Anti-PD-1 and Chemotherapy for R/R Hodgkin Lymphoma

Efficacy of Chemotherapy or Chemo-anti-PD-1 Combination After Failed Anti-PD-1 Therapy for Relapsed and Refractory Hodgkin Lymphoma: a Series From Lysa Centers.

Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known.

In this context, the optimal treatment for patients who failed after anti-PD-1 therapy is an issue. To better assess their outcome, the investigators retrospectively analyzed the characteristics and outcome of patients from 14 LYSA (The Lymphoma Study Association) centers who lost response to anti-PD-1 therapy and received additional CT.

Study Overview

• Status: Completed
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Biological: Evaluate the improvement in response from the end of anti-PD-1 monotherapy

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• France
  • Pierre-Bénite, France
    • Centre Hospitalier Lyon Sud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The initial diagnosis of classical HL was established from biopsies in accordance with the 2008 World Health Organization classification14. We retrospectively analyzed 30 R/R classical HL patients from 14 LYSA centers who received anti-PD-1 therapy as part of a clinical trial (n=4), from an off-label program authorization for temporary use (ATU) from the French medical drug agency (Agence Nationale de Sécurité du Médicament, ANSM) (n=22), from the Belgian national system for the reimbursement of health care (Institut National d'Assurance Maladie Invalidité, INAMI) (n=4).

Description

Inclusion Criteria:

• Initial diagnosis of classical HL
• Optional histopathology confirmation of relapse/refractory HL, (2) age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status from 0 to 2
• Patients must be have received: at least 2 prior regimens and have received or be ineligible for autologous stem cell transplant and must have received prior BV, and at least 2 cycles of single agent anti-PD-1 as last treatment before entering the study,
• Patients must have inadequate response to anti-PD-1 monotherapy (progressive disease or partial response according to Lugano criteria) with at least one hypermetabolic lesion over the liver and mediastinum background at time of inclusion in the study
• Previous allogeneic stem cell transplant was allowed. Patients treated with radiotherapy alone after anti-PD1 or combined with anti-PD1 treatment were not included in the study.

Exclusion Criteria:

- radiotherapy in the treatment after anti-PD1

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1 Sequential strategy; Patients for whom anti-PD-1 therapy was stopped with the introduction of a new treatment line (19 patients, 63%).	Biological: Evaluate the improvement in response from the end of anti-PD-1 monotherapy; Evaluate the improvement in response from the end of anti-PD-1 monotherapy to the first evaluation after introduction of CT alone (Group 1) or combined with anti-PD-1 (Group 2).
Group 2 Concomitant strategy; Patients for whom a combination of CT with anti-PD-1 therapy was initiated (11 patients, 37 %).	Biological: Evaluate the improvement in response from the end of anti-PD-1 monotherapy; Evaluate the improvement in response from the end of anti-PD-1 monotherapy to the first evaluation after introduction of CT alone (Group 1) or combined with anti-PD-1 (Group 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate after re-exposure to chemotherapy	Patient evaluation was timed by treating physicians according to the policy of each center, and all patients were evaluated after a median of 10 weeks (min 7 weeks, max 12 weeks) with PET/CT using Lugano criteria	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best response obtained (Group 1)	the best response obtained with CT after anti-PD-1	10 weeks
Best response obtained (Group 2)	the best response obtained with CT after the combination anti-PD-1 and CT	10 weeks
The toxicities experienced during CT or anti-PD-1 plus CT combination	The toxicities were graded retrospectively according to the National Cancer Institute Common Toxicity Criteria for AEs (version 4.0).	10 weeks
Outcomes including PFS	PFS was defined as the time from first relapse, or progression, to the next event (defined as either second relapse/progression, change of therapy, or death from any cause)	up to 12 months
Outcomes including overall survival (OS).	OS was defined as the time from first relapse, or progression, to death from any cause.	up to 24 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Hervé GHESQUIERES, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): January 31, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: June 4, 2018
• First Submitted That Met QC Criteria: September 7, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: September 7, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: chemotherapy; Immunotherapy; anti-PD1; re-sensibilization
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• Other Study ID Numbers: Anti-PD-1 Hodgkin

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No