Rituximab has been shown to prolong survival when used with chemotherapy in CLL.
The findings come from a comparative analysis of two completed national phase II and phase III clinical trials. The two multicenter clinical trials compare the antibody rituximab plus fludarabine, a chemotherapeutic drug, to fludarabine alone. Rituximab is an antibody-based drug approved for lymphoma. The findings of the two studies show that after an average of 43 months, rituximab plus the drug fludarabine increases progression-free survival by 22 percent and overall survival by 12 percent compared to fludarabine alone.
Rituximab, the mAb targeting CD20, was approved by the US FDA for patients with relapsed low-grade non-Hodgkin lymphoma. Relatively low levels of CD20 are expressed on CLL B cells, compared to normal B or neoplastic B cells of other lymphomas. In addition, soluble CD20 has been demonstrated in plasma of patients with CLL; this may inhibit the capacity of rituximab to bind to CLL B cells, thereby resulting in rapid clearance and negatively affecting pharmacokinetics. Standard-dose rituximab (375 mg/m2 weekly for 4 weeks) has very limited activity for patients with CLL. Dose-intense and dose-dense single-agent rituximab has been shown to increase efficacy but remains experimental. A recent article says: “The maximum dose of rituximab evaluated was 2,250 mg/m2. There is clear evidence of a dose-response relationship. Severe toxicity (grades 3 and 4) noted following the first dose of therapy in variant forms of CLL, namely mantle cell lymphoma and prolymphocytic leukemia, was uncommon in typical CLL. No unusual toxicity was noted at higher doses. Further exploration of the dosing schedule of rituximab in CLL and development of combination therapies is necessary.’
NCCN does list it as an option.
Imrie K, Stevens A, Meyer R, Hematology Disease Site Group. Rituximab in lymphoma and chronic lymphocytic leukemia: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Dec 22. 46 p. (Evidence-based series; no. 6-8). [65 references]
Kahl BS, Hong F, Williams ME, et al. Results of Eastern Cooperative Oncology Group Protocol E4402 (RESORT): A randomized phase III study comparing two different rituximab dosing strategies for low tumor burden follicular lymphoma. Program and abstracts of the 53rd American Society of Hematology Annual Meeting and Exposition; December 10-13, 2011; San Diego, California. Abstract LBA-6.
Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled. Lancet. 2011;377:42-51.
Ardeshna KM, Qian W, Smith P, et al. An intergroup randomised trial of rituximab versus a watch and wait strategy in patients with stage II, III, IV, asymptomatic, non-bulky follicular lymphoma (grades 1, 2 and 3a): a preliminary analysis. Program and abstracts of the 52nd American Society of Hematology Annual Meeting and Exposition; December 4-7, 2010; Orlando, Florida. Abstract 6.
Huhn D, von Schilling C, Wilhelm M, et al. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood. 2001;98:1326–1331.
NCCN, CLL 2018