A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent).

Study Overview
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Brief Summary
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The purpose of this open-label, single-arm study was to evaluate the impact of venetoclax on the quality of life of participants including those with with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL; a type of cancer affecting the blood and the bone marrow) with or without the 17p deletion or TP53 mutation, including participants with an unknown status, as well as R/R CLL participants who had been previously treated with B-cell receptor inhibitor (BCRi) therapy. The starting dose of venetoclax was 20 mg once daily. The dose must have been gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Participants may have continued receiving venetoclax for up to 2 years. After the treatment period, participants may have continued on into a 2-year follow-up period.

Official Title
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Open-Label, Single Arm, Phase 3b, Multi-Center Study Evaluating the Impact of Venetoclax on the Quality of Life of Relapsed/Refractory Subjects With Chronic Lymphocytic Leukemia (CLL) (VENICE II)

Conditions
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Chronic Lymphocytic Leukemia (CLL)

Intervention / Treatment
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* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2 Participant has relapsed/refractory disease (received at least one prior therapy) Diagnosis of CLL that meets published 2008 Modified International Workshop on CLL National Cancer Institute - Working Group (IWCLL NCI-WG) Guidelines and: has an indication for treatment according to the 2008 Modified IWCLL NCI-WG Guidelines has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam) with or without 17p deletion or TP53 mutation may have been previously treated with a prior B-cell receptor inhibitor therapy Adequate bone marrow function Exclusion Criteria: Participant has developed Richter's transformation or Prolymphocytic leukemia (PLL) Participant has previously received venetoclax History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of: adequately treated in situ carcinoma of the cervix uteri adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin previous malignancy confined and surgically resected (or treated with other modalities) with curative intent Active and uncontrolled autoimmune cytopenias (within 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), despite low dose corticosteroids Prior allogeneic stem cell transplant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venetoclax<br>Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 weeks. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. | Drug: Venetoclax<br>* Venetoclax tablets were to be taken orally once daily with a meal and water in the morning at approximately the same time each day. Tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.<br>* Other names: VENCLYXTO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Week 48 in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Physical Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Role Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a role functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the role functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Emotional Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an emotional functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the emotional functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Cognitive Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a cognitive functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the cognitive functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Social Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a social functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the social functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a fatigue scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the fatigue scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Nausea and Vomiting Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a nausea and vomiting scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the nausea and vomiting scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Pain Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a pain scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the pain scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Dyspnea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a dyspnea scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the dyspnea scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Insomnia Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an insomnia scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the insomnia scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Appetite Loss Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an appetite loss scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the appetite loss scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Constipation Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a constipation scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the constipation scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Diarrhea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a diarrhea scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the diarrhea scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Financial Difficulties Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a financial difficulties scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the financial difficulties scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the fatigue scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Treatment Side Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the treatment side effects scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Disease Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the disease effects scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Infection Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the infection scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Social Problems Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the social problems scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in Future Health Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the future health scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale Score | The EQ-5D 5L measures quality of life in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems), and a separate visual analog scale (VAS). Participants rated their health on a vertical visual analogue scale, where the endpoints were labelled 100, The best health you can imagine and 0, The worst health you can imagine. Positive values indicate improvement from baseline. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Health Index Score | The EQ-5D 5L measures quality of life in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems), and a separate visual analog scale (VAS). The scores for the 5 dimensions are used to compute a single utility index score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual, with '0' defined as a health state equivalent to being dead and '1' is full health. The higher the score the better the health status. Positive values indicate improvement from baseline. | Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108) | 
| Complete Remission Rate (Complete Remission [CR] + Complete Remission With Incomplete Marrow Recovery [CRi]) | Complete remission rate (CR + CRi) is defined as the percentage of participants achieving a CR or CRi as their best response (per the investigator assessment) based on 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria. | From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks | 
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria as assessed by investigator using the best response at any time during the study. | From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks | 
| Duration of Overall Response (DOR) | DoR is defined as the number of days from the date of first response (complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria to the earliest date of progressive disease (PD) or death. DOR was analyzed by Kaplan-Meier (K-M) methodology. | From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks | 
| Time to Progression (TTP) | TTP is defined as the number of days from the date of first dose of venetoclax to the date of earliest disease progression (PD). TTP was analyzed by Kaplan-Meier (K-M) methodology. | From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks | 
| Progression-Free Survival (PFS) | PFS is defined as the number of days from the date of first dose of venetoclax to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology. | From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks | 
| Overall Survival (OS) | OS is defined as the number of days from the date of first dose of venetoclax to the date of death. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology. | From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed CLL, Refractory CLL, 17p deletion, TP53 gene, B-Cell receptor inhibitor (BCRi), European Organization of Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), Overall response rate (ORR), Duration of overall response (DOR), Complete remission rate (CR + CRi), Progression-free survival (PFS), Overall survival (OS)