Hodgkin’s Disease Refractory

While Hodgkin lymphoma has a high cure rate with initial treatment, a significant portion of patients face the challenge of disease that either doesn’t respond to treatment or returns after remission, requiring specialized approaches to achieve successful outcomes.

Table of contents

• What is Relapsed and Refractory Hodgkin Lymphoma
• When Relapse Typically Occurs
• Treatment Options for Relapsed and Refractory Disease
• Chemotherapy Regimens
• Stem Cell Transplantation
• Targeted Therapy
• Radiation Therapy
• Treatments Under Investigation

What is Relapsed and Refractory Hodgkin Lymphoma

The term relapsed refers to disease that reappears or grows again after a period of remission. A remission is when the disease is no longer present or detectable in the body. The term refractory is used to describe when the lymphoma does not respond to treatment, meaning that the cancer cells continue to grow, or when the response to treatment does not last very long.^[1]

Although Hodgkin lymphoma is largely curable with first-line therapy, approximately one-third of patients will not have a complete response to initial treatment or will subsequently relapse. Only 50% of these patients will be effectively managed with conventional therapies. The prognosis is particularly poor for those patients with chemotherapy refractory disease, who are unable to obtain even transient disease control, and for patients who relapse following high dose chemotherapy and autologous stem cell transplant.^[3]

Despite these challenges, for patients who relapse or become refractory, secondary therapies are often successful in providing another remission and may even cure the disease.^[1]

When Relapse Typically Occurs

For classical Hodgkin lymphoma, most relapses typically occur within the first three years following diagnosis, although some relapses occur much later.^[1] This timing is important because it helps doctors determine the best treatment approach for each patient.

Treatment Options for Relapsed and Refractory Disease

A number of treatment options are available for patients with relapsed or refractory Hodgkin lymphoma. The type of treatment prescribed for individual patients depends on several factors, including the timing of the relapse, age and overall health of the patient, scope of disease, and previous therapies received.^[1]

The treatments offered will also depend on where the Hodgkin lymphoma is in the body, how long since it was first treated, and what treatments were used initially.^[2]

The current standard secondary treatment for the majority of patients consists of combination therapy, usually followed by autologous stem cell transplantation, in which a patient’s own stem cells are used. Involved site radiation therapy may also be used.^[1]

Chemotherapy Regimens

Chemotherapy uses anticancer drugs to destroy cancer cells. It may be used to treat Hodgkin lymphoma that comes back after treatment. Chemotherapy may also be used in preparation for a stem cell transplant.^[2]

You may be given the same combination of chemotherapy drugs that was originally used to treat the Hodgkin lymphoma if it responded well to them the first time they were given. You may also be offered a different combination of chemotherapy drugs.^[2]

There are a variety of single-agent and combination therapy regimens that may be used for relapsed or refractory Hodgkin lymphoma, including:^[1]

• Brentuximab vedotin (Adcetris)
• Bendamustine (Treanda)
• Nivolumab (Opdivo)
• Pembrolizumab (Keytruda)
• DHAP (dexamethasone, cisplatin, and cytarabine)
• ESHAP (etoposide, methylprednisolone, cisplatin, and cytarabine)
• GVD (gemcitabine, vinorelbine, and liposomal doxorubicin)
• ICE (ifosfamide, carboplatin, and etoposide)
• IGEV (ifosfamide, gemcitabine, and vinorelbine)

Additional combinations of chemotherapy drugs that may be used include:^[2]

• GDP (gemcitabine, dexamethasone and cisplatin)
• DICEP (dexamethasone, cyclophosphamide, etoposide, cisplatin and mesna)
• GDCRBP (gemcitabine, dexamethasone and carboplatin)
• COPP (cyclophosphamide, vincristine, procarbazine and prednisone)
• CEP (lomustine, etoposide, prednisone and chlorambucil)

Stem Cell Transplantation

Hodgkin lymphoma patients who fail to achieve complete remission following initial therapy or who relapse after achieving complete remission are often treated with second-line chemotherapy regimens, followed by a bone marrow or stem cell transplant. A transplant of bone marrow or stem cells is needed to restore healthy bone marrow.^[1]

A stem cell transplant is the main treatment used for Hodgkin lymphoma that doesn’t completely go away after treatment with chemotherapy or radiation therapy. It may also be offered if the Hodgkin lymphoma comes back soon after the original treatment is finished.^[2]

A stem cell transplant uses high-dose chemotherapy to kill all of the cells in the bone marrow. Healthy stem cells are given to replace the ones in the bone marrow that were destroyed.^[2]

In an autologous type of transplant, the stem cells are taken from your own bone marrow or blood. In an allogeneic type of transplant, stem cells are collected from another person. If the Hodgkin lymphoma remains after an autologous stem cell transplant, an allogeneic stem cell transplant may be an option for some people.^[2]

Targeted Therapy

Targeted therapy uses drugs to target specific molecules, such as proteins, on cancer cells or inside them to stop the growth and spread of cancer and limit harm to normal cells. You may be offered targeted therapy for relapsed or refractory classical Hodgkin lymphoma.^[2]

Radiation Therapy

You may be offered radiation therapy to treat Hodgkin lymphoma that comes back or remains in only one lymph node area if you haven’t already received radiation therapy. Radiation therapy uses high-energy rays or particles to destroy cancer cells. It may be given alone or with chemotherapy. Radiation therapy may also be used in preparation for a stem cell transplant.^[2]

Treatments Under Investigation

Although the cure rate in Hodgkin lymphoma is already high, research continues to look for ways to treat the minority of patients who are refractory to treatment and those who relapse. Many promising therapies are currently under investigation in clinical trials for Hodgkin lymphoma, including:^[1]

• Anti-CD30-CAR T cells
• Atezolizumab (Tecentriq)
• Bortezomib (Velcade)
• Carfilzomib (Kyprolis)
• Everolimus (Afinitor)

The treatment landscape of relapsed or refractory classic Hodgkin lymphoma has evolved significantly over the past decade following the approval of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation, post-transplant maintenance, and treatment of relapse after transplantation, which have led to improved survival in the modern era.^[10]