scholarly journals Survival Benefit of Ixazomib, Lenalidomide and Dexamethasone (IRD) over Lenalidomide and Dexamethasone (Rd) in Relapsed and Refractory Multiple Myeloma Patients in Routine Clinical Practice

2020 ◽  
Author(s):  
Jiri Minarik ◽  
Tomas Pika ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
Jan Straub ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Response Rate ◽  
Statistical Tests ◽  
Cox Proportional Hazards ◽  
Routine Clinical Practice ◽  
Refractory Multiple Myeloma ◽  
Survival Endpoints

Abstract Background: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods: A total of 344 patients treated with IRD (N=127) or RD (N=217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05.Results: In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51 – 0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0 % in the IRD group vs 66.2 % in the RD group with a complete response rate (CR) of 11.1 % vs 8.8 %, and very good partial response (VGPR) 22.2 % vs 13.9 %, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

scholarly journals Survival Benefit of Ixazomib, Lenalidomide and Dexamethasone (IRD) over Lenalidomide and Dexamethasone (Rd) in Relapsed and Refractory Multiple Myeloma Patients in Routine Clinical Practice

2021 ◽  
Author(s):  
Jiri Minarik ◽  
Tomas Pika ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
Jan Straub ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Response Rate ◽  
Statistical Tests ◽  
Cox Proportional Hazards ◽  
Routine Clinical Practice ◽  
Refractory Multiple Myeloma ◽  
Survival Endpoints

Abstract Background: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods: A total of 344 patients treated with IRD (N=127) or RD (N=217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05.Results: In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51 – 0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0 % in the IRD group vs 66.2 % in the RD group with a complete response rate (CR) of 11.1 % vs 8.8 %, and very good partial response (VGPR) 22.2 % vs 13.9 %, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

scholarly journals Survival Benefit of Ixazomib, Lenalidomide and Dexamethasone (IRD) Over Lenalidomide and Dexamethasone (Rd) in Relapsed and Refractory Multiple Myeloma Patients in Routine Clinical Practice

2020 ◽  
Author(s):  
Jiri Minarik ◽  
Tomas Pika ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
Jan Straub ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Response Rate ◽  
Statistical Tests ◽  
Cox Proportional Hazards ◽  
Routine Clinical Practice ◽  
Refractory Multiple Myeloma ◽  
Survival Endpoints

Abstract Background: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods: A total of 344 patients treated with IRD (N=127) or RD (N=217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable Cox proportional hazards models were used to evaluate the effect of treatment regimen. Statistical tests were performed at significance level 0.05.Results: In the whole cohort, PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51 – 0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0 % in the IRD group vs 66.2 % in the RD group with a complete response rate (CR) of 11.1 % vs 8.8 %, and very good partial response (VGPR) 22.2 % vs 13.9 %, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

scholarly journals Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiri Minarik ◽  
Tomas Pika ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
Jan Straub ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Response Rate ◽  
Statistical Tests ◽  
Cox Proportional Hazards ◽  
Routine Clinical Practice ◽  
Refractory Multiple Myeloma ◽  
Survival Endpoints

Abstract Background We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. Methods A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient’s characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05. Results In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1–3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51–0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Conclusions Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

Relationship of Carfilzomib Dosing and Duration of Therapy (DOT) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4235-4235
Author(s):  
R. Donald Harvey ◽  
Yaozhu J. Chen ◽  
Jan Lethen ◽  
Maya Mahue
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Dose Escalation ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Standard Dose ◽  
Cox Proportional Hazards ◽  
Refractory Multiple Myeloma ◽  
Duration Of Therapy

