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Lymphoma

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Hodgkin Lymphoma

Participants diagnosed with high-risk stage IIb-IV cHL, received frontline treatment with chemotherapy with or without radiotherapy between 01 January 2010 and 31 December 2013 from the 13 participating countries will be observed for various treatments received for cHL, associated adverse events and resources used from the date of cHL diagnosis until the date of first documented relapse or disease progression after frontline therapy. Participants will be continue to be observed for overall survival until the date of death or data collection, whichever occurs first.

Participants diagnosed with RRHL, between 01 January 2010 and 31 December 2013 from the 13 participating countries will be observed for various treatments received for RRHL, detailed data on treatment pathways, clinical outcomes, associated adverse events and resources used from the date of RRHL diagnosis until the date death or data collection, whichever occurs first. Participants will be continue to be observed for overall survival until the date of death or data collection, whichever occurs first.

Medical Director

The purpose of this study is to describe progression-free survival (PFS) in participants with relapsed or refractory classical Hodgkin lymphoma (RRHL), defined as the time from initiation of first treatment for RRHL to first documentation of relapse or disease progression, or death.

This is a retrospective, non-interventional study of participants with newly-diagnosed cHL, or with RRHL. The study will review the medical records of participants to describe participant's demographics, disease characteristics, treatments received, outcomes, health resources used by the participants, and adverse events that are associated with treatments, and resources used for treatment.

The study will enroll approximately 50 to 100 participants in each group at each of the 13 participating countries. Based on the diagnosis of the disease, participants will be assigned to one of the following groups:

Group 1: cHL Group 2: RRHL

This multi-center trial will be conducted in Argentina, Australia, China, Colombia, Hong Kong, Mexico, Republic of Korea, Russia, Saudi Arabia, Singapore, South Africa, Taiwan, and Turkey. The data for Group 1 and Group 2 will be collected from date of cHL or RRHL diagnosis until the date of death (or the date when the participant was last known to be alive, whichever occurs first).

B-CD30 + Hodgkin Lymphoma International Multi-center Retrospective Study of Treatment Practices and Outcomes

An International, Multi-centre, Non-interventional Retrospective Study to Describe Treatment Pathways, Outcomes, and Resource Use in Patients With Classical Hodgkin Lymphoma (B-HOLISTIC)

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

PFS was defined as time from initiation of frontline regimen to first documentation of relapse or disease progression or death, censored at date of most recent follow-up/contact. Progressive disease (PD) was defined as any new lesion or increase by \>=50% of previously involved site from nadir, and was evaluated based on International Working Group (IWG) criteria (Cheson et al 2007). Median PFS was estimated using the Kaplan-Meier method.

The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (lessspread) to IV (more spread). Additional sub staging variables include: A, asymptomatic; and B, presence of B symptoms (including fever, night sweats and weight loss of \>=10 percent \[%\] of body weight over 6 months).

The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (lessspread) to IV (more spread). Additional sub staging variables include: A, asymptomatic; and B, presence of B symptoms (including fever, night sweats and weight loss of \>=10 % of body weight over 6 months).

The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). Additional sub staging variables include: A, asymptomatic; and B, presence of B symptoms (including fever, night sweats and weight loss of \>=10% of body weight over 6 months).

IPS score was calculated based on following factors: age \>=45 years, male sex, stage IV disease, albumin\<4 gram per liter (g/L), white blood cell (WBC)\>=15\*10\^9 per liter (/L), haemoglobin \<10.5 g/L, and lymphocyte count\<0.6\*10\^6/L or \<8% of differential. One point was assigned for each of above factors. The sum of points allotted correlates with following risk groups: good risk (0-1 points)-5 year survival of 89-90%; fair risk (2 to 3 points)-5 year survival of 78-81%; poor risk (4-7 points)-5 year survival of 56-61%. Total score range is 0 to 7, lower scores indicate higher survival rate.

