We evaluated the safety and efficacy of rituximab(Drug information on rituximab) (Rituxan) in combination with CHOP (cyclophosphamide, doxorubicin(Drug information on doxorubicin) HCl, Oncovin, and prednisone(Drug information on prednisone)) in a study of 40 patients (31 treatment-naive, 9 previously treated) with low-grade/follicular non-Hodgkins lymphoma (LG/F NHL). CHOP was administered at standard doses every 3 weeks for six cycles, along with six infusions of rituximab (375 mg/m²/dose). Two doses of rituximab were given both at the beginning and end of therapy, as well as single doses before the third and fifth cycles of CHOP. Characteristics of the 40 patients include: 21 males and 19 females; median age, 48 years; and stage III/IV disease at diagnosis in 83%.
In general, the majority of adverse events seen were mostly grade 1 or 2. Of overall events, 17% were grade 3 or 4 and consisted primarily of hematologic or infectious toxicities felt to be associated with CHOP chemotherapy. Human antimouse antibody (HAMA)/human antichimeric antibody (HACA) responses were not seen. Although 40 patients were registered, 38 were treated (2 received no therapy).
All treated patients responded (58% complete responses [CRs] and 42% partial responses [PRs]). The overall response rate of the 35 evaluable patients who completed all therapy was 100% (63% CRs, 37% PRs). Median duration of response (DR) and time to progression (TTP) have not been reached after 45.8+ and 47.2+ months, respectively. Twenty-four patients are still in remission beyond 36+ months and up to 54.5+ months.
Of eight bcl-2positive patients, seven converted to polymerase chain reaction (PCR) negativity in blood and marrow (molecular complete remissions). Of these seven patients, six remain in CR and 5 remain PCR negative by serial analyses of blood and marrow aspirates.
CONCLUSION: Rituximab is a novel antitumor agent with good efficacy and minimal toxicity, as demonstrated in recent trials in LG/F NHL. It can be safely combined with CHOP, resulting in a high response rate and a prolonged progression-free survival. The conversion of bcl-2 from positive to negative by PCR in blood and marrow indicates clearance of minimal residual disease, which has not previously been demonstrated with CHOP alone. Rituximab adds therapeutic benefit to CHOP therapy without causing significant additional toxicity.