HSR19-107: Nivolumab for Newly Diagnosed Classical Hodgkin Lymphoma: Patient-Reported Outcomes From CheckMate 205 Cohort D

Background: Patients (pts) with classical Hodgkin lymphoma (cHL) frequently experience reduced health-related quality of life (HRQoL) (Oerlemans et al, Ann Hematol 2011). Nivolumab, a fully human IgG4 anti-programmed death-1 (PD-1) immune checkpoint inhibitor monoclonal antibody, demonstrated efficacy and clinically meaningful improvement in pt-reported outcomes (PROs) in pts with relapsed/refractory cHL in cohorts A, B, and C of CheckMate 205 (NCT02181738) (Armand et al, J Clin Oncol 2018; Engert et al, ASH 2017). Nivolumab monotherapy followed by nivolumab + doxorubicin, vinblastine and dacarbazine (N-AVD) demonstrated an objective response rate of 84% in newly diagnosed cHL (cohort D of CheckMate 205; Ramchandren et al, EHA 2018). We present PROs in CheckMate 205 cohort D. Methods: Pts ≥18 years of age with untreated, advanced-stage cHL, with ECOG performance status (PS) of 0–1 received 4 doses of nivolumab monotherapy (240 mg IV Q2W) followed by N-AVD for 6 cycles (12 doses). Pts then entered the follow-up (FU) period. PROs were an exploratory endpoint, assessed using the EuroQol 5 Dimensions-3 level (EQ-5D-3L) and associated visual analog scale (EQ-VAS) in all treated pts who had both a baseline (monotherapy cycle 1) and post-baseline assessment. EQ-VAS ranges from 0–100, with higher scores indicating better HRQoL. In EQ-5D-3L, pts can report no, some, or extreme problems in each of 5 dimensions (mobility, self-care, activity, pain, and anxiety). Results: 51 pts were treated. At baseline, median age was 37 years, 63% were male, 59% had ECOG PS of 0. 49 pts (96%) completed baseline EQ-VAS. Mean EQ-VAS scores exceeded the mean baseline score at the end of monotherapy, after 2 combination cycles, at the end of therapy, and during follow-up (Table 1). The proportion of pts reporting some or extreme problems in EQ-5D-3L was numerically lower than or similar to baseline after monotherapy for all dimensions, but was numerically higher than baseline (dimensions of mobility and activity) after 2 combination cycles, and remained close to or numerically below baseline during follow-up (dimensions of self-care, activity, pain, and anxiety). Conclusions: Pt-reported HRQoL, as assessed by observed mean EQ-VAS scores, did not deteriorate from baseline during treatment with nivolumab followed by N-AVD. Proportions of pts reporting problems in individual EQ-5D-3L dimensions were generally similar to baseline during treatment and follow-up.

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S821 NIVOLUMAB PLUS DOXORUBICIN, VINBLASTINE AND DACARBAZINE FOR NEWLY DIAGNOSED ADVANCED-STAGE CLASSICAL HODGKIN LYMPHOMA: 2-YEAR EXTENDED FOLLOW-UP FROM COHORT D OF THE PHASE 2 CHECKMATE 205 STUDY

HemaSphere ◽

10.1097/01.hs9.0000561564.12955.95 ◽

2019 ◽

Vol 3 (S1) ◽

pp. 363

Author(s):

E. Domingo-Domènech ◽

R. Ramchandren ◽

A. Rueda ◽

M. Trněný ◽

T. Feldman ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Advanced Stage ◽

Phase 2 ◽

Newly Diagnosed ◽

Classical Hodgkin Lymphoma

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Brentuximab vedotin-containing escalated BEACOPP variants for newly diagnosed advanced-stage classical Hodgkin lymphoma: follow-up analysis of a randomized phase II study from the German Hodgkin Study Group

Leukemia ◽

10.1038/s41375-021-01386-z ◽

2021 ◽

Author(s):

