Individuals who fail initial treatment for Hodgkin’s lymphoma (HL) remain curable using high dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), CAR T cells, and precision cancer medicines. The current dilemma is how best to use these therapies?
Patients with relapsed or recurrent HL can be divided into two broad categories. Patients who fail to achieve an initial complete disappearance or remission of their cancer following a complete course of chemotherapy treatment are referred to as “induction failures.” Other patients achieve a complete remission to initial treatment and later experience a cancer recurrence. These patients are said to have relapsed or recurrent HL. Relapse of HL may occur several months to years after the initial remission; however, the majority of relapses occur within 2 years of initial treatment.1
Historically, patients with recurrent HL were treated with additional chemotherapy using drugs to which the patient had not been previously exposed and or radiation therapy. Treatment of relapsed patients with several cycles of “salvage” chemotherapy produces a complete disappearance or remission of cancer in 30%-40% of patients and as many as 20% survive without an additional cancer relapse.1
In the 1990’s it was demonstrated that HDC and ASCT cured more patients with recurrent HL compared to conventional “salvage” chemotherapy and HDC became the standard treatment for the majority of patients with relapsed HL.2,3,4
The basic strategy uses higher doses of chemotherapy, which kills more cancer cells than lower doses. Unfortunately, the higher doses of therapy used to destroy cancer cells also damages normal cells. The body’s normal cells that are most sensitive to destruction by HDC are the blood-producing “stem: cells in the bone marrow. To “rescue” the bone marrow and hasten blood cell production and immune system recovery, HDC is followed by an infusion of autologous stem cells collected from the patient prior to administering the HDC.
Radiation Treatment of Relapsed Hodgkin’s Lymphoma
Radiation therapy can be used with curative or palliative intent for recurrences. If the recurrences are localized and can be encompassed within a tolerable field of radiation, good results can be achieved. More often, patients with recurrent HL receive radiation for palliation of local symptoms.
Strategies to Improve Treatment
The progress that has been made in the treatment of relapsed Hodgkin’s lymphoma has resulted from the development of high-dose chemotherapy regimens, new treatment strategies and their evaluation in clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of Hodgkin’s lymphoma.
CAR T Cells: The use of a patient’s own immune cells to fight cancer through a technique called CART therapy, is proving to be a promising therapeutic approach in the treatment of some lymphomas.
Immunotherapy: Keytruda® is a monoclonal antibody that helps to restore the body’s immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein used by cancer cells called PD-L1, to escape an attack by the immune system. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat and initiate an attack to destroy the cancer. Keytruda® was approved for the treatment of recurrent HL based on data in 210 patients from the KEYNOTE-087 trial, which demonstrated an overall response rate of 69 percent with a complete remission rate of 22 percent and a partial remission rate of 47 percent. The median follow-up time was 9.4 months. Among the 145 responding patients, the median duration of response was 11.1 months.2
New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as treatment is an active area of clinical research carried out in phase II clinical trials in patients with relapsed or recurrent lymphoma.
2 arella C, Cuttica A, Vitolo U, et al.: High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence. Cancer 97 (11): 2748-59, 2003.
3 Schmitz N, Pfistner B, Sextro M, et al.: Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 359 (9323): 2065-71, 2002.
4 Rancea M, Monsef I, von Tresckow B, et al.: High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database Syst Rev 6: CD009411, 2013.