IXAZOMIB PLUS LENALIDOMIDE-DEXAMETHASONE (IRD) VS PLACEBO-RD IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): CHINA CONTINUATION OF TOURMALINE-MM1
(Abstract release date: 05/19/16)
EHA Library. Hou J. 06/09/16; 132854; E1305
Dr. Jian Hou
Contributions
Contributions
Abstract
Abstract: E1305
Type: Eposter Presentation
Background
The global, randomized, double-blind, placebo-controlled, phase 3 TOURMALINE-MM1 study (NCT01564537) demonstrated 35% improvement in PFS (HR 0.74, p=0.012) with IRd vs placebo-Rd in pts with RRMM (Moreau et al, ASH 2015).
Aims
This continuation study assessed the efficacy and safety of IRd vs placebo-Rd in pts with RRMM in China as a separate regional expansion of the global study.
Methods
Eligibility criteria and study design were per the global study, except high-risk cytogenetic and patient-reported outcome endpoints were not assessed. The primary endpoint was PFS, assessed by the same independent review committee (IRC) used in the global study. Pts were analyzed separately from the global study. Sample size was not based on a formal statistical hypothesis.
Results
115 pts were randomized and treated (57 IRd, 58 placebo-Rd). Compared to the global study, pts had more advanced disease (63% ISS stage II/III vs 46% in the global study), were more heavily pretreated (60% vs 41% had 2 or 3 prior therapies), had more frequently received prior thalidomide (84% vs 45%), and more frequently had refractory MM (43% vs 11%). At data cut-off (12 July 2015; median follow-up 8.0 vs 7.8 mos for IRd vs placebo-Rd), PFS was significantly improved with IRd vs placebo-Rd: median PFS 6.7 vs 4.0 mos; HR 0.598; 95% CI 0.367–0.972; p=0.035. This benefit was seen across most prespecified subgroups including those with ISS stage I/II at screening, pts who had received 2–3 prior therapies, or prior proteasome inhibitor/IMiD compound therapy. A prespecified sensitivity analysis of PFS according to the EMA censoring rules was consistent with the primary analysis: median PFS 5.8 mos vs 4.0 mos; HR 0.543; 95% CI, 0.340–0.869; p=0.009. TTP was also significantly improved with IRd vs placebo-Rd: median TTP 7.3 vs 4.1 mos; HR=0.583; p=0.032. OS data were not yet mature; 6 (11%) IRd and 16 (28%) placebo-Rd pts have died. The study remains blinded and is ongoing with a final analysis for mature OS data planned. Overall response rate was 56% vs 31% (odds ratio=2.84, p=0.007); the ≥VGPR rate was 25% vs 12%. Among responders, the median duration of response was 7.4 mos with IRd vs 5.6 mos with placebo-Rd. Pts had received a median of 7 and 5 cycles of IRd and placebo-Rd, and 59% and 41% of pts remained on treatment. The median relative dose intensities of all drugs were high (>95%), similar between arms, and consistent with the global study. The overall safety profile was similar in both treatment groups: 56% vs 62% had grade ≥3 AEs, 23% vs 26% had SAEs, 5% vs 12% discontinued treatment due to AEs, and 4% vs 5% died on treatment. Common grade ≥3 AEs with IRd vs placebo-Rd included thrombocytopenia (23% vs 13%), neutropenia (23% vs 19%), anemia (12% vs 26%), and pneumonia (16% vs 10%). Rash was seen in 18% vs 19% of pts (no grade ≥3 events); 7% of pts in each group had peripheral neuropathy (no grade ≥3 events). There was no evidence of cardiac or renal toxicity with the addition of ixazomib, and no new primary malignancies. Based on an observed higher incidence of herpes zoster reactivation in the IRd treatment group (18%) vs placebo-Rd (0%), the IDMC recommended an antiviral prophylaxis requirement for the entire study population still on treatment; the China continuation protocol was amended accordingly.