Carla Damaschin ◽

Helen Goergen ◽

Stefanie Kreissl ◽

Annette Plütschow ◽

Frank Breywisch ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Phase Ii ◽

Phase Ii Study ◽

Brentuximab Vedotin ◽

Study Group ◽

Advanced Stage ◽

Newly Diagnosed ◽

Classical Hodgkin Lymphoma ◽

Randomized Phase Ii

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NIVOLUMAB PLUS DOXORUBICIN, VINBLASTINE AND DACARBAZINE FOR NEWLY DIAGNOSED ADVANCED-STAGE CLASSICAL HODGKIN LYMPHOMA: CHECKMATE 205 COHORT D 2-YEAR FOLLOW-UP

Hematological Oncology ◽

10.1002/hon.104_2629 ◽

2019 ◽

Vol 37 ◽

pp. 146-147 ◽

Cited By ~ 2

Author(s):

S. Ansell ◽

R. Ramchandren ◽

E. Domingo-Domènech ◽

A. Rueda ◽

M. Trněný ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Advanced Stage ◽

Newly Diagnosed ◽

Classical Hodgkin Lymphoma

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Final Report of a Phase-II Study of Rituximab Plus ABVD for Patients with Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma.: Results of Long Follow up and Comparison to Institutional Historical Data.

Blood ◽

10.1182/blood.v114.22.1680.1680 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1680-1680 ◽

Cited By ~ 5

Author(s):

Amanda R Copeland ◽

Yumei Cao ◽

Michelle Fanale ◽

Luis Fayad ◽

Peter McLaughlin ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Historical Data ◽

Stage Iii ◽

Advanced Stage ◽

Newly Diagnosed ◽

Classical Hodgkin Lymphoma ◽

Bulky Disease ◽

Long Term Follow Up

Abstract Abstract 1680 Poster Board I-706 We previously reported (Wedgwood et al, ASH, 2007) improvement in event free survival (EFS) using Rituximab+ABVD (RABVD) in newly diagnosed patients with advanced stage classical Hodgkin lymphoma (HL) when compared to the previously published historical data from the International Prognostic Score (IPS) project using standard ABVD (Hasenclever et. Al, NEJM, 1998). The purpose of this report is to provide a final update on the EFS with long term follow up of patients who received RABVD. In addition, because of the potential difference in the EFS reported by the IPS project and a single institution results, we provide a new analysis comparing our RABVD data to that of historical data from our institution. After IRB approval, we conducted a retrospective data analysis on patients with advanced HL treated at our center with ABVD from February 1996 to May 2006. Information was collected for the IPS factors: age, stage, gender, hemoglobin, white blood cell count, albumin, and lymphocyte count. 104 consecutive patients who met the eligibility criteria for the RABVD study were identified, and were evaluable for response with at least 2 year follow up. Median age was 35 years old, 48 were female and 56 male. 23 (22%) had stage II disease, 12 of these with bulky disease, 45 (43%) stage III and 36 (35%) with stage IV. 65 (63%) had IPS 0-2 and 39 (37%) had IPS >2. The institutional 5-year EFS for ABVD patients regardless of IPS was 66%. For those with IPS 0-2 the institutional EFS was 71% compared with 74% reported by the IPS project. The institutional 5 year EFS for patients treated with ABVD with IPS >2 was 55%, compared with 55% reported by the IPS project. With a median of 5 year follow up (6-94 months) the projected EFS for RABVD is 87% which is significantly better than institutional results with ABVD (p=0.0036). Improvement in EFS was observed with RABVD in patients with IPS 0-2 (EFS 89% vs. 71%, p=0.0248); and those with IPS >2 (80% vs. 55%; p=0.0532). In conclusion, this long term follow up data confirms the superiority of RABVD to ABVD in patients with advanced stage classical HL in all risk groups. This data serves as the rationale for a multicenter randomized trial comparing ABVD with RABVD in newly diagnosed patients with classical HL with stage III and IV and IPS >2. The study is currently enrolling patients. Disclosures Off Label Use: Rituximab in Hodgkin lymphoma. Younes:Genentech: Honoraria, Research Funding.

