Verastem. D.M.B. serves as consultant for, is a member of the scientific advisory board of, and institution is the site of a PI clinical trial (grant paid to the institution) from AbbVie and Genentech.

This study was sponsored by MorphoSys AG.

8020 Background: Patients with R/R DLBCL ineligible for autologous stem cell transplant (ASCT) have a poor prognosis. In these patients, tafasitamab (anti-CD19 antibody) plus lenalidomide (LEN) has shown encouraging results in the open-label, single-arm, phase II L-MIND study (n = 81; NCT02399085). To evaluate the contribution of tafasitamab to the activity of this doublet, we conducted a global, real-world study of patients treated with LEN monotherapy (RE-MIND; NCT04150328). Here we present the primary analysis of a 1:1 patient-level matched comparison between the L-MIND and RE-MIND cohorts. Methods: Patients treated with LEN monotherapy for R/R DLBCL were enrolled in the observational, retrospective RE-MIND cohort. As in L-MIND, patients had 1–3 prior systemic therapies, including ≥1 CD20-targeting regimen; were aged ≥18 years; and were not eligible for ASCT. A 1:1 estimated propensity score (ePS) matching methodology ensured balancing of nine pre-specified baseline covariates. The primary analysis set, Matched Analysis Set 25 (MAS25), included patients who received a LEN starting dose of 25 mg/day. The primary endpoint was investigator-assessed best objective response rate (ORR). Key secondary endpoints included overall survival (OS) and complete response (CR) rate. Results: 490 patients were enrolled in RE-MIND across 58 centers in the US and Europe, of which 140 fulfilled the ePS matching criteria. The MAS25 included 76 patients each from the two cohorts. Baseline characteristics between cohorts were comparable. The primary endpoint was met with a significantly better ORR of 67.1% (95% CI: 55.4–77.5) for the L-MIND cohort versus 34.2% (95% CI: 23.7–46.0) for the RE-MIND cohort (odds ratio 3.89; 95% CI: 1.90–8.14; p < 0.0001). The CR rate was 39.5% (95% CI: 28.4–51.4) in the L-MIND cohort and 13.2% (95% CI: 6.5–22.9) in the RE-MIND cohort. A significant difference in OS favored the L-MIND cohort (HR = 0.499; 95% CI: 0.317–0.785). ORR and CR outcomes in the RE-MIND cohort were similar to the published literature for LEN monotherapy in R/R DLBCL. Conclusions: Significantly better ORR, CR and OS indicate potential synergistic effects of the tafasitamab + LEN combination in ASCT-ineligible R/R DLBCL. ePS-based 1:1 matching allows robust estimation of the treatment effect of tafasitamab when added to LEN. RE-MIND demonstrates the utility of real-world data in interpreting non-randomized trials. Clinical trial information: NCT04150328 .

IntroductionCarboplatin is widely used to treat lung cancer in the United States as an alternative to cisplatin. Several studies have demonstrated that cisplatin-based regimen is associated with a high frequency of thromboembolic complications. However, there has been limited investigation directly comparing the risk of thromboembolic events (TEEs) between cisplatin- and carboplatin-treated patients with lung cancer.MethodsAll lung cancer patients treated with cisplatin or carboplatin at Wilmot Cancer Center, University of Rochester between 2011 and 2014 were included. Patient characteristics including exposure (cisplatin vs. carboplatin) and outcome (TEEs between the time of the first dose of cisplatin or carboplatin and 4 weeks after the last dose) were collected by reviewing electronic medical records. A Fisher’s exact test was used to compare the proportion of incident TEEs between cisplatin and carboplatin groups. The risk of TEE associated with carboplatin compared to cisplatin was assessed using multiple logistic regression.ResultsAmong 415 subjects, 317 patients (76.4%) received carboplatin and 98 (23.6%) patients received cisplatin. In the carboplatin group, 10.9% (33/302) of evaluable patients developed treatment-related TEEs vs. 14.7% (14/95) in the cisplatin group. There was no significant difference in the risk of developing TEEs between the two groups (P = 0.32). However, 15.2% of carboplatin-related TEEs were arterial thromboses compared to none in the cisplatin group.ConclusionsThe incidence of carboplatin-related TEEs was high in lung cancer patients without significant difference in the risk of developing TEEs between cisplatin and carboplatin groups. Potential use of prophylactic anticoagulation in all platinum-treated patients should be further investigated.

Background Lesinurad (LESUR) is an oral investigational URAT1 inhibitor for the treatment of gout. A Phase 2B study in 208 gout patients with an inadequate response to allopurinol (ALLO) (200-600 mg/day for ≥6 weeks) demonstrated that the combination of LESUR+ALLO resulted in superior reductions in sUA with 79%, 74%, and 63% of patients achieving sUA <6 mg/dL after 28 days of dosing with 600 mg, 400 mg and 200 mg LESUR, respectively, compared to 25% with placebo (PBO)+ALLO (p<0.0001 for all comparisons). Subjects completing the Phase 2B study could enter a 44-week, blinded, PBO-controlled extension, the results of which are presented here. Objectives To assess the ongoing efficacy and safety of LESUR in combination with ALLO vs. PBO+ALLO in patients with an inadequate response to standard doses of ALLO. Methods Subjects completing the double-blind 28-day main study were washed out of LESUR or PBO before entering the blinded extension period, but remained on a stable dose of ALLO. Subjects then restarted their original blinded treatment of LESUR or PBO. All LESUR-treated subjects started on the 200 mg dose and were to have the dose titrated stepwise to 400 or 600 mg if the sUA was not <5 mg/dL. After dose escalation of LESUR or PBO, ALLO dose could be escalated. Results 126 subjects enrolled into the blinded extension study (78 LESUR and 48 PBO); 91 subjects completed 44 weeks at time of this analysis. 78% of LESUR treated subjects maintained sUA <6 mg/dL at 44 weeks, compared to 56% of PBO subjects (LOCF analysis); 59% of subjects receiving LESUR also achieved sUA<5 mg/dL compared to 25% of PBO subjects. ALLO doses were increased in the majority of PBO subjects. 29 subjects (13 PBO/16 LESUR) withdrew from the study for any reason before Week 44. Overall rates of adverse events (AEs) were low and similar between the treatment groups. 4 subjects reported serious AEs (angina pectoris, cerebral artery embolism, tendon rupture, bursitis infective) considered not related to treatment. Transient serum creatinine (sCr) elevations were observed in both groups; on LESUR these generally occurred early or after dose escalations and usually resolved to within the normal range while on LESUR. 4 subjects discontinued due to increased sCr; 1 receiving PBO and 3 on LESUR. Monthly gout flare rates for subjects remaining on the 200 mg dose were generally lower for the LESUR group compared to PBO during Months 7-12. Conclusions In patients who do not respond adequately to ALLO, the addition of LESUR produced consistent, sustained reductions in sUA levels, with the majority of subjects achieving sUA levels of <6 mg/dL and <5 mg/dL. Despite dose increases of ALLO in the majority of PBO subjects, combination therapy was superior. LESUR was well-tolerated with a similar rate of AEs to placebo. The premature discontinuation rate on PBO was higher than on LESUR. LESUR is a promising investigational drug for the treatment of hyperuricemia in gout patients. Disclosure of Interest F. Perez-Ruiz Grant/Research support from: Asociaciόn de...