Conclusion
In Chinese pts with RRMM, IRd was associated with a significant improvement in PFS, with limited additional toxicity, demonstrating the consistent relative benefit of IRd vs placebo-Rd in this distinct Chinese population and the global study.
Session topic: E-poster
Keyword(s): Myeloma, Oral, Phase III, Proteasome inhibitor
Type: Eposter Presentation
Background
The global, randomized, double-blind, placebo-controlled, phase 3 TOURMALINE-MM1 study (NCT01564537) demonstrated 35% improvement in PFS (HR 0.74, p=0.012) with IRd vs placebo-Rd in pts with RRMM (Moreau et al, ASH 2015).
Aims
This continuation study assessed the efficacy and safety of IRd vs placebo-Rd in pts with RRMM in China as a separate regional expansion of the global study.
Methods
Eligibility criteria and study design were per the global study, except high-risk cytogenetic and patient-reported outcome endpoints were not assessed. The primary endpoint was PFS, assessed by the same independent review committee (IRC) used in the global study. Pts were analyzed separately from the global study. Sample size was not based on a formal statistical hypothesis.
Results
115 pts were randomized and treated (57 IRd, 58 placebo-Rd). Compared to the global study, pts had more advanced disease (63% ISS stage II/III vs 46% in the global study), were more heavily pretreated (60% vs 41% had 2 or 3 prior therapies), had more frequently received prior thalidomide (84% vs 45%), and more frequently had refractory MM (43% vs 11%). At data cut-off (12 July 2015; median follow-up 8.0 vs 7.8 mos for IRd vs placebo-Rd), PFS was significantly improved with IRd vs placebo-Rd: median PFS 6.7 vs 4.0 mos; HR 0.598; 95% CI 0.367–0.972; p=0.035. This benefit was seen across most prespecified subgroups including those with ISS stage I/II at screening, pts who had received 2–3 prior therapies, or prior proteasome inhibitor/IMiD compound therapy. A prespecified sensitivity analysis of PFS according to the EMA censoring rules was consistent with the primary analysis: median PFS 5.8 mos vs 4.0 mos; HR 0.543; 95% CI, 0.340–0.869; p=0.009. TTP was also significantly improved with IRd vs placebo-Rd: median TTP 7.3 vs 4.1 mos; HR=0.583; p=0.032. OS data were not yet mature; 6 (11%) IRd and 16 (28%) placebo-Rd pts have died. The study remains blinded and is ongoing with a final analysis for mature OS data planned. Overall response rate was 56% vs 31% (odds ratio=2.84, p=0.007); the ≥VGPR rate was 25% vs 12%. Among responders, the median duration of response was 7.4 mos with IRd vs 5.6 mos with placebo-Rd. Pts had received a median of 7 and 5 cycles of IRd and placebo-Rd, and 59% and 41% of pts remained on treatment. The median relative dose intensities of all drugs were high (>95%), similar between arms, and consistent with the global study. The overall safety profile was similar in both treatment groups: 56% vs 62% had grade ≥3 AEs, 23% vs 26% had SAEs, 5% vs 12% discontinued treatment due to AEs, and 4% vs 5% died on treatment. Common grade ≥3 AEs with IRd vs placebo-Rd included thrombocytopenia (23% vs 13%), neutropenia (23% vs 19%), anemia (12% vs 26%), and pneumonia (16% vs 10%). Rash was seen in 18% vs 19% of pts (no grade ≥3 events); 7% of pts in each group had peripheral neuropathy (no grade ≥3 events). There was no evidence of cardiac or renal toxicity with the addition of ixazomib, and no new primary malignancies. Based on an observed higher incidence of herpes zoster reactivation in the IRd treatment group (18%) vs placebo-Rd (0%), the IDMC recommended an antiviral prophylaxis requirement for the entire study population still on treatment; the China continuation protocol was amended accordingly.
Conclusion
In Chinese pts with RRMM, IRd was associated with a significant improvement in PFS, with limited additional toxicity, demonstrating the consistent relative benefit of IRd vs placebo-Rd in this distinct Chinese population and the global study.
