In 2013, an estimated 15,680 people in the United States will be diagnosed with chronic lymphocytic leukemia (CLL), and 4580 will die of the disease. The mean age at diagnosis is 72 years, and the 5-year survival rate is 82%.1
Patients with indolent disease are able to go long periods with a watch-and-wait approach. The criteria for treatment require some of the following symptoms: rapidly progressing disease, ie, bulky lymphadenopathy and risk of complications from lymphadenopathy; cytopenias; B symptoms, ie, weight loss of greater than 10%, drenching night sweats, extreme fatigue; and other signs of failure to thrive.
Chlorambucil was a first-line choice in the treatment of CLL. Combination chemotherapy – fludarabine, cyclophosphamide, and rituximab (FCR) – showed longer progression-free survival; however, median survival was not improved when compared with chlorambucil. FCR is considered a toxic treatment due to its aggressive side effect profile, and its use became problematic for the elderly and patients with significant comorbidities. Toxicities forced treatment holds, dose reductions, and discontinuation of therapy, thus decreasing efficacy.
Bendamustine was approved for use in CLL in 2008 as a result of a study comparing bendamustine and chlorambucil. In a cohort of 301 patients, 153 patients received single-agent therapy with bendamustine and 148 patients received chlorambucil. The bendamustine dosing was 100 mg/m2 on days 1 and 2 of a 28-day cycle, and chlorambucil was dosed at 0.8 mg/kg po on days 1 and 15 every 28 days. Bendamustine as monotherapy showed a higher overall response rate than chlorambucil alone. Median time to progression was 18 months for bendamustine versus 6 months for chlorambucil. The toxicity profile proved to be greater with bendamustine than with chlorambucil, but better than with FCR. The most common side effects were hematologic toxicities, infections, nausea, vomiting, and an increased incidence of tumor lysis syndrome.2
Bendamustine Use in B-Cell Non-Hodgkin Lymphoma
B-cell lymphoma is the most common type of lymphoma. Approximately 69,740 cases of both B- and T-cell lymphoma was diagnosed in 2012.1 Treatment depends on the type and staging of the disease. Even with current treatment regimens, non-Hodgkin lymphoma (NHL) and mantel cell lymphoma remain incurable.2
The addition of rituximab to chemotherapy regimens has increased efficacy of treatment with adjunct chemotherapy. In 2008, bendamustine was approved for second-line treatment in patients who have failed first-line treatment with a rituximab or rituximab-containing regimen or were declared to have rituximab-resistant disease.3 Patients who fail first-line treatment or become resistant tend to have lower response rates to subsequent treatments.2 A single-arm study of 100 patients who relapsed within 6 months of rituximab as monotherapy or combination therapy were treated with bendamustine 120 mg/m2 on days 1 and 2 of a 21-day treatment cycle. Sixty-seven percent of patients had advance disease and had received a median of 2 previous treatments. An overall response rate of 74% was seen in patients who received bendamustine in this setting.3
Bendamustine has significant activity in CLL and NHL, with an acceptable toxicity profile. The goal of treatment is to maximize response and minimize toxicities while improving quality of life. Careful monitoring of patients is imperative. Supportive patient care for hematologic toxicity and nausea and vomiting and prophylaxis infection treatment are key to maintaining patient safety goals. Ongoing studies will provide data from the use of bendamustine in combination therapy. Some of the purposed studies combine rituximab, ofatumumab, lenalidomide, and fludarabine.2
References
1. American Cancer Society. Cancer Facts & Figures 2013. Atlanta, GA: American Cancer Society; 2013. www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf. Accessed February 6, 2013.
2. Van der Jagt R, Laneuville P, Macdonald D, et al. A Canadian perspective on bendamustine for the treatment of chronic lymphocytic leukemia and non-Hodgkin lymphoma. Curr Oncol. 2012;19:160-168.
3. Kahl BS, Bartlett NL, Leonard JP, et al. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010;116:
106-114.