Kumar, Arun

AbstractPatient‐reported outcomes in AL amyloidosis have not been well‐studied. We analyzed health‐related quality of life (HRQOL) and AL amyloidosis symptoms data from the phase 3 TOURMALINE‐AL1 trial (NCT01659658) (ixazomib‐dexamethasone, n = 85; physician's choice of chemotherapy [PC], n = 83). HRQOL and symptom burden were measured with the SF‐36v2, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG‐Ntx), and an amyloidosis symptom questionnaire (ASQ). Score changes during treatment were analyzed descriptively and using repeated‐measures linear mixed models; analyses were not adjusted for multiplicity. Least‐squares (LS) mean changes from baseline were significantly higher (better HRQOL) for ixazomib‐dexamethasone at several cycles for SF‐36v2 Role Physical and Vitality subscales (p < .05); no subscales demonstrated significant differences favoring PC. For FACT/GOG‐Ntx, small but significant differences in LS mean changes favored ixazomib‐dexamethasone over PC at multiple cycles for seven items and both summary scores; significant differences favored PC for one item (trouble hearing) at multiple cycles. ASQ total score trended downward (lower burden) in both arms; significant LS mean differences favored ixazomib‐dexamethasone over PC at some cycles (p < .05). Patients with relapsed/refractory AL amyloidosis treated with ixazomib‐dexamethasone experienced HRQOL and symptoms that were similar to or trended better than patients treated with PC despite longer duration of therapy.

8546 Background: The PI bortezomib is commonly used in first-line therapy of AL, but new therapies are needed that are tolerable in the context of multi-organ dysfunction and that, in RRAL, offer improved outcomes following prior bortezomib. Ixazomib is an oral PI, and in TOURMALINE-AL1, the first phase 3 trial conducted in RRAL, while the first primary endpoint of hematologic overall response rate (ORR) was not met, all clinically relevant time-to-event endpoint data favored Ixa-Dex vs PC (Dispenzieri et al, ASH 2019). Methods: RRAL pts with 1–2 prior therapies were randomized (1:1) to Ixa-Dex (n = 85) or PC (n = 83; Dex plus lenalidomide [n = 47], melphalan [n = 24], cyclophosphamide [n = 10], or thalidomide [n = 2]), stratified by cardiac stage, relapsed vs refractory disease, and prior PI exposure. The primary endpoints were hematologic ORR and 2-yr rate of vital organ deterioration or death. We report subgroup analyses of ORR and outcomes by prior PI exposure. Results: Of the 168 pts enrolled, 90 were PI-naïve and 78 PI-exposed (46 and 39 in the Ixa-Dex arm; 44 and 39 in the PC arm) per stratification; 28 and 27 pts in the Ixa-Dex and PC arms had received bortezomib in their last prior line. Hematologic ORR was 63% vs 50% for Ixa-Dex vs PC (odds ratio [OR] 1.71; 95% confidence interval [CI] 0.74–3.96) in PI-naïve pts, and 41% vs 51% (OR 0.66; 95% CI 0.27–1.62) in PI-exposed pts. For time-to-event outcomes (Table), hazard ratios (HRs) were 0.46–0.85 in favor of Ixa-Dex vs PC in both PI-naïve and PI-exposed pts. Conclusions: Hematologic ORR was higher with Ixa-Dex vs PC in PI-naïve pts but lower in PI-exposed pts (although not statistically significant), and long-term clinically relevant outcomes favored Ixa-Dex in both groups. Based on HRs, the magnitude of benefit appeared similar or greater in PI-naïve vs PI-exposed pts. Clinical trial information: NCT01659658 . [Table: see text]