Session topic: E-poster
Keyword(s): Myeloma, Oral, Phase III, Proteasome inhibitor
Abstract: E1305
Type: Eposter Presentation
Background
The global, randomized, double-blind, placebo-controlled, phase 3 TOURMALINE-MM1 study (NCT01564537) demonstrated 35% improvement in PFS (HR 0.74, p=0.012) with IRd vs placebo-Rd in pts with RRMM (Moreau et al, ASH 2015).
Aims
This continuation study assessed the efficacy and safety of IRd vs placebo-Rd in pts with RRMM in China as a separate regional expansion of the global study.
Methods
Eligibility criteria and study design were per the global study, except high-risk cytogenetic and patient-reported outcome endpoints were not assessed. The primary endpoint was PFS, assessed by the same independent review committee (IRC) used in the global study. Pts were analyzed separately from the global study. Sample size was not based on a formal statistical hypothesis.
Results
115 pts were randomized and treated (57 IRd, 58 placebo-Rd). Compared to the global study, pts had more advanced disease (63% ISS stage II/III vs 46% in the global study), were more heavily pretreated (60% vs 41% had 2 or 3 prior therapies), had more frequently received prior thalidomide (84% vs 45%), and more frequently had refractory MM (43% vs 11%). At data cut-off (12 July 2015; median follow-up 8.0 vs 7.8 mos for IRd vs placebo-Rd), PFS was significantly improved with IRd vs placebo-Rd: median PFS 6.7 vs 4.0 mos; HR 0.598; 95% CI 0.367–0.972; p=0.035. This benefit was seen across most prespecified subgroups including those with ISS stage I/II at screening, pts who had received 2–3 prior therapies, or prior proteasome inhibitor/IMiD compound therapy. A prespecified sensitivity analysis of PFS according to the EMA censoring rules was consistent with the primary analysis: median PFS 5.8 mos vs 4.0 mos; HR 0.543; 95% CI, 0.340–0.869; p=0.009. TTP was also significantly improved with IRd vs placebo-Rd: median TTP 7.3 vs 4.1 mos; HR=0.583; p=0.032. OS data were not yet mature; 6 (11%) IRd and 16 (28%) placebo-Rd pts have died. The study remains blinded and is ongoing with a final analysis for mature OS data planned. Overall response rate was 56% vs 31% (odds ratio=2.84, p=0.007); the ≥VGPR rate was 25% vs 12%. Among responders, the median duration of response was 7.4 mos with IRd vs 5.6 mos with placebo-Rd. Pts had received a median of 7 and 5 cycles of IRd and placebo-Rd, and 59% and 41% of pts remained on treatment. The median relative dose intensities of all drugs were high (>95%), similar between arms, and consistent with the global study. The overall safety profile was similar in both treatment groups: 56% vs 62% had grade ≥3 AEs, 23% vs 26% had SAEs, 5% vs 12% discontinued treatment due to AEs, and 4% vs 5% died on treatment. Common grade ≥3 AEs with IRd vs placebo-Rd included thrombocytopenia (23% vs 13%), neutropenia (23% vs 19%), anemia (12% vs 26%), and pneumonia (16% vs 10%). Rash was seen in 18% vs 19% of pts (no grade ≥3 events); 7% of pts in each group had peripheral neuropathy (no grade ≥3 events). There was no evidence of cardiac or renal toxicity with the addition of ixazomib, and no new primary malignancies. Based on an observed higher incidence of herpes zoster reactivation in the IRd treatment group (18%) vs placebo-Rd (0%), the IDMC recommended an antiviral prophylaxis requirement for the entire study population still on treatment; the China continuation protocol was amended accordingly.
Conclusion
In Chinese pts with RRMM, IRd was associated with a significant improvement in PFS, with limited additional toxicity, demonstrating the consistent relative benefit of IRd vs placebo-Rd in this distinct Chinese population and the global study.