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Rituximab + ABVD Improves Event-Free Survival (EFS) in Patients with Classical Hodgkin Lymphoma in All International Prognostic Score (IPS) Groups and in Patients Who Have PET Positive Disease after 2–3 Cycles of Therapy.

Blood ◽

10.1182/blood.v110.11.215.215 ◽

2007 ◽

Vol 110 (11) ◽

pp. 215-215 ◽

Cited By ~ 9

Author(s):

Amanda R. Wedgwood ◽

Michelle A. Fanale ◽

Luis E. Fayad ◽

Peter McLaughlin ◽

Fredrick B. Hagemeister ◽

...

Keyword(s):

Treatment Outcome ◽

B Cells ◽

Hodgkin Lymphoma ◽

Prognostic Score ◽

Newly Diagnosed ◽

Classical Hodgkin Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Abvd Chemotherapy

Abstract The use of rituximab in classical Hodgkin lymphoma (HL) has been proposed to have a therapeutic value by several mechanisms; to The malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) rarely survive outside their microenvironment of reactive B-cells, and therefore we hypothesized that depleting B-cells from HL microenvironment by rituximab may deprive HRS cells from critical survival and resistance factors and therefore improving the efficacy of chemotherapy, Rituximab may have a direct killing effect on HRS cells that express CD20, and recent data from Johns Hopkins Medical Center suggested that HRS stem cells are CD20+ cells. With this background, we evaluated the safety and efficacy the combination of rituximab and ABVD (R-ABVD) chemotherapy in newly diagnosed patients with classical HL. In addition, PET after 2–3 cycles of ABVD has been shown to confer poor prognosis and therefore proposed to guide future therapy. (Hutchings et al, Blood, 2006) reported a negative PET scan after two cycles of ABVD to be a good predictor of outcome with 96% 2-year progression free survival (PFS). Those with PET positive after 2 cycles had a 0% PFS at 2 years. Thus, we examined the effect of RABVD on early PET imaging and determined whether PET status remains predictive of treatment outcome in patients receiving RABVD. To date 70 newly diagnosed pts are enrolled, of whom 65 pts had at least 12 months of follow up and are evaluable for treatment response. Median age 28 years (Range; 18–72 years). Patients had stage II (50%), stage III (31%), stage IV (19%) disease. Using the IPS prognostic score model, 36 patients (55%) had a score of 2 or higher. With a median follow up of 32 months, the estimated event-free survival (EFS) is for the entire group is 85% and overall survival 98%. EFS for patients with IPS 0–1, 2, and >2 are 95%, 76%, and 77%, respectively, suggesting that R-ABVD improved EFS in all IPS scores with the biggest impact seen in patients with IPS > 2. 55 patients had PET after 2–3 cycles and were included in the predictive analysis of PET on treatment outcome. PET became negative in 43 patients (78%) after completing 2–3 cycles of RABVD and positive in the remaining 12 patients (22%). 5-year EFS for those with negative PET was 93% and 75% for those who remained PET positive (p=0.05). We conclude that in patients with classical HL, the addition of 6 weekly doses of rituximab to standard dose and schedule of ABVD chemotherapy is effective in terms of remission rate and remission duration irrespective of IPS category. Our data confirmed prior reports that patients who remain PET positive after 2–3 cycles have worse prognosis when compared to those that achieve PET negativity. However, the outcome for those who remained PET positive after 2–3 cycles of RABVD seems to be significantly better than what has been previously reported when using ABVD alone. A randomized trial comparing ABVD with RABVD is planned to confirm these observations.

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Longitudinal study of patients’ health-related quality of life using EQ-5D-3L in 11 Swedish National Quality Registers

BMJ Open ◽

10.1136/bmjopen-2020-048176 ◽

2022 ◽

Vol 12 (1) ◽

pp. e048176

Author(s):

Fitsum Sebsibe Teni ◽

Ola Rolfson ◽

Nancy Devlin ◽

David Parkin ◽

Emma Nauclér ◽

...

