva:Evidera: Employment, Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Page:Evidera: Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Pelligra:Evidera: Employment, Other: As a salaried Evidera employee, I am not allowed to accept any remuneration or honoraria. Evidera received funding from Celgene.. Guo:Celgene: Consultancy. Mouro:Celgene: Employment, Equity Ownership. Ailawadhi:Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.

scholarly journals Carfilzomib-Lenalidomide-Dexamethasone Versus Bortezomib-Lenalidomide-Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Results from the Prospective, Longitudinal, Observational Commpass Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 799-799 ◽  
Author(s):  
Ola Landgren ◽  
David S Siegel ◽  
Daniel Auclair ◽  
Ajai Chari ◽  
Michael Boedigheimer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Complete Response ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Immunomodulatory Drug ◽  
Frontline Therapy

Abstract Introduction: Triplet regimens incorporating a proteasome inhibitor and immunomodulatory drug are standards of care for the treatment of patients with newly diagnosed multiple myeloma (NDMM). The combinations of carfilzomib-lenalidomide-dexamethasone (KRd) and bortezomib-lenalidomide-dexamethasone (VRd) are recommended regimens for the treatment of NDMM by the National Comprehensive Care Network. However, there are limited data directly comparing the relative effectiveness and tolerability of these two regimens in patients with NDMM. Here, we report prospective evaluation of efficacy and preliminary tolerability data for patients who received KRd or VRd as frontline therapy in the Multiple Myeloma Research Foundation (MMRF) Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass, NCT01454297) study. Methods: CoMMpass is a prospective observational study conducted since 2011 by the MMRF that has enrolled over 1100 patients from Multiple Myeloma Research Consortium sites. Eligible adults with NDMM and symptomatic disease were enrolled within 30 days of initiating frontline therapy. Frontline therapy was chosen at the discretion of the investigator but must have included a proteasome inhibitor and/or immunomodulatory drug. In the current analysis, we evaluated the effectiveness and reasons for treatment discontinuation among enrolled patients who received KRd or VRd as first-line therapy. KRd patients were matched to VRd patients based on propensity score matching including age, gender, ISS and renal insufficiency as covariates. Treatment response was assessed by investigators and defined by International Myeloma Working Group Uniform Response Criteria. Event-free survival (EFS) was the pre-specified primary endpoint and defined as the time from the start of treatment until disease progression, death, or the initiation of new therapy. EFS was compared between treatment groups using a Cox proportional hazards model. Results: A total of 609 evaluable patients received first-line KRd (n=149) or VRd (n=460). Of these, 149 KRd patients and 149 VRd patients were matched according to baseline co-variates. Patient demographics and disease characteristics were balanced between treatment arms for the matched set of patients (KRd vs VRd) including by median age (years, 58 vs 59), gender (male, 63% vs 62%), and ISS (stage I, 46% vs 53%; stage II, 41% vs 40%; stage III, 13% vs 7%). With median follow up of 11.5 months for KRd and 41.9 months for VRd, 12-month EFS rates (95% CI) were 95% (90-99%) for KRd vs 84% (78-90%) for VRd (12-month HR, 0.28; 95% CI, 0.10-0.75; p=0.0043; Figure 1). By 12 months, 87% (95% CI, 81-93%) of KRd patients vs 68% (95% CI, 60-76%) of VRd patients had a partial response or better (p=0.0029) and 35% (95% CI, 25-45%) of KRd patients vs 14% (95% CI, 8-20%) of VRd patients achieved a complete response or better (p=0.0054; Figure 2). The treatment discontinuation rate due to adverse events was 3.4% for each arm. Conclusions: In the CoMMpass study, KRd demonstrated significant improvements in 12-month EFS compared with VRd in patients with NDMM (HR, 0.28; 95% CI, 0.10-0.75; p=0.0043). By 12 months, patients treated with KRd also achieved significantly higher response rates and complete response rates or better compared with VRd treated patients. Discontinuation rates due to AEs were similar between KRd and VRd. With limitations of non-randomized evaluation and relatively short median follow-up in the KRd arm, these results are consistent with previous single arm studies that KRd is not only effective but potentially a superior treatment option compared with VRd for patients with NDMM. Updated results with extended follow-up will be presented. Disclosures Landgren: Karyopharm: Consultancy; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Siegel:Novartis: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Speakers Bureau. Chari:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array Biopharma: Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Bristol Myers Squibb: Consultancy. Boedigheimer:Amgen Inc.: Employment, Equity Ownership. Welliver:Amgen: Employment, Equity Ownership. Mezzi:Amgen: Employment, Equity Ownership. Iskander:Amgen: Employment, Equity Ownership. Jakubowiak:Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; SkylineDx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals Renal impairment and use of nephrotoxic agents in patients with multiple myeloma in the clinical practice setting in the United States

2017 ◽  
Vol 6 (7) ◽  
pp. 1523-1530 ◽  
Author(s):  
Yi Qian ◽  
Debajyoti Bhowmik ◽  
Christopher Bond ◽  
Steven Wang ◽  
Sam Colman ◽  
...  
Keyword(s):  
United States ◽  
Multiple Myeloma ◽  
Clinical Practice ◽  
Renal Impairment ◽  
The United States ◽  
Practice Setting ◽  
Clinical Practice Setting
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