Session topic: E-poster
Keyword(s): Myeloma, Oral, Phase III, Proteasome inhibitor
Type: Eposter Presentation
Background
The global, randomized, double-blind, placebo-controlled, phase 3 TOURMALINE-MM1 study (NCT01564537) demonstrated 35% improvement in PFS (HR 0.74, p=0.012) with IRd vs placebo-Rd in pts with RRMM (Moreau et al, ASH 2015).
Aims
This continuation study assessed the efficacy and safety of IRd vs placebo-Rd in pts with RRMM in China as a separate regional expansion of the global study.
Methods
Eligibility criteria and study design were per the global study, except high-risk cytogenetic and patient-reported outcome endpoints were not assessed. The primary endpoint was PFS, assessed by the same independent review committee (IRC) used in the global study. Pts were analyzed separately from the global study. Sample size was not based on a formal statistical hypothesis.
Results
115 pts were randomized and treated (57 IRd, 58 placebo-Rd). Compared to the global study, pts had more advanced disease (63% ISS stage II/III vs 46% in the global study), were more heavily pretreated (60% vs 41% had 2 or 3 prior therapies), had more frequently received prior thalidomide (84% vs 45%), and more frequently had refractory MM (43% vs 11%). At data cut-off (12 July 2015; median follow-up 8.0 vs 7.8 mos for IRd vs placebo-Rd), PFS was significantly improved with IRd vs placebo-Rd: median PFS 6.7 vs 4.0 mos; HR 0.598; 95% CI 0.367–0.972; p=0.035. This benefit was seen across most prespecified subgroups including those with ISS stage I/II at screening, pts who had received 2–3 prior therapies, or prior proteasome inhibitor/IMiD compound therapy. A prespecified sensitivity analysis of PFS according to the EMA censoring rules was consistent with the primary analysis: median PFS 5.8 mos vs 4.0 mos; HR 0.543; 95% CI, 0.340–0.869; p=0.009. TTP was also significantly improved with IRd vs placebo-Rd: median TTP 7.3 vs 4.1 mos; HR=0.583; p=0.032. OS data were not yet mature; 6 (11%) IRd and 16 (28%) placebo-Rd pts have died. The study remains blinded and is ongoing with a final analysis for mature OS data planned. Overall response rate was 56% vs 31% (odds ratio=2.84, p=0.007); the ≥VGPR rate was 25% vs 12%. Among responders, the median duration of response was 7.4 mos with IRd vs 5.6 mos with placebo-Rd. Pts had received a median of 7 and 5 cycles of IRd and placebo-Rd, and 59% and 41% of pts remained on treatment. The median relative dose intensities of all drugs were high (>95%), similar between arms, and consistent with the global study. The overall safety profile was similar in both treatment groups: 56% vs 62% had grade ≥3 AEs, 23% vs 26% had SAEs, 5% vs 12% discontinued treatment due to AEs, and 4% vs 5% died on treatment. Common grade ≥3 AEs with IRd vs placebo-Rd included thrombocytopenia (23% vs 13%), neutropenia (23% vs 19%), anemia (12% vs 26%), and pneumonia (16% vs 10%). Rash was seen in 18% vs 19% of pts (no grade ≥3 events); 7% of pts in each group had peripheral neuropathy (no grade ≥3 events). There was no evidence of cardiac or renal toxicity with the addition of ixazomib, and no new primary malignancies. Based on an observed higher incidence of herpes zoster reactivation in the IRd treatment group (18%) vs placebo-Rd (0%), the IDMC recommended an antiviral prophylaxis requirement for the entire study population still on treatment; the China continuation protocol was amended accordingly.
Conclusion
In Chinese pts with RRMM, IRd was associated with a significant improvement in PFS, with limited additional toxicity, demonstrating the consistent relative benefit of IRd vs placebo-Rd in this distinct Chinese population and the global study.
Session topic: E-poster
Keyword(s): Myeloma, Oral, Phase III, Proteasome inhibitor
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