Abstract Background Carfilzomib (CFZ), an epoxyketone proteasome inhibitor, was approved in July 2012 for the treatment of patients with relapsed and refractory multiple myeloma (RRMM) in the US. The approved dosing schedule then (before a new label released in July 2015) was an intravenous infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. The starting dose is 20 mg/m2/day during Cycle 1; if well tolerated, it should be escalated to a target dose of 27 mg/m2/day in Cycles 2+. There exists evidence in oncology studies that reductions from standard dose and dose-intensity may compromise health outcomes (Lyman GH 2009); however, literature based on real-world CFZ dosing data is sparse. The objective of this study was to retrospectively assess the association between CFZ dose escalation in routine clinical practice and duration of therapy (DOT). Methods Data were obtained from a large US-based electronic medical record database, which comprises about 20% of US cancer patients who are geographically and demographically diverse. Adult multiple myeloma (MM) patients were included if they were: receiving CFZ between July 20, 2012 and April 30, 2015 after previous exposure to bortezomib and an immunomodulatory agent; no CFZ use before MM diagnosis; >1 cycle of CFZ use. To adjust for clinical practice variations, 10% variability was allowed for the recommended dose levels of 20 mg/m2 and 27 mg/m2. Patients with all their Cycle 1 doses within 10% of 20 mg/m2 were included in an analysis of dose escalation. Patients were classified as "early escalators" if their dose increased to 27 mg/m2 on day 29 (start of Cycle 2), or as "late escalators" if the dose increased to 27 mg/m2 after day 29, or as "non-escalators" if their dose never increased to 27 mg/m2 during the follow-up. DOT was calculated from CFZ initiation date to the last day of that CFZ regimen (ended by treatment discontinuation, death or loss to follow up, whichever comes first). The effect of dosing escalation ("early escalators" vs. "late escalator" vs. "non-escalator") with regard to DOT was assessed using Kaplan-Meier method; statistical significance of differences in DOT across three groups was evaluated with Cox proportional hazards regression model, controlling for patient's baseline demographic and clinical characteristics and also occurrence of events (e.g., renal complications, cardiac events, hematologic comorbidities) in Cycle 1. Results A total of 435 CFZ users meeting selection criteria were retrospectively identified, 54% male, with a median (interquartile range [IQR]) age of 69 (61-76) years and 65% (n=283) aged 65+; 70% were White, 16% Black, 2% Asian and 12% Other. More than half (57%, n=248) lived in the South, 18% in the Northeast, 13% in the Midwest, and 12% in the West. In the 1-year before CFZ start, 40% of the patients had chronic kidney disease, 18% had kidney failure, and 2% had a cardiac condition; at CFZ initiation, 14%, 31%, 8% and 2% of patients had ECOG performance status of 0, 1, 2, 3, respectively. During the course of CFZ treatment (i.e., DOT, median 112 days, IQR 70-196 days), 15% had a concomitant use of granulocyte-colony stimulating factor (G-CSF); 49% (n=215) escalated to ≥27 mg/m2 at the start of Cycle 2, 33% (n=142) escalated later than Cycle 2 start, and the remaining 18% (n=78) did not escalate. Among the two escalator groups, median (IQR) time to first escalation was 28 (28-28) days for "early escalator" and 35 (30-42) days for "late escalator"; both were within Cycle 2 (days 29-56) as standard dose escalation. Median DOTs were 161 days for "early escalator", 139 days for "late escalator" and 98 days for "non-escalator", p=0.0041 (Figure 1). Multivariate Cox proportional hazards modeling showed that early and late escalators had 34% (hazard ratio [HR]=0.66, p=0.002) and 38% (HR=0.62, p=0.001) lower risks of CFZ discontinuation relative to non-escalators, respectively. In addition, with (vs. without) concomitant G-CSF use suggested a 25% (HR=0.75, p=0.047) lower risk to discontinue CFZ. Conclusions The data from this study indicate that CFZ administration in standard dose escalation is associated with lower risk of treatment discontinuation for RRMM patients. Further investigation of the time-varying effect of dose escalation as well as treatment-induced adverse events is needed to understand the impact of various factors on physician's decisions in clinical practice to continue or discontinue multiple myeloma treatment. Disclosures Harvey: Onyx/Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Chen:Onyx Pharmaceuticals: Employment. Lethen:Amgen: Employment. Mahue:Amgen - Onyx Pharmaceuticals: Employment.

Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients.

