R-GCVP as First Line Treatment for DLBCL Patients with Cardiac Comorbidity

Mohamed Alorabi

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), with an incidence that increases with age to >100 cases per 100,000 in people age >80 years. By the year 2015, the population of age >65 years is predicted to rise by 22%, and of age >80 years by 50%.

The treatment of choice for newly diagnosed patients with advanced DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemo-immunotherapy, which results in 5-year survival among patients age >65 years in the range of 60% (1). Doxorubicin is one of the key components of the R-CHOP regimen, but it is known to be associated with an increased risk of cardiac toxicity, particularly congestive heart failure, with increasing cumulative dose. The risk of cardiomyopathy is greatly enhanced by the attendant cardiac risk factor of hypertension and in a series of 6,388 patients age >65 years with DLBCL, cardiac risk factors were common; 32% patients had diabetes mellitus, and 73% had hypertension (2). As a result, older DLBCL patients with underlying heart disease are often precluded from a curative treatment. Gemcitabine is a chemotherapeutic drug that in combination with platinum and methylprednisolone has shown promising efficacy in the setting of both relapsed/refractory NHL and HL (3). Cardiac toxicity is a rare complication of gemcitabine.

In a recently published phase II trial, sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle. Median age was 76.5 years. All patients had advanced disease; 27 (43.5%) had left ventricular ejection fraction of <50%, and 35 (56.5%) had borderline ejection fraction of >50%, but ≤55%, and comorbid cardiac risk factors such as ischemic heart disease, diabetes mellitus, or hypertension. Primary end point was overall response rate at the end of treatment. Thirty-eight patients (61.3%) achieved disease response (complete response [CR], n=18; undocumented/unconfirmed CR, n=6; partial response, n=14). Two-year progression-free survival for all patients was 49.8%, and 2-year overall survival was 55.8%. Thirty-four patients experienced grade ≥3 hematologic toxicity. There were 15 cardiac events, of which seven were grade 1 to 2, five were grade 3 to 4, and three were fatal, reflecting the poor cardiac status of the study population (4).

R-GCVP seems to be well-tolerated treatment for patients with DLBCL for whom anthracycline- containing immunochemotherapy was considered unsuitable because of coexisting cardiac disease.

Discussion questions:

What is the best management in your opinion for DLBCL patients with cardiac problems?
Do you predict that R-GCVP will be effective regimen for this group of patients in the future?

References:

  1. 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 2005;23(18):4117-26.
  2. Hershman DL, McBride RB, Eisenberger A, et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2008; 26(19):3159-65.
  3. Ng M, Waters J, Cunningham D, et al. Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma. Br J Cancer 2005; 92(8):1352-7.
  4. Fields PA, Townsend W, Webb A, et al. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol 2014; 32(4):282-7.

The content of this article reflects the personal opinion of the author and is not necessarily the official position of the European Society for Medical Oncology.

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