Oral Chlorambucil and Prednisone With Rituximab as Initial Chemotherapy for Low-Grade Non-Hodgkin’s Lymphoma: A Phase II Trial

March 1, 2001

Rituximab has been an effective treatment for chemotherapy-refractory low-grade non-Hodgkin’s lymphoma (NHL). The integration of rituximab (Rituxan) into standard first-line oral chemotherapy for low-grade NHL was initiated in order to

Rituximab has been an effective treatment forchemotherapy-refractory low-grade non-Hodgkin’s lymphoma (NHL). Theintegration of rituximab (Rituxan) into standard first-line oral chemotherapyfor low-grade NHL was initiated in order to evaluate the response rate andtoxicity of this non-cross-resistant combination.

Chemotherapy-naive patients with low-grade non-Hodgkin’slymphoma requiring treatment were eligible for study. All patients were treatedwith six cycles of chlorambucil (Leukeran) at 0.1 mg/kg po days 1-5 andprednisone at 100 mg po days 1-5. Cycles were repeated at 28-day intervals.Rituximab at 375 mg/m2 was administered intravenously on days 2, 9, 16, and 23of the first cycle only. Between June 1999 and May 2000 20 patients wereentered.

Patients included 10 males and 10 females, with an age range of39 to 87 years. Histology was as follows: follicular cell carcinoma (FCC) smallcleaved (8), FCC mixed (8), FCC large (2), and FCC unspecified (2). Patientswere classified as stage I (2), II (7), III (7), or IV (4). Median time on studyis 171 days (range: 55 to 386 days). Response evaluation is done prior to cycle3 and 1 month following the completion of therapy.

All patients have completed at least two cycles of therapy andare evaluable for response. The overall response rate is 80% (4 completeresponses [CR], 12 partial responses [PR], 2 stable disease, 2 inevaluable). Oneinevaluable patient had non-neutropenic sepsis and death at day 8 of cycle 1,and the other had a severe anaphylactoid reaction to rituximab necessitatingdiscontinuation of therapy. Other grade III toxicities include one deep-veinthrombosis, one septicemia during cycle 6, and one central nervous system (CNS)bleed with normal platelet count.

To date only one objective responder has progressed.Additionally, there was one death on treatment, and 5 patients are alive and offstudy (1 rituximab reaction, 1 CNS bleed, 3 progressive disease). Fourteenpatients are alive and on study (6-month follow-up: 5 CR, 1 PR, 8 too early toassess).

CONCLUSION: Combination biological and chemotherapy in thissetting will require long-term follow-up and formal comparison to chemotherapyalone in the treatment of low-grade NHL.

Click here to read Dr. Bruce Cheson's commentary on this abstract.