PF729 LONG‐TERM PROTEASOME INHIBITION (LTPI) IN PATIENTS (PTS) WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): US MM‐6, A REAL‐WORLD (RW) STUDY TRANSITIONING FROM BORTEZOMIB (BTZ) TO IXAZOMIB (IXA)
Authors: Rifkin R.M. , Yimer H.A. , Noga S.J. , Manda S. , Birhiray R. , Yasenchak C. , Lyons R. , Kelly P. , Chojnicki E. , Whidden P. , Wang B. , Demers B. , Dollar L. , Boccia R. 
Published: June 2019

Background:LTPI improves outcomes in NDMM vs non‐proteasome inhibitor (PI)–based therapy. However, the efficacy improvements seen in clinical trials are often not achieved in real‐world settings and duration of PI‐based therapy is typically shorter in US non–transplant NDMM RW pts (Niesvizky 2015) vs in phase 3 trials (San Miguel 2008; Mateos 2018). This may be due to poor treatment adherence, burden of repeated parenteral administration (which can negatively impact quality of life [QoL]), comorbidities, financial burden, distance from treatment center, physician/pt preference, or toxicity (eg peripheral neuropathy [PN] with btz, which can worsen with prolonged exposure and lead to discontinuation) (Richardson 2018). Maintaining QoL, minimizing toxicity and increasing adherence are critical for NDMM pts receiving LTPI. US MM‐6 is a RW US community‐based phase 4 study investigating transitioning from a parenteral PI (btz) to an oral PI (ixa) in NDMM to increase PI‐based treatment adherence and duration, maintain QoL and improve outcomes.Aims:We report preliminary demographics, baseline disease characteristics, actigraphy and electronic pt–reported outcomes (ePRO) compliance data for US MM‐6 pts receiving all‐oral ixa–lenalidomide‐dexamethasone (IRd).Methods:US MM‐6 (NCT03173092) is enrolling ∼160 non‐transplant pts (transplant‐ineligible or transplant delayed >24 months) with ≥stable disease after 3 cycles of a btz‐based induction, at ∼30 community sites. Pts receive IRd (ixa 4 mg on day 1, 8, and 15, lenalidomide 25 mg on days 1–21, dexamethasone 40 mg [20 mg for pts aged >75 years] on day 1, 8, 15, and 22, of each 28‐day cycle) until progression or toxicity for ≤26 cycles. QoL and monthly medication adherence are assessed via ePROs. Pts use wearable digital devices and smartphones to inform on their experience with an all‐oral PI‐based regimen by recording daily pt‐reported medication adherence and actigraphy (average activity [steps], total sleep and deep sleep time per day). Primary endpoint: progression‐free survival (PFS); secondary endpoints: response, duration of therapy, ePRO compliance, overall survival (OS), and safety. We report preliminary data for the first 25 patients enrolled.Results:At data cutoff, 80% of pts were aged ≥65 years, 40% were male, 3/23 (13%) were of non‐white race, 16% were of Hispanic/Latino ethnicity, and 9/21 (43%) had International Staging System stage III disease. Comorbidities included renal and urinary disorders (48%), PN (28%), and cardiac disorders (24%). At data cutoff, 3 (12%) pts had discontinued study treatment due to pt/physician preference. Pts have received a median of 5 (range 1–12) cycles of IRd to date (plus 3 cycles of pre‐enrollment btz‐based therapy). Average ePRO compliance was 92% (Figure). At data cutoff, 24 pts recorded actigraphy data (2086 compliant days [≥12 hours of data]); mean (standard deviation) number of steps/day and total sleep time were 3236 (3540) and 8.35 (3.21) hours, respectively. Response, PFS, and OS were not available at data cutoff.Summary/Conclusion:Duration of PI‐based therapy is similar to previously published reports of LTPI; US MM‐6 pts are older with a higher rate of advanced stage disease vs previous LTPI studies, yet have high compliance rates. US MM‐6 will provide useful data on pt/disease characteristics and outcomes, including QoL and actigraphy, for IRd‐treated US NDMM RW pts receiving LTPI.image