1993 ◽  
Vol 11 (6) ◽  
pp. 1165-1171 ◽  
Author(s):  
J Bladé ◽  
J F San Miguel ◽  
A Alcalá ◽  
J Maldonado ◽  
M A Sanz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Combination Chemotherapy ◽  
Proportional Hazards ◽  
Response Rate ◽  
Objective Response ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Multicentric Study ◽  
Cox Proportional Hazards Models

PURPOSE To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005). CONCLUSION These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.

scholarly journals Four-Year Interim Analysis of Miroir, a French Multicenter, Non-Interventional Study of Pomalidomide in Relapsed/Refractory Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1836-1836
Author(s):  
Olivier Decaux ◽  
Margaret Macro ◽  
Sophie Gourgou ◽  
Florence Lachenal ◽  
Caroline Bureau Lenoir ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Board Of Directors ◽  
Interim Analysis ◽  
Research Funding ◽  
Routine Clinical Practice ◽  
Interventional Study ◽  
Real World Data ◽  
Advisory Committees ◽  
Refractory Multiple Myeloma

BACKGROUND Real-world data on the use of pomalidomide (POM) for the treatment (Tx) of relapsed/refractory multiple myeloma (RRMM) are limited. The MIROIR study was designed to evaluate POM Tx in routine clinical practice in France. Here, we present results from a prespecified 4-year interim analysis. METHODS MIROIR is a multicenter, observational, ambispective, non-interventional study of POM in routine clinical practice. Adult patients (pts) with MM who initiated POM Tx in France between October 1, 2014, and September 30, 2018, were included. All pts were required to be enrolled in the French IMNOVID® registry. Data were collected from medical records of consenting pts. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. The primary endpoint is progression-free survival (PFS) at 6 months. Key secondary endpoints include time to next Tx (TTNT), overall survival (OS), and safety. This study is ongoing; targeted enrollment is 3000 pts (ClinicalTrials.gov, NCT02902900). RESULTS A total of 2099 pts were included in this analysis (median follow-up: 23.3 months; data cutoff: February 1, 2019). Median age was 70.0 years, and 655 pts (31.2%) were aged ≥ 75 years; 1134 pts (54.0%) were male. Median time from start of first-line Tx to POM initiation was 51.4 months. Pts had received a median of 3 prior lines of therapy (range: 0-9), with 914 (43.5%), 644 (30.7%), 312 (14.9%) and 229 pts (10.9%) receiving ≤ 2, 3, 4, and ≥ 5 prior lines, respectively. From 2014 to 2016, the median number of prior lines of therapy before POM initiation was 3, and from 2016 to 2018, the median was 2. Nearly all pts received prior lenalidomide (LEN; 97.0%) and bortezomib (96.7%). POM was initiated at 4 mg/day in 1635 pts (77.9%) overall and in 1216 pts (84.2%) aged < 75 years and in 419 pts (64.0%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 507 (35.1%) and 732 pts (50.7%) aged < 75 years and in 405 (61.8%) and 62 pts (9.5%) aged ≥ 75 years. Overall, the 6-month PFS rate was 51.7% (95% CI, 49.4%-54.1%). Other key PFS data in pt subgroups are reported in the Table. In the overall population, median TTNT, 12-month OS rate, and median OS were 10.4 months (95% CI, 9.7-11.2), 70.6% (95% CI, 68.5-72.6), and 24.6 months (95% CI, 22.9-not reached), respectively. Among 1164 pts (55.5%) with ≥ 1 adverse event (AE), the most common AEs were neutropenia (290 pts; 24.9%), infections (263 pts; 22.6%), thrombocytopenia (99 pts; 8.5%), and asthenia (87 pts; 7.5%). POM dose was reduced due to an AE in 20.7% of pts; POM Tx was interrupted or discontinued due to an AE in 36.2% and 15.2% of pts, respectively. CONCLUSIONS The results of this interim analysis confirm the efficacy of POM reported in clinical trials and underscore its role in Tx of RRMM, including after LEN Tx. Median PFS in pts with ≤ 2 prior Tx lines was numerically longer than in pts who had more Tx lines, supporting earlier Tx with POM. PFS outcomes were similar regardless of the duration of LEN Tx (< or ≥ 6 months) before initiation of POM and whether pts had received LEN or another Tx as their most recent therapy. The latter finding suggests that POM can be used after relapse or resistance to LEN and that there is no need to replace an IMiD agent with another class of treatment. Disclosures Decaux: Celgene Corporation, Janssen, Takeda, Amgen: Honoraria. Macro:Celgene, Janssen, Amgen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support. Gourgou:Celgene: Employment, Equity Ownership. Lachenal:Celgene: Other: Scientific Comittee's. Stoppa:Celgene: Honoraria. Jaccard:Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Karlin:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; 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, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fohrer:Celgene: Consultancy, Honoraria. Leleu:Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria.

scholarly journals A phase 2, open-label, multicenter study of ixazomib plus lenalidomide and dexamethasone in adult Japanese patients with relapsed and/or refractory multiple myeloma

