The Challenges of Hodgkin Lymphoma in the Elderly

As the authors have correctly pointed out, Hodgkin lymphoma (HL) in elderly patients is an orphan disease that has been the subject of very few specific studies, particularly regarding treatment. Because HL is usually a disease of patients aged between 20 and 40 years, who typically present with a localized stage and respond very well to ABVD therapy (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) plus radiation, the outlier patients tend to be forgotten. As shown by Evens and colleagues, however, this is not true-the group of HL patients older than age 60 is more important than the “classical” group of young patients (as illustrated by the authors in Figure 1 of their article).

Presentation and Prognostic Factors

The characteristics of these patients are different from those of classical HL in young patients: more patients present with stage III and IV at time of diagnosis, more present with B symptoms, and fewer have bulky tumor (Table 1 of the paper). Furthermore, these elderly patients are more likely to have concomitant diseases that may affect their performance status and ability to tolerate standard therapies, and thus further decrease response rates and alter the outcome (as in other curable cancers such as diffuse large B-cell lymphoma).[1]

Overcoming Treatment Challenges

Because of the comorbidities often present in elderly patients, physicians tend to use “specially designed” regimens in this population. However, these specially designed regimens usually involve lower doses of effective drugs or replace effective but toxic drugs with less toxic but less effective drugs. This is another reason older patients have a worse outcome than young patients treated with ABVD. In diffuse large B-cell lymphoma, several studies have shown that older patients must be treated like their younger counterparts and that this approach has improved overall survival.[2] Randomized studies addressing this dose-intensity question are lacking in elderly HL patients. However, reasons not to use ABVD are probably not so frequently encountered, and ABVD must stay the standard for fit patients, whatever their age.

All of the drugs in the ABVD regimen may be of concern. However, the use of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) has shown that this doxorubicin dose is feasible without cardiac toxicity in the great majority of elderly patients.[3] In case of neurologic toxicity, the vinblastine dose may be slightly decreased or vinblastine may be replaced by etoposide, a drug without neurologic toxicity and that has shown activity in HL patients. Bleomycin is probably the most problematic drug because of its pulmonary toxicity in patients with previous pulmonary dysfunction. However, if this toxicity occurs, bleomycin may be stopped without altering the efficacy of this regimen once a response has been obtained. The major toxicity associated with dacarbazine is nausea and vomiting, but it is usually not difficult to reduce this toxicity with our current armamentarium.

In the case of severe comorbidities, a more tolerable regimen should be used. The Groupe d’Etude des Lymphomes de l’Adulte (GELA) has used a regimen (ABVPP) in which dacarbazine is replaced by procarbazine (Matulane), with better tolerability and at least identical results in an elderly population.[4,5] Other regimens have been described but must be tested in comparison with the standard ABVD combination before being recommended.

The Orphan Disease Dilemma

As to the title of this review-“Hodgkin Lymphoma in Older Patients: An Uncommon Disease in Need of Study”-it’s worth noting that Hodgkin lymphoma is an orphan disease by itself, not only in elderly patients. In fact, outside the group of young patients with localized disease for whom the standard regimen combines ABVD and radiation therapy and the cure rate is over 90%, there is no standard treatment for young or elderly patients with disseminated disease, or for relapsing patients. These patients have a much lower survival rate, and certainly new approaches can and should be developed. Very few new drugs or regimens have been studied specifically in HL patients, in contrast with the numerous monoclonal antibodies or targeted drugs available for B-cell lymphomas.

An urgent effort is needed from the large cancer groups to specifically design studies targeting this population of elderly patients (as well as relapsing patients) to try to establish standards with better efficacy. The only good salvage approach we currently have includes a regimen like DHAP (dexamethasone, high-dose cytarabine [Ara-C], cisplatin [Platinol]) or MINE-R (mitoguazone [Apep], ifosfamide, vinorelbine [Navelbine], radiation) followed by high-dose therapy with the BEAM regimen (carmustine [BiCNU], etoposide, cytarabine, melphalan) and autologous transplant. This is clearly not feasible in elderly patients with HL. As we begin to know more about the pathology of HL, specific targeted drugs will need to be developed.

References:

References

1. Thieblemont C, Coiffier B: Lymphoma in older patients. J Clin Oncol 25:1916-1923, 2007.
2. Coiffier B: State-of-the-art therapeutics: Diffuse large B-cell lymphoma. J Clin Oncol 23:6387-6393, 2005.
3. Feugier P, Van Hoof A, Sebban C, et al: Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: A study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23:4117-4126, 2005.
4. Ferme C, Mounier N, Casasnovas O, et al: Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: A study by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood 107:4636-4642, 2006.
5. Ferme C, Sebban C, Hennequin C, et al: Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin’s disease: Results of the Groupe d’etudes des Lymphomes de l’Adulte H89 trial. Blood 95:2246-2252, 2000.