The Ann Arbor staging system of lymphomas is used to summarize the extent of the cancer's spread. Stages are classified by Roman numerals I (less spread) to IV (more spread). If the following symptoms (B-symptoms) are present, a "B" classification is added to the stage: fever, night sweats and weight loss of \>=10% of body weight over 6 months. B-symptoms indicate the presence of systemic symptoms. The presence or absence of B-symptoms has prognostic significance and is reflected in the staging of these lymphomas.

Number of participants were categorized based on prior therapies for HL at each line of treatment.

Therapy regimens were numbered as 1: Doxorubicin (Doxo) + Bleomycin (bleo) + Vinblastine (Vinbl) + Decarbazine (Dacar) (ABVD); 3: Doxo + Vinbl + Mechlorethamine + Etoposide (Eto) + Vincristilne (Vinc) + Bleo + Prednisone (Pred) (Stanford V); 6: Cyclophophamide (Cyclo) + Vinc + Procarbazine (Procarb) + Pred (C-MOPP); 7: Dexamethasone + Cytarabine + Cisplatin (DHAP); 8: Eto + Methylprednisolone + Cytarabine + Cisplatin (ESHAP); 10: Ifosfamide+ Carboplatin + Eto (ICE); 11: Ifosfamide + Gemcitabine +Vinorelbine + Pred (IGEV); 17: Rituximab; 18: Brentuximab vedotin; 4: Bleo + Eto + Doxo + Cyclo + Vinc + Procarb + Pred (BEACOPP); 14: Cycl + Doxo + Vinc + Pred (CHOP); 15: Cycl + Vinc + Pred (CVP); 2: ABVD + Doxo + Bleo + Vinbl + Dacar then Bleo + Eto + Doxo + Cycl + Vinc + Procarb+ Pred ( Escalated BEACOPP); 24: Other.

Therapy regimens were numbered as 1: ABVD; 3: Stanford V; 6: C-MOPP; 7: DHAP; 8: ESHAP; 10: ICE; 11: IGEV; 17: Rituximab; 18: Brentuximab vedotin; 4: BEACOPP; 14: CHOP; 15: CVP; 2: ABVD + Escalated BEACOPP; 24: Other.

Therapy regimens were numbered as 1: ABVD; 6: C-MOPP; 7: DHAP; 8: ESHAP; 10: ICE; 11: IGEV; 12: Carmustine + Cytarabine + Etoposide + Melphalan (Mini-BEAM); 13: Etoposide + Ifosfamide + Mesna + Mitoxantrone (MINE); 18: Brentuximab vedotin; 16: Gemcitabine + Vinoreilbine + Pegylated liposomal doxorubicin (GVD); 4: BEACOPP; 14: CHOP; 24: Other.

Assessment was done for RT's whether used for pre-planned frontline treatment or for residual Fluorodeoxyglucose (FDG)-avid disease.

Therapy regimens were numbered as 1: ABVD; 6: C-MOPP; 8: ESHAP; 11: IGEV; 12: Mini-BEAM; 18: Brentuximab vedotin; 22: Nivolumab; 24: Other.

Reasons for ASCT-eligible participants for not undergoing ASCT included participant refusal, inability to mobilize stem cells, loss of response to chemotherapy, cumulative toxicities, comorbid conditions, others, and unknown.

Reasons for ASCT ineligibility included advanced age, comorbid conditions, chemoresistant disease, cumulative toxicities, and others.

Therapy regimens were numbered as 1: ABVD; 2: ABVD followed by Escalated BEACOPP; 3: Stanford V; 4: BEACOPP; 6: Cyclophosphamide C-MOPP; 7: DHAP; 8: ESHAP; 9: GCD; 10: ICE; 11: IGEV; 12: Mini-BEAM; 13: MINE; 14: CHOP; 15: CVP; 16: GVD; 17: Rituximab; 18: Brentuximab vedotin; 19: Bendamustine; 22: Nivolumab; 23: Pembrolizumab; 24: Other. More than one line of treatment or therapy was selected for each participant.

