by Dr. C.H. Weaver M.D. Medical Editor, updated 5/2019
Patients with relapsed or recurrent Hodgkin’s lymphoma are curable and can be further 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 Hodgkin’s lymphoma. Relapse of cancer may occur several months to years after the initial remission; however, the majority of relapses occur within 2 years of initial treatment.
Treatment of Induction Failures
Patients who fail to achieve an initial complete remission or disappearance of their cancer following a complete course of chemotherapy treatment are referred to as “induction failures.” This is a broad group since it includes patients whose cancer actually grew or progressed during chemotherapy as well as those with an almost complete disappearance of cancer. Historically, all of these patients were treated with additional chemotherapy using drugs to which the patient had not been previously exposed and/or radiation therapy. Treatment of induction failures with several cycles of “salvage” chemotherapy produces a complete remission of cancer in 30%-40% of patients and up to ~20% of patients survive without an additional cancer relapse.
In the 1980’s high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) was discovered to cure 40%-50% of induction failures which was a marked improvement over traditional conventional chemotherapy.
In 1993 a clinical trial confirmed the benefit of HDC and ASCT, reporting in the medical journal Lancet that there HDC and ASCT resulted in a 53% chance of being alive without disease recurrence, compared to only 10% for patients treated with conventional chemotherapy. HDC and ASCT has become the standard initial salvage treatment for the majority of patients with Hodgkin’s lymphoma failing to achieve an initial remission. In order to learn more, select Stem Cell Transplantation. Over the last few decades hospital length of stays have been reduced to a few weeks and the risk associated with the HDC and ASCT and not that much different that those from standard chemotherapy.
Treatment of Relapsed Hodgkin’s Lymphoma
Historically, patients that relapse with Hodgkin’s lymphoma 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 25% survive without an additional cancer relapse.
In the 1980's a clinical trial was designed to directly compare HDC and ASCT in order to confirm the benefit of HDC as salvage treatment for patients with relapsed Hodgkin’s lymphoma. The results of this clinical trial were published in 1993 in the journal Lancet and demonstrated that HDC and ASCT cured 5 times as many patients as conventional chemotherapy. High-dose chemotherapy has become the standard salvage treatment for the majority of patients with relapsed Hodgkin’s lymphoma.
Another trial published by researchers from the Royal Marsden Hospital reported long-term data including 195 patients with recurrent Hodgkin’s lymphoma who received an ASCT between 1985 and 2005.
- 61% of patients achieved a complete disappearance of cancer.
- Median survival was nine years.
- Median progression-free survival was three years.
- Five- and 10-year overall survivals were 55% and 49%, respectively.
- 10% of patients developed a second cancer, the most of which were acute myeloid leukemia or myelodysplastic syndromes.
Individuals with Hodgkin's lymphoma failing initial treatment should consider being evaluated at a cancer center or clinic with expertise in HDC and ASCT because these centers produce better outcomes and are dedicated to further improving the way HDC and SCT is utilized. In order to learn more, select stem cell transplantation.
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. Learn about CAR T here:
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.
Adcetris: Adcetris is a precision cancer medicine that targets a protein known as CD30, which is present on HL cells as well as cells from other cancers. Once Adcetris enters CD30-positive cells, it releases the potent chemotherapy drug monomethyl auristatin E. Adcetris when combined with chemotherapy has become a standard treatment for recurrent/refractory HL producing very high response rates and eliminating the need for more toxic chemotherapy regiments.
- Sirohi B, Cunningham D, Powles R, et al. Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma. Annals of Oncology. 2008;19:1312-1319.