Search

Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018–2020) were performed to identify randomized clinical trials (RCTs) and real-world studies in NDMM reporting median PFS and objective response. Associations between PFS and each response endpoint were evaluated using Pearson's product-moment correlation weighted by sample size in each RCT arm. Unadjusted and adjusted weighted linear regression models were applied to estimate the gain in median PFS associated with each response endpoint. Statistically significant correlations were identified for median PFS with overall response rate (ORR; Pearson r = 0.59), CR (r = 0.48), stringent CR (sCR; r = 0.68), and MRD (r = 0.69). The unadjusted models estimated 0.50 (95% CI: 0.36, 0.64; p<0.001), 0.42 (95% CI: 0.25, 0.58; p<0.001), 1.05 (95% CI: 0.58, 1.52; p<0.001), and 0.35 (95% CI: 0.12, 0.58; p = 0.006) months of median PFS gained per point of ORR, CR, sCR, and MRD, respectively. Associations for median PFS remained statistically significant in models adjusted for age and treatment type with ORR (0.35, 95% CI: 0.21, 0.49; p<0.001), and adjusted for age and International Staging System risk stage with CR (0.29, 95% CI: 0.16, 0.41; p<0.001). Due to small sample size, adjusted models could not be constructed for sCR or MRD. Nevertheless, evidence of significant survival benefit (p<0.05) associated with MRD negativity and sCR was identified across real-world studies. These findings provide support for the use of response outcomes as surrogate endpoints to estimate PFS benefit in NDMM. [ABSTRACT FROM AUTHOR]

Patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) can be effectively treated with tyrosine kinase inhibitors (TKIs) and achieve a lifespan similar to the general population. The success of TKIs, however, requires long-term and sometimes lifelong treatment; thus, patient-assessed health-related quality of life (HRQoL) has become an increasingly important parameter for treatment selection. Bosutinib is a TKI approved for CP CML in newly diagnosed adults and in those resistant or intolerant to prior therapy. In the Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment (BFORE), bosutinib demonstrated a significantly higher major molecular response rate compared with imatinib, with maintenance of HRQoL (measured by the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire), after 12 months of first-line treatment. We examined relationships between molecular response (MR) and HRQoL. MR values were represented by a log-reduction scale (MRLR; a continuous variable). A repeated-measures longitudinal model was used to estimate the relationships between MRLR as a predictor and each FACT-Leu domain as an outcome. Effect sizes were calculated to determine strength of effects and allow comparisons across domains. The majority of FACT-Leu domains (with the exception of social well-being and physical well-being) demonstrated a significant relationship with MRLR (p < 0.05). Our results showed variable impact of clinical improvement on different dimensions of HRQoL. For patients who achieved MR5, emotional well-being and leukemia-specific domains showed the greatest improvement, with medium differences in effect sizes, whereas social well-being and physical well-being had the weakest relationship with MR. [ABSTRACT FROM AUTHOR]

Background: Most psoriasis patients have mild to moderate disease, commonly treated topically. Current topical agents have limited efficacy and undesirable side effects associated with long-term use. Tofacitinib is a small molecule Janus kinase inhibitor investigated for the topical treatment of psoriasis. Methods: This was a 12-week, randomized, double-blind, parallel-group, vehicle-controlled Phase 2b study of tofacitinib ointment (2 % and 1 %) applied once (QD) or twice (BID) daily in adults with mild to moderate plaque psoriasis. Primary endpoint: proportion of patients with Calculated Physician's Global Assessment (PGA-C) clear or almost clear and ≥2 grade improvement from baseline at Weeks 8 and 12. Secondary endpoints: proportion of patients with PGA-C clear or almost clear; proportion achieving Psoriasis Area and Severity Index 75 (PASI75) response; percent change from baseline in PASI and body surface area; change from baseline in Itch Severity Item (ISI). Adverse events (AEs) were monitored and clinical laboratory parameters measured. Results: Overall, 435 patients were randomized and 430 patients received treatment. The proportion of patients with PGA-C clear or almost clear and ≥2 grade improvement from baseline at Week 8 was 18.6 % for 2 % tofacitinib QD (80 % confidence interval [CI] for difference from vehicle: 3.8, 18.2 %) and 22.5 % for 2 % tofacitinib BID (80 % CI: 3.1, 18.5 %); this was significantly higher vs vehicle for both dosage regimens. No significant difference vs vehicle was seen at Week 12. Significantly more patients achieved PGA-C clear or almost clear with 2 % tofacitinib QD and BID and 1 % tofacitinib QD (not BID) at Week 8, and with 2 % tofacitinib BID at Week 12. Pruritus was significantly reduced vs vehicle with 2 % and 1 % tofacitinib BID (starting Day 2), and 2 % tofacitinib QD (starting Day 3). Overall, 44.2 % of patients experienced AEs, 8.1 % experienced application site AEs, and 2.3 % experienced serious AEs. The highest incidence of AEs (including application site AEs) was in the vehicle QD group. Conclusions: In adults with mild to moderate plaque psoriasis, 2 % tofacitinib ointment QD and BID showed greater efficacy than vehicle at Week 8, but not Week 12, with an acceptable safety and local tolerability profile. [ABSTRACT FROM AUTHOR]