Therapy regimens were numbered as 1: ABVD; 3: Stanford V; 6: C-MOPP; 7: DHAP; 11: IGEV; 19: Bendamustine; 4: BEACOPP; 13: MINE; 14: CHOP; 24: Other; 8: ESHAP; 9: Gemcitabine + Carboplatin + Dexamethasone (GCD); 10: ICE; 17: Rituximab; 18: Brentuximab vedotin; 15: CVP; 2: ABVD followed by Escalated BEACOPP; 22: Nivolumab; 16: GVD; 21: Lenalidomide; 24: Other.

Therapy regimens were numbered as 1: ABVD; 3: Stanford V; 6: C-MOPP; 7: DHAP; 11: IGEV; 4: BEACOPP; 14: CHOP; 15: CVP; 2: ABVD followed by Escalated BEACOPP; 24: Other; 8: ESHAP; 9: GCD; 10: ICE; 13: MINE; 17: Rituximab; 18: Brentuximab vedotin; 19: Bendamustine; 22: Nivolumab. More than one line of treatment or therapy was selected for each participant

Therapy regimens were numbered as 8: ESHAP; 10: ICE; 11: IGEV; 12: Mini-BEAM; 18: Brentuximab vedotin; 19: Bendamustine; 16: GVD; 24: Other. Conditioning regimens are BEAM (Carmustine + Etoposide + Cytarabine + Melphalan), CBV (cyclophosphamide + Carmustine + vp16) BeEAM (bendamustine) and Gemcitabine/Busulfan/Melphalan.

Known risk factors for relapse after ASCT included time to first relapse less than or equal to (\<=) 3 months, stage IV disease at relapse, bulky disease \>=5 centimeter (cm) at relapse, extranodal disease, inadequate response to salvage chemotherapy (partial remission \[PR\] or PET positivity), performance status (eastern Cooperative oncology group \[ECOG\]) \>=1. The ECOG assessment used a 3-point scale, including scores of 0 (fully active/able to carry on all pre-disease activities without restriction), 1 (restricted in physically strenuous activity but ambulatory/able to carry out light or sedentary work), or 2 (ambulatory for more than 50% of waking hours and capable of all self care but unable to carry out any work activities).

Therapy regimens were numbered as 1: ABVD; 6: C-MOPP; 7: DHAP; 8: ESHAP; 9: GCD; 10: ICE; 11: IGEV; 12: Mini-BEAM; 13: Eto + Ifosfamide + Mesna + Mitoxantrone (MINE); 18: Brentuximab vedotin; 19: Bendamustine; 22: Nivolumab; 16: GVD; 4: BEACOPP; 14: CHOP; 2: ABVD + Escalated BEACOPP; 24: Other.

Therapy regimens were numbered as 1: ABVD; 7: DHAP; 10: ICE; 11: IGEV; 4: BEACOPP; 2: ABVD followed by Escalated BEACOPP; 8: ESHAP; 12: Mini-BEAM; 13: MINE; 18: Brentuximab vedotin; 22: Nivolumab; 23: Pembrolizumab; 16: GVD, 9: GCD; 24: other; 19: Bendamustine; 14: CHOP; 17: Rituximab.

Therapy regimens were numbered as 9: GVD; 10: ICE; 11: IGEV; 12: Mini-BEAM; 18: Brentuximab vedotin; 19: Bendamustine; 22: Nivolumab.

Therapy regimens were numbered as 1: ABVD; 7: DHAP; 10: ICE; 11: IGEV; 4: BEACOPP; 2: ABVD followed by Escalated BEACOPP; 8: ESHAP; 12: Mini-BEAM; 13: MINE; 18: Brentuximab vedotin; 9: GCD; 22: Nivolumab; 23: Pembrolizumab; 16: GVD.

Data for PET-CT scan and CT scans were assessed for baseline, frontline and relapse/or refractory, and radiotherapy was assessed for frontline and relapse/refractory, as planned.

Data for PET-CT scan and CT scans were assessed for baseline, frontline and relapse or refractory, as planned.

