Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany

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.

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

10.21203/rs.3.rs-45379/v3 ◽

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.

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

10.21203/rs.3.rs-45379/v1 ◽

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.

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

Future Oncology ◽

10.2217/fon-2020-1225 ◽

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)

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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 ◽

10.1186/s12885-020-07732-1 ◽

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.

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

10.21203/rs.3.rs-45379/v2 ◽

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.

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