Citations

SummaryDespite the absence of high‐risk cytogenetics and lower International Staging System (ISS) stages, a subset of patients with multiple myeloma (MM) experience poor overall survival (OS). We studied 1461 patients with newly diagnosed MM to identify patient and disease characteristics that predict a high‐risk phenotype among standard‐risk patients. Fifty‐six percent of all patients presented with standard‐risk disease. Among them, advanced age, extremes of body mass index, non‐hyperdiploid karyotype and abnormal lymphocyte counts were associated with worse OS. Standard‐risk patients with 0–1 of these adverse factors (hazard ratio [HR] 0·32, 95% confidence interval [CI] 0·24–0·43, P < 0·001) and 2 adverse factors (HR 0·54, 95% CI 0·41–0·72, P < 0·001) experienced better OS than high‐risk patients. Two or more adverse factors were present in 17% of standard‐risk patients and were associated with OS comparable to high‐risk patients (HR 0·91, 95% CI 0·67–1·24, P = 0·548). Predictive power among standard‐risk patients was improved using score groups compared to ISS stages. Patients with standard‐risk MM are a heterogeneous group with one in six patients experiencing OS comparable to high‐risk disease. Patients at risk can be identified using readily available patient and disease characteristics. These findings emphasize the importance of accurate risk stratification and help explain part of the heterogeneity observed in clinical practice.

SummaryBackgroundGastroparesis has a significant negative impact on patients’ quality of life. Only one medication is approved for gastroparesis and it is associated with a significant risk of side effects.AimTo assess the willingness of patients to take risks associated with medications to treat gastroparesis symptoms.MethodsWe developed a questionnaire to assess medication risk‐taking behaviour in patients identified as having documented gastroparesis (consistent symptoms, normal upper endoscopy, delayed gastric emptying). The survey assessed demographics, symptoms, medication use, anxiety, depression and impulsivity. A standard reference gamble evaluated respondents’ willingness to take medication risks.ResultsTwo hundred seven questionnaires were mailed to patients, 103 questionnaires were completed. Seventy‐six percent were female; the mean age was 48 years; average duration of gastroparesis symptoms was 10 years. Self‐reported symptom severity was severe in 52% and moderate in 32%. Gastroparesis patients reported that they would accept a median 13.4% risk of sudden death to cure their symptoms using a hypothetical medication. Self‐reported gastroparesis symptom severity and Gastroparesis Cardinal Symptom Index scores correlated significantly with increased willingness to take risks associated with medications to treat gastroparesis, while anxiety was negatively associated.ConclusionsGastroparesis patients are willing to accept markedly high risks with a hypothetical medication to cure their symptoms. Patients with severe gastroparesis symptoms and higher Gastroparesis Cardinal Symptom Index scores were more willing to take these risks. This study, the first to quantify gastroparesis patients’ willingness to accept medication associated risks, should help clinicians through the complex maze of gastroparesis therapies and their associated risks and benefits.

208 Background: PEGPH20 degrades hyaluronan (HA), a major component of the stroma, increases delivery of gemcitabine and prolongs survival in preclinical models. We evaluated the activity of PEGPH20 in combination with mFFOX in mPC , unselected for tumor HA. Methods: Pertinent eligibility: untreated mPC, PS of 0-1 and adequate organ function. Standard FFOX was modified to add prophylactic growth factor support and omit bolus 5FU. Due to increased thromboembolic (TE) events with PEGPH20, an amendment instituted LMWH prophylaxis in the PEGPH20 arm only. Following a dose finding cohort of mFFOX + PEGPH20, the Phase II study randomized patients (1:1) to the combination arm or mFFOX alone (n = 138). The primary endpoint was overall survival (OS), with a null median OS of 10 mo and an alternative of 15 mo (1-sided type 1 error 0.1, 80% power). Results: PEGPH20 at 3 mcg/kg, q2 weeks was more tolerable than twice weekly dosing. The randomized phase II study began May 2015. The planned interim futility analysis when 35 deaths occurred gave a HR of 0.44 favoring the standard arm, thus the study was closed to accrual (March 2017). As of August 22, 2017 (n = 111), the estimated median OS in the mFFOX arm was 15.1 mo (95% CI 10.1-15.7) vs 7.6 mo (95% CI 4.6-9.2) in the PEGPH20 arm. Conclusions: OS in the mFFOX control arm (15.1 mo) is longest yet reported. Addition of PEGPH20 to mFFOX is not recommended for further study and appears to be detrimental (HR = 0.48). The impact of PEGPH20 on OS was unexpected and in contrast to favorable results reported for the combination of gemcitabine/nab-paclitaxel + PEGPH20 especially in the HA high cohort (Hingorani S et al. A 4008, ASCO 2017). PEGPH20 with mFFOX caused increased toxicity (mostly GI and TE events) and decreased treatment duration compared to mFFOX alone. Tumor HA content will be analyzed. Funding: NIH/NCI grants CA180888, CA180819; and in part by Halozyme Inc. Clinical trial information: 01959139. [Table: see text]