Yanyan Zhu

Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens

PURPOSEnThe US community-based, phase IIIB UPFRONT trial was designed to compare three frontline bortezomib-based regimens in transplantation-ineligible patients with myeloma.nnnPATIENTS AND METHODSnPatients (N = 502) were randomly assigned 1:1:1 to 24 weeks (eight 21-day cycles) of induction with bortezomib-dexamethasone (VD; n = 168; intravenous bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11 plus oral dexamethasone 20 mg, days 1, 2, 4, 5, 8, 9, 11, and 12 [cycles 1 to 4], or 1, 2, 4, and 5 [cycles 5 to 8]), bortezomib-thalidomide-dexamethasone (VTD; n = 167; bortezomib and dexamethasone as before plus oral thalidomide 100 mg, days 1 to 21), or bortezomib-melphalan-prednisone (VMP; n = 167; bortezomib as before plus oral melphalan 9 mg/m(2) and oral prednisone 60 mg/m(2), days 1 to 4, every other cycle), followed by 25 weeks (five 35-day cycles) of bortezomib maintenance (1.6 mg/m(2), days 1, 8, 15, and 22). The primary end point was progression-free survival.nnnRESULTSnAfter 42.7 months median follow-up, median progression-free survival with VD, VTD, and VMP was 14.7, 15.4, and 17.3 months, respectively; median overall survival was 49.8, 51.5, and 53.1 months, with no significant differences among treatments for either end point (global P = .46 and P = .79, respectively, Wald test). Overall response rates were 73% (VD), 80% (VTD), and 70% (VMP). Adverse events were more common with VTD than VD or VMP. Bortezomib maintenance was feasible without producing cumulative toxicity.nnnCONCLUSIONnAlthough all bortezomib-containing regimens produced good outcomes, VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice.

Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma

Brentuximab vedotin (BV) significantly improved progression‐free survival in a phase 3 study in patients with relapsed or refractory Hodgkin lymphoma (RR‐HL) post‐autologous‐haematopoietic stem cell transplant (auto‐HSCT); we report the impact of BV on quality of life (QOL) from this trial. The European Quality of Life five dimensions questionnaire was administered at the beginning of each cycle, end of treatment, and every 3 months during follow‐up; index value scores were calculated using the time trade‐off (TTO) method for UK‐weighted value sets. Questionnaire adherence during the trial was 87·5% (N = 329). In an intent‐to‐treat analysis, compared with placebo, TTO scores in the BV arm did not exceed the minimally important difference (MID) of 0·08 except at month 15 (−0·084; 95% confidence interval, −0·143 to −0·025). On‐treatment index scores were similar between arms and did not reach the MID at any time point; mixed‐effect modelling showed that BV treatment effect was not significant (P = 0·2127). BV‐associated peripheral neuropathy did not meaningfully impact QOL. Utility scores for patients who progressed declined compared with those who did not; TTO scores between these patients exceeded the MID beginning at month 15. In conclusion, QOL decreased modestly with BV consolidation treatment in patients with RR‐HL at high risk of relapse after auto‐HSCT.

Patient-reported health-related quality of life from the phase III TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone versus placebo-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma

