Efficacy

NINLARO^® (ixazomib) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

The NINLARO regimen is the only all-oral PI-based triplet approved for treatment to disease progression or unacceptable toxicity^1,7,8

• ^*NINLARO regimen extended median PFS by ~6 months vs the Rd regimen. Median PFS: 20.6 vs 14.7 months for the NINLARO and Rd regimens, respectively; HR=0.74 (95% CI, 0.59-0.94); P=0.012.^1,2
• ^†Results demonstrated in a global, phase 3, randomized, double-blind, placebo-controlled study of patients with relapsed and/or refractory multiple myeloma treated to disease progression or unacceptable toxicity (N=722).^1,2
• ^‡The NINLARO regimen included NINLARO+lenalidomide+dexamethasone. The Rd regimen included placebo+lenalidomide+dexamethasone.
• mPFS=median progression-free survival; NE=not evaluable.

Multiple myeloma is a disease you can't cure, so I think it's important to keep patients on treatment until progression or unacceptable toxicity."
—Dr. Robert Vescio

TOURMALINE-MM1 evaluated long-term* treatment with the all-oral NINLARO^® (ixazomib) regimen

A global, phase 3, randomized, double-blind, placebo-controlled study of patients with relapsed and/or refractory multiple myeloma (N=722)^1,2

• ^*Defined as treatment to disease progression or unacceptable toxicity.
• ^†Stratification: 1 vs 2 or 3 prior therapies; PI exposed vs PI naive; and ISS stage I or II vs III.

• The primary endpoint of PFS, according to 2011 IMWG criteria, was assessed every 4 weeks until disease progression by a blinded IRC and was based on central laboratory results¹
• Key secondary endpoints included OS and OS in del(17p)²
• Other secondary endpoints included ORR, PFS in patients with high-risk cytogenetics,^‡ and safety²
• Patients who were refractory to lenalidomide or PIs were excluded from the study²

• ^‡Defined as patients with del(17p), t(4;14), and/or t(14;16).
  ECOG=Eastern Cooperative Oncology Group performance status; IMWG=International Myeloma Working Group; IRC=independent review committee; ISS=International Staging System; MM=multiple myeloma; ORR=overall response rate; OS=overall survival; PI=proteasome inhibitor.

TOURMALINE-MM1 included difficult-to-treat patients¹

• ^*The NINLARO regimen included NINLARO+lenalidomide+dexamethasone. The Rd regimen included placebo+lenalidomide+dexamethasone.
• ^†Stratification factor.

• Cutoff values for high-risk cytogenetic markers, including del(17p), t(4;14), and t(14;16), were performed by a central laboratory²
• Positivity for del(17p) was defined by a percentage of positive cells that were above the technical background cutoff of 5%²
• Many patients had renal impairment¹
• 23% of patients had light chain disease and 12% of patients had free light chain-measurable only disease¹
• Primary refractory was defined as best response of stable disease or disease progression on all prior lines of therapy. Primary refractory status was documented in 7% and 6% of patients in the NINLARO regimen and the Rd regimen, respectively¹

• Patients who were refractory to lenalidomide or PIs were excluded from the study

When we look at the baseline characteristics as a whole, it's representative of the broad patient population we see in the relapsed setting."
—Dr. Ruben Niesvizky

The NINLARO^® (ixazomib) regimen^* achieved rapid responses^† that deepened with continued treatment^1,2

• ^*The NINLARO (ixazomib) regimen included NINLARO+lenalidomide+dexamethasone.
  The Rd regimen included placebo+lenalidomide+dexamethasone.
  ^†Versus the Rd regimen.
  CR=complete response; ORR=overall response rate; PR=partial response; VGPR=very good partial response.

 

• Depth of response for the NINLARO vs Rd regimens, respectively: ORR^†: 78% vs 72%; CR: 12% vs 7%; VGPR+CR: 48% vs 39%; PR: 30% vs 33%¹
• Responses improved over time in both arms of the study²
• Study limitation: The study was not powered to detect differences in response rates between arms

• ^†ORR=CR+VGPR+PR.

Positive PFS trends seen across selected
prespecified subgroups^2,9,10

• Study limitations:
• This study was not powered to show significance in PFS across these prespecified subgroups⁹
• Cytogenetic risk data were not available for 24% of patients in the study²
• Other prespecified subgroups not included in this figure were gender, race, region, Western countries, prior bortezomib exposure, thalidomide refractory, and creatinine clearance at baseline⁹
• The PFS results in the above subgroups were consistent with those represented in the figure below⁹

• ^*Median PFS (months).
• ^†Defined as patients with del(17p), t(4;14), and/or t(14;16).
• ^‡The NINLARO regimen included NINLARO+lenalidomide+dexamethasone.
• The Rd regimen included placebo+lenalidomide+dexamethasone.
• ECOG=Eastern Cooperative Oncology Group; ISS=International Staging System.

• ^§Defined as patients with del(17p), t(4;14), and/or t(14;16).
  ^‖The NINLARO regimen includes NINLARO+lenalidomide+dexamethasone. The Rd regimen included placebo+lenalidomide+dexamethasone.

Positive PFS trends were seen across certain prespecified subgroups, including patients aged 65 years or younger, those with standard-risk cytogenetics, and those with ECOG 0 or 1.”
—Dr. Antonio Palumbo