PFS was defined as time from initiation of frontline regimen to first documentation of relapse or disease progression or death, censored at date of most recent follow-up/contact. PD was defined as any new lesion or increase by \>= 50% of previously involved site from nadir, and was evaluated based on IWG criteria (Cheson et al 2007). Median PFS was estimated using the Kaplan-Meier method.

Best clinical response as complete remission (CR), partial remission (PR), stable disease (SD), or PD was evaluated based on IWG criteria (Cheson et al 2007). CR was the disappearance of all evidence of disease. PR was the regression of measurable disease and no new sites. SD was defined by failure to achieve CR, PR, or PD. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir.

Best clinical response as CR, PR, SD, or PD was evaluated based on IWG criteria (Cheson et al 2007). CR was the disappearance of all evidence of disease. PR was the regression of measurable disease and no new sites. SD was defined by failure to achieve CR, PR, or PD. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir.

Duration of best response was defined as the time from when the criteria for response (CR or PR) were met to first documentation of relapse or disease progression, and was evaluated based on IWG criteria (Cheson et al 2007). CR was the disappearance of all evidence of disease. PR was the regression of measurable disease and no new sites. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir.

Median OS was defined as the time from diagnosis of cHL to death(Group 1)/ time from first relapse after frontline therapy to death (Group 2), censored at date of most recent follow-up/contact.

Percentage of participants who were alive at 1 and 5 years after diagnosis in cHL participants are reported. 5 year overall survival data were reported only for participants who had \>5 year observation periods.

Percentage of participants who were alive at 1 and 5 years after diagnosis in RRHL participants are reported. 5 year overall survival data were reported only for participants who had \>5 year observation periods.

Length of stay by unit or ward included general, high dependency/intermediate, intensive care unit, bone marrow transplant unit, and emergency visits.

Each participant had more than one category presented for salvage therapy and ASCT.

Length of stay by unit or ward included general, high dependency/intermediate, intensive care unit, bone marrow transplant unit, and emergency visits. Each participant had more than one category presented for salvage therapy and ASCT.

Each participant had more than one category presented for salvage therapy and ASCT. Scan procedures included chest x-ray, magnetic resonance imaging, needle biopsy, bone scan, bone marrow aspiration, flow cytometry, and other scan procedures.

Takeda

At each visit the investigator had to assess any occurrence of adverse events. Participants may report adverse events occurring at any other time during the study. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Participants diagnosed with high-risk stage IIb-IV cHL between 01 January 2010 and 31 December 2013, who received frontline treatment with chemotherapy with or without radiotherapy, and participants who were diagnosed with high-risk stage IIb-IV cHL and then were subsequently diagnosed with RRHL between 2010 and 2013 were observed retrospectively until the date of death or data collection, whichever occurred first.

Group 1: cHL

Participants diagnosed with RRHL between 01 January 2010 and 31 December 2013, and participants who were diagnosed with high-risk stage IIb-IV cHL and then were subsequently diagnosed with RRHL between 2010 and 2013 were observed retrospectively until the date of death or data collection, whichever occurred first.

Group 2: RRHL

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

The full analysis set (FAS) included all participants who were eligible for cHL or RRHL group including the common participants in both the groups.

The FAS included all participants who were eligible for RRHL group including the common participants in both the groups.

Group 2, RRHL: Progression Free Survival (PFS)

The FAS included all participants who were eligible for cHL group including the common participants in both the groups.

Group 1, cHL: Number of Participants Based on Clinical Staging According to Ann Arbor Staging at Diagnosis

Group 2, RRHL: Number of Participants Based on Clinical Staging According to Ann Arbor Staging at Diagnosis

Clinical stage at 2nd relapse

Clinical stage at 3rd relapse

Clinical stage at 4th relapse

Clinical stage at 5th relapse

The FAS included all participants who were eligible for RRHL group including the common participants in both the groups. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure.

Group 2, RRHL: Number of Participants Based on Clinical Staging According to Ann Arbor Staging at Relapse After First Relapse or Refractory Diagnosis

The FAS included all participants who were eligible for cHL group including the common participants in both the groups. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure.