TOURMALINE‐MM1 is a phase III, randomized, double‐blind, placebo‐controlled study of ixazomib plus lenalidomide and dexamethasone (IRd) versus placebo‐Rd in patients with relapsed/refractory multiple myeloma following 1–3 prior lines of therapy. The study met its primary endpoint, demonstrating significantly longer progression‐free survival (PFS) in the IRd arm versus placebo‐Rd arm (median 20.6 vs 14.7 months, hazard ratio 0.74, Pu2009=u2009.01), with limited additional toxicity. Patient‐reported health‐related quality of life (HRQoL) was a secondary endpoint of TOURMALINE‐MM1. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core‐30 (QLQ‐C30) and Multiple Myeloma Module 20 (QLQ‐MY20) were completed at screening, the start of cycles 1 and 2, every other cycle, the end of treatment, and every 4 weeks until progression. Over median follow‐up of 23.3 and 22.9 months in the IRd and placebo‐Rd arms, mean QLQ‐C30 global health status (GHS)/QoL scores were maintained from baseline over the course of treatment in both groups, with no statistically significant differences between groups. EORTC QLQ‐C30 function domain scores were also generally maintained from baseline; similarly, physical, emotional, and social function domains were maintained with IRd versus placebo‐Rd, with slightly higher mean change from baseline scores at earlier time points with IRd. Findings from this double‐blind study demonstrate that addition of ixazomib to Rd significantly improved efficacy while HRQoL was maintained, reflecting the limited additional toxicity seen with IRd versus placebo‐Rd, and support the feasibility of long‐term IRd administration.

Clinical and economic burden of peripheral T-cell lymphoma in commercially insured patients in the United States: findings using real-world claims data.

Abstract Objective: This retrospective cohort study utilized real-world claims data to assess the clinical and economic burden of peripheral T-cell lymphoma (PTCL) over the continuum of care in the US. Methods: Data were extracted from US administrative claims databases to identify adult patients with PTCL (ICD-9-CM code 202.7X) diagnosed between October 2007 and June 2011. Patients had to have ≥6 months of continuous enrollment before and ≥12 months of continuous enrollment after their index date (date of first PTCL diagnosis). PTCL patients were matched (1:5) by age, sex, region, plan type, payer type, and length of continuous enrollment, to a control group of randomly selected patients without PTCL. Patient-level healthcare resource utilization data and associated costs (in US dollars) were measured. Mean costs per patient per month were determined. Results: Of 2820 patients with PTCL, 1000 met all inclusion criteria (median ageu2009=u200957 years; 57.5% male) and were matched to the control group (nu2009=u20095000). On an average monthly basis, PTCL patients were hospitalized more frequently (0.07 vs 0.01 admissions; pu2009<u20090.0001) and had a longer length of hospital stay (6.4 vs 4.0 days; pu2009<u20090.0001) compared with controls. PTCL patients also had higher monthly utilization of pharmacy services (2.85 vs 0.97 prescriptions; pu2009<u20090.0001), office visits (1.35 vs 0.34 visits; pu2009<u20090.0001), ER visits (0.07 vs 0.02 visits; pu2009<u20090.0001), hospice stays (0.05 vs 0.01 stays; pu2009<u20090.0001) and other patient services/procedures. Overall, PTCL patients incurred higher average monthly costs per patient compared with control patients (

Brentuximab vedotin consolidation post-autologous stem cell transplant in Hodgkin lymphoma patients at risk of residual disease: number needed to treat

6327.84 vs

Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma

388.39; pu2009<u20090.0001), driven mainly by hospitalizations (32.2% of overall costs) and pharmacy services (19.6%). Conclusions: This is the first real-world study to quantify healthcare resource utilization, costly treatment, and overall medical expenditure in commercially insured PTCL patients. Better tolerated and more effective treatments may improve disease management and reduce the clinical and economic burden of PTCL.

Brentuximab vedotin (BV) consolidation post-autologous stem cell transplant (ASCT) in patients (pts) with Hodgkin lymphoma (HL) at risk of residual disease: Number needed to treat (NNT) analysis.

Abstract The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8u2009mg/kg (nu2009=u2009165) or placebo (nu2009=u2009164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18–6.07 for patients with ≥2 risk factors, and 2.98–5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3–8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin.

Quality of life EQ-5D results from the AETHERA trial: A phase III study of brentuximab vedotin consolidation following autologous stem cell transplant for HL.