2021 ◽  
Author(s):  
Shinsuke Iida ◽  
Tohru Izumi ◽  
Takuya Komeno ◽  
Yasuhito Terui ◽  
Takaaki Chou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Confidence Interval ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Open Label ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Good Partial Response

Abstract Background TOURMALINE-MM1 was a global study that demonstrated a significant improvement in progression-free survival with ixazomib plus lenalidomide and dexamethasone compared with placebo plus lenalidomide and dexamethasone, in patients with relapsed and/or refractory multiple myeloma. The current study was conducted to evaluate further the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients. Methods This phase 2, open-label, single-arm, multicenter study enrolled patients aged ≥ 20 years with relapsed and/or refractory multiple myeloma at 16 sites in Japan. Patients refractory to lenalidomide or proteasome inhibitor-based therapy at any line were excluded. The primary endpoint was the rate of very good partial response or better in the response-evaluable analysis set. Secondary endpoints were progression-free survival, overall response rate, duration of response, time to progression, overall survival and safety. Results In total, 34 patients were enrolled. The rate of very good partial response or better was 50.0% (95% confidence interval 31.9–68.1) and the overall response rate was 84.4% (95% confidence interval 67.2–94.7). Median progression-free survival was 22.0 months (95% confidence interval 17.3–not evaluable) and median overall survival was not estimable. The safety profile of ixazomib plus lenalidomide and dexamethasone in this study was similar to that in the TOURMALINE-MM1 study. Conclusions The efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients with relapsed and/or refractory multiple myeloma are comparable with reported TOURMALINE-MM1 study results. Clinicaltrials.gov identifier NCT02917941; date of registration September 28, 2016.

scholarly journals Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma

2021 ◽  
Author(s):  
Roman Hájek ◽  
Jiří Minařík ◽  
Jan Straub ◽  
Luděk Pour ◽  
Alexandra Jungova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Progression Free Survival ◽  
Routine Clinical Practice ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Level Data ◽  
Dose Reductions

Aim: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed. Results: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events. Conclusion: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1. Clinical trial registration: NCT02761187 (ClinicalTrials.gov)

scholarly journals The challenge of managing severe delirium: an observational study of the effects of pharmacological and supportive care on delirium duration and resolution in 602 patients

2019 ◽  
Author(s):  
Carl Moritz Zipser ◽  
Peter Hayoz ◽  
Silvana Knöpfel ◽  
Peter Peyk ◽  
Maria Schubert ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Supportive Care ◽  
Proportional Hazards ◽  
Dual Therapy ◽  
Estimating Equation ◽  
Cox Proportional Hazards ◽  
Routine Clinical Practice ◽  
Hospitalised Patients ◽  
Observational Cohort ◽  
Management Approaches

Abstract Background: Delirium is the most common neuropsychiatric disorder seen in hospitalised patients. Current guidelines recommend only using antipsychotics with distressed patients. Nonetheless, in routine clinical practice, multiple psychotropics are commonly administered. More evidence on the short-term benefits of various management approaches in patients with delirium is required. Methods: In this observational cohort study, 602 delirious patients were followed for twenty days. Supportive care was provided to all patients in addition to either no psychotropic therapy, monotherapy, dual therapy, or polytherapy defined as three or more psychotropic drugs. The effectiveness of interventions regarding delirium resolution and symptom severity was determined by Cox proportional hazards regression and generalized estimating equation models. Results: Psychotropics were commonly used to manage delirium. In total, 12.1% of patients received polytherapy, 37.2% dual therapy, 37.7% monotherapy, and 12.1% supportive care alone (i.e., almost half of the patients received ≥ two psychotropics). Patients who received polytherapy had higher initial baseline delirium severity and exposed the mixed subtype more often; with the latter delirium lasted longer and recovery was less frequent than in mild delirium. Providing supportive care alone in mild delirium was superior to all psychotropic approaches. Conclusions: In routine clinical practice, the use of multiple psychotropics is common. In our study, however, despite combined supportive management and polypharmacy, patients with severe delirium suffer longer from delirium and have lower resolution rates. For the management of patients with mild delirium supportive care alone can be considered. When psychotropics are considered, single psychotropics and dose optimisation are recommended. These findings underline the challenge of managing severe delirium.

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