Ninreal - a Real World (RW) Comparison of Ixazomib Triplets and IMiD Duplets, in Relapsed and Refractory Multiple Myeloma (RRMM) from the Austrian Myeloma Registry (AMR)

Introduction:

Recent analyses confirm the high potential of Ixazomib (I) based therapies in RRMM to be upheld for prolonged periods often achieving superior clinical long-term results compared to various comparators. Our analysis compares I-based triplets vs. IMiD doublets; ixazomib, lenalidomide and dexamethasone (IRd) vs. lenalidomide and dexamethasone (Rd); ixazomib, pomalidomide and dexamethasone (IPd) vs. pomalidomide and dexamethasone (Pd) in patients with relapsed and refractory Multiple Myeloma (RRMM) in clinical routine .

Methods:

Pts. treated with the target regimens between NOV 15 and MAR 22 in any line of treatment (LoT) beyond first line were identified via the AMR. The primary endpoint was defined the median time-to-next-treatment (TTNT) achieved with either IRd. Rd ,IPd and Pd in RRMM settings, while secondary endpoints used were median response rates (RR), median overall survival (OS) and safety.

Results:

284 RRMM pts. were recruited. 52 pts. received IRd, 124 pts. with Rd, 32 received IPd and 76 pts. a Pd doublet. With view to basic epidemiologic characteristics as age and sex distribution, as well as myeloma characteristics as isotype-, and light chain patterns, cytogenetics, frequency of extramedullary disease, and ISS stage distribution the cohort shows a pattern well in-line with other big epidemiologic analyses. Slightly less than half of pts. received the index treatment in 2^nd LoT, and over 2/3 of pts. in either 2^nd or 3^rd LoT. Nearly all pts. were pretreated with PIs, mostly bortezomib (88.2% - 95.2%). IMiD pretreatment with either R, T (thalidomide), or P was also frequent, but slightly less common in the 4 subgroups (58.2% - 67%). Not surprisingly pts. receiving doublets had a higher median age and a reduced performance status (ECOG 2 or higher) was observed more frequently in this group, than in pts. treated with triplets.

In both triplets (IPd, IRd) a median RR of ~82% could be observed compared to ~74% in the doublet regimes (Rd, Pd). Also triplets resulted in higher quality responses (VGPR or better in 43% vs. 30%), while on the response category level no differences between IRd and IPd could be observed. With respect to median TTnT and OS IRd outperformed all other treatment approaches considerably: median TTnT 16.5 mo.(IRd), 10.5 mo.(Rd), 12.5 mo. (IPd) and 8 mo.(Pd), as well as an observed median OS of 34.5 mo. vs. 25 mo., vs. 29 mo., vs. 23.5 mo. respectively. These results are all the more impressive seeing the extremely high proportion of pts. pre-treated with both PIs and IMiDs. Dose modifications were slightly less frequently seen with R vs. P-based regimes and doublets vs. triplets. All differences though were minor. Results of a multivariate analysis will be presented.

Discussion:

The data generated within the NINREAL analysis fits very well in the landscape of other RW analyses covering I-based therapies in RRMM, mainly in 2^nd and 3^rd line. Outcomes with IRd were promising although pre-treatment with both PIs (usually bortezomib) and IMiDs (usually R) was frequent. An OS of ~ 3 years was documented both in our and the Czech analysis. RW results for other proteasome inhibitor based triplets or P-based-triplets were not found to be superior, but these were pre-dominantly used in more advanced and higher risk, but younger pts.. Bullet Points

- I - based triplets are valid therapeutic options in RRMM

- I - based triplets are safe and manageable over prolonged periods of time

- I - based triplets work also in pts. pre-exposed to both IMiDs and PIs

- A median TTnT of 16.5 mo. and a median OS of 34,5 mo. was achieved with IRd in NINREAL- Due to small numbers anddivergent pt. populations the inferior outcomes with IPd should be interpreted cautiously

Willenbacher:Fujimoto: Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Sandoz: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Merck: Consultancy; Morphosys: Consultancy, Other: Safety and Steering Committees; Novartis: Consultancy, Honoraria, Research Funding; Kite: Consultancy; Incyte: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria; Gilead: Consultancy, Honoraria; EUSA Pharma: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: Steering and Safety Committees, Research Funding; syndena GmbH: Current Employment; Takeda: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Honoraria, Other: Steering and Safety Committees, Research Funding; Myelom- und Lymphomselbsthilfe Österreich: Honoraria; oncotyrol: Research Funding; DSMM: Other: Safety and Steering Committees. Pichler:amgen: Honoraria; gilead: Honoraria; janssen: Honoraria; sanofi: Honoraria; takeda: Honoraria. Krauth:AMGEN: Honoraria; Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria; GSK: Honoraria; BMS-Celgene: Honoraria; Takeda: Honoraria. Agis:Takeda: Honoraria; BMS: Honoraria; AMGEN: Honoraria; Janssen: Honoraria, Research Funding. Hartmann:BMS: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Janssen CIlag: Honoraria. Podar:Celgene: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy; Roche: Other: Research support. Weger:syndena GmbH: Current Employment.

The breakdown of real-world treatments includes an un licensed combination: Ixazomib, Pomalidomide and Dexamethasone (IPd)