Abstract Aims: The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM). Methods: In this double-blind, placebo-controlled, randomized study (NCT01564537), 722 patients with RRMM following 1–3 prior lines of therapy received Rd plus ixazomib (ixazomib-Rd; nu2009=u2009360) or matching placebo (placebo-Rd; nu2009=u2009362) until disease progression or unacceptable toxicity. Healthcare resource utilization data were captured on Day 1 of each 28-day cycle, every 4 weeks during follow-up for progression-free survival, and every 12 weeks during subsequent follow-up, and included medical encounters (length of stay, inpatient, outpatient, and reason) and number of missing days from work or other activities for patients and caregivers. Results: Exposure-adjusted rates of hospitalization were similar between the ixazomib-Rd and placebo-Rd arms, at 0.530 and 0.564 per patient year (ppy), respectively, as were outpatient visit rates (3.305 and 3.355 ppy). Mean length of hospitalization per patient was 10.0 and 10.8 days, respectively. In both arms, hospitalization and outpatient visit rates were higher in patients with two or three prior lines of treatment (ixazomib-Rd: 0.632 and 3.909 ppy; placebo-Rd: 0.774 and 3.539 ppy) compared with patients with one prior line (ixazomib-Rd: 0.460 and 2.888 ppy; placebo-Rd: 0.436 and 3.243 ppy). Patients and their caregivers who missed any work or other activity missed a median of 7 and 5 days in the ixazomib-Rd arm, respectively, vs 8 and 4 days with placebo-Rd. Limitations: The study was not powered for a statistical comparison of healthcare resource utilization between treatment arms, nor did it capture costs associated with utilization of the identified healthcare resources. Conclusions: This pre-specified analysis demonstrated that the all-oral triplet regimen of ixazomib added to Rd did not increase healthcare resource utilization compared with placebo-Rd.

Comparative Effectiveness Research on the Treatment Outcomes of Subcutaneous (SC) and Intravenous (IV) Bortezomib (BTZ) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts)

20 Background: AETHERA (NCT01100502) is a randomized Phase 3 study of BV and best supportive care (BSC) vs placebo (PBO) and BSC in the treatment of pts at risk of residual HL post-ASCT. BV consolidation therapy post-ASCT significantly improved progression-free survival (PFS) by independent review vs PBO (HR = 0.57, P = 0.001) and was FDA approved. Most common grade ≥ 3 adverse events were neutropenia (29% BV vs 10% PBO) and peripheral sensory neuropathy (10% vs 1%). The aim of this study was to determine the NNT with BV to avoid 1 additional event, disease progression/death.nnnMETHODSnThe NNT with BV was calculated as the inverse of the absolute risk reduction (ARR); ARR was the PFS event rate per investigator (INV) assessment in the PBO arm minus the event rate in the BV arm of the AETHERA trial. The AETHERA trial recruited pts ≥ 18 yrs at risk of residual HL post-ASCT defined by ≥ 1 of: history of refractory HL; relapse/progression < 12 months after frontline therapy; extranodal involvement at time of pre-ASCT relapse. Pts were randomized to receive BV 1.8 mg/kg or PBO on day 1 of each 21-day cycle, for up to 16 cycles/disease progression.nnnRESULTSn329 pts (median age 32 yrs [range 18-76]; 53% male) received BV (n = 165) or PBO (n = 164). Fewer PFS events per INV analysis were experienced by pts in the BV arm vs PBO arm. The NNT with BV to prevent a disease progression/death ranged from 4.08 (95% CI 2.94, 6.96) to 7.79 pts (95% CI 5.05, 16.4) over 48 months (Table). At 24 months (time majority of pts have progressed post-ASCT), the NNT to prevent a disease progression/death was 4.92 pts (95% CI 3.29, 10.39).nnnCONCLUSIONSnAETHERA data suggest that, at various time points, 1 in every 5-8 pts treated with BV consolidation therapy will benefit by avoiding disease progression/death. This further demonstrates BVs clinical benefit in the post-ASCT consolidation setting.nnnCLINICAL TRIAL INFORMATIONnNCT01100502. [Table: see text].