Keyword(s):

General Population ◽

Secondary Outcome ◽

Vas Score ◽

National Quality ◽

Patient Reported ◽

Hand Fracture ◽

Patient Groups ◽

Vas Scores ◽

Eq Vas

ObjectiveTo compare problems reported in the five EQ-5D-3L dimensions and EQ VAS scores at baseline and at 1-year follow-up among different patient groups and specific diagnoses in 11 National Quality Registers (NQRs) and to compare these with the general population.DesignLongitudinal, descriptive study.Participants2 66 241 patients from 11 NQRs and 49 169 participants from the general population were included in the study.Primary and secondary outcome measuresProportions of problems reported in the five EQ-5D-3L dimensions, EQ VAS scores of participants’ own health and proportions of participants and mean/median EQ VAS score in the Paretian Classification of Health Change (PCHC) categories.ResultsIn most of the included registers, and the general population, problems with pain/discomfort were the most frequently reported at baseline and at 1-year follow-up. Mean EQ VAS score (SD) ranged from 45.2 (22.4) among disc hernia patients to 88.1 (15.3) in wrist and hand fracture patients at baseline. They ranged from 48.9 (20.9) in pulmonary fibrosis patients to 83.3 (17.4) in wrist and hand fracture patients at follow-up. The improved category of PCHC, improvement in at least one dimension without deterioration in any other, accounted for the highest proportion in several diagnoses, corresponding with highest improvement in mean EQ VAS score.ConclusionsThe study documented self-reported health of several different patient groups using the EQ-5D-3L in comparing with the general population. This demonstrated the important role of patient-reported outcomes in routine clinical care, to assess and follow-up health status and progress within different groups of patients. The EQ-5D-3L descriptive system and EQ VAS have an important role in providing a ‘common denominator’, allowing comparisons across NQRs and specific diagnoses.Trial registration numberClinicalTrials.gov (NCT04359628).

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Patient-proxy agreement on change in acute stroke patient-reported outcome measures: a prospective study

Journal of Patient-Reported Outcomes ◽

10.1186/s41687-021-00329-7 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Brittany R. Lapin ◽

Nicolas R. Thompson ◽

Andrew Schuster ◽

Irene L. Katzan

Keyword(s):

Physical Function ◽

Inpatient Rehabilitation ◽

Patient Reported Outcome Measures ◽

Meaningful Change ◽

Meaningful Improvement ◽

T Score ◽

Patient Reported ◽

Exact Agreement ◽

Over Time

Abstract Objectives Research has indicated proxies overestimate symptoms on patients’ behalves, however it is unclear whether patients and proxies agree on meaningful change across domains over time. The objective of this study is to assess patient-proxy agreement over time, as well as agreement on identification of meaningful change, across 10 health domains in patients who underwent acute rehabilitation following stroke. Methods Stroke patients were recruited from an ambulatory clinic or inpatient rehabilitation unit, and were included in the study if they were undergoing rehabilitation. At baseline and again after 30 days, patients and their proxies completed PROMIS Global Health and eight domain-specific PROMIS short forms. Reliability of patient-proxy assessments at baseline, follow-up, and the change in T-score was evaluated for each domain using intra-class correlation coefficients (ICC(2,1)). Agreement on meaningful improvement or worsening, defined as 5+ T-score points, was compared using percent exact agreement. Results Forty-one patient-proxy dyads were included in the study. Proxies generally reported worse symptoms and functioning compared to patients at both baseline and follow-up, and reported less change than patients. ICCs for baseline and change were primarily poor to moderate (range: 0.06 (for depression change) to 0.67 (for physical function baseline)), and were better at follow-up (range: 0.42 (for anxiety) to 0.84 (for physical function)). Percent exact agreement between indicating meaningful improvement versus no improvement ranged from 58.5–75.6%. Only a small proportion indicated meaningful worsening. Conclusions Patient-proxy agreement across 10 domains of health was better following completion of rehabilitation compared to baseline or change. Overall change was minimal but the majority of patient-proxy dyads agreed on meaningful change. Our study provides important insight for clinicians and researchers when interpreting change scores over time for questionnaires completed by both patients and proxies.

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