Group 1, cHL: Number of Participants Based on Each International Prognostic Score (IPS) Category

Group 1, cHL: Number of Participants With B Symptoms at Diagnosis

Group 2, RRHL: Number of Participants With B Symptoms at Diagnosis

Frontline treatment

Second line treatment

Third line treatment

Pre-SCT line treatment

Group 2, RRHL: Number of Participants Categorized Based on Prior Therapies for Hodgkin Lymphoma (HL) at Each Line of Treatment

Group 2, RRHL: Median Number of Previous Treatment Regimens (Chemotherapies) Received

Therapy regimen 1

Therapy regimen 3

Therapy regimen 6

Therapy regimen 7

Therapy regimen 8

Therapy regimen 10

Therapy regimen 11

Therapy regimen 17

Therapy regimen 18

Therapy regimen 4

Therapy regimen 14

Therapy regimen 15

Therapy regimen 2

Therapy regimen 24

Group 1, cHL: Number of Participants Categorized Based on Frontline Treatment Regimens

The FAS included all participants who were eligible for cHL group including the common participants in both the groups. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given categories.

Group 1, cHL: Median Number of Treatment Cycles Associated With Each Frontline Treatment Regimen

Therapy regimen 12

Therapy regimen 13

Therapy regimen 16

Group 1, cHL: Number of Participants Who Received Treatments for HL After Completion of Frontline Therapy (Before Relapse)

RT Type: Whole body

RT Type: Involved-field

RT Type: Involved-site

RT Type: Involved-node

RT Type: Other

RT Site: Abdominal nodes

RT Site: Axillary nodes

RT Site: Bone lesions

RT Site: Breast

RT Site: Cervix

RT Site: Inguinal nodes

RT Site: Larynx

RT Site: Lung

RT Site: Mediastinal nodes

RT Site: Neck nodes

RT Site: Pancreas

RT Site: Para-aortic nodes

RT Site: Para-iliac nodes

RT Site: Pelvic nodes

RT Site: Skin

RT Site: Soft tissue

RT Site: Spleen

RT Site: Supraclavicular nodes

RT Site: Thyroid

RT Site: Other

Group 1, cHL: Number of Participants Based on Radiotherapy (RT) Type and Site When Received at Frontline

RT for pre-planned frontline treatment

RT for residual FDG-avid disease

Group 1, cHL: Number of Participants Categorized Based on RT Treatment Given as Pre-planned Frontline Treatment and RT Treatment Given for Residual Fluorodeoxyglucose (FDG)-Avid Disease

Eligible for ASCT

Ineligible for ASCT

Initially ineligible and became eligible for ASCT

Became eligible and received ASCT

Eligible and received ASCT

Eligible and did not receive ASCT

The FAS included all participants who were eligible for RRHL group including the common participants in both the groups. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given categories.

Group 2, RRHL: Percentage of Participants Categorized Based on ASCT Eligibility Assessment

Therapy regimen 22

The FAS included all participants who were eligible for RRHL group including the common participants in both the groups. . Here "overall number of participants" analyzed are those who were evaluable for this outcome measure. Here number analyzed "n" are the participants who were evaluable for the outcome measure at given categories.

Group 2, RRHL: Median Number of Treatment Cycles Associated With Relapse/ Refractory Treatment Regimen for ASCT

Participant refusal

Inability to mobilize stem cells

Loss of response to chemotherapy

Cumulative Toxicities

Other

Comorbid conditions

Unknown

The FAS included all participants who were eligible for RRHL group including common participants. Here "overall number of participants" analyzed are those who were evaluable for this outcome measure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
B-CD30 + Hodgkin Lymphoma International Multi-center Retrospective Study of Treatment Practices and Outcomes	NCT03327571	Classical Hodgk... Relapsed or Ref...		18 Years -	Takeda
B-CD30 + Hodgkin Lymphoma International Multi-center Retrospective Study of Treatment Practices and Outcomes	NCT03327571	Classical Hodgk... Relapsed or Ref...		18 Years -	Takeda

Spots Global Cancer Trial Database for relapsed or refractory classical hodgkin lymphoma