Median PFS Not Yet Reached After 6 Years in Rituximab/CHOP Trial

BUFFALO, New York—Median progression-free survival has still not been reached after 6 years median follow-up of 40 patients with low-grade or follicular non-Hodgkin’s lymphoma (NHL) treated in the first clinical trial of rituximab (Rituxan) in combination with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], and prednisone), Myron S. Czuczman, MD, reported.

First Clinical Trial of Rituximab/CHOP

In a poster presented at the 43rd Annual Meeting of the American Society of Hematology, Dr. Czuczman reported that 38 patients received treatment and were evaluable for efficacy, 35 of whom had received all six infusions of rituximab and six cycles of CHOP. Two patients were enrolled in the trial but not treated. 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.

Dr. Czuczman said that the overall response rate using intent-to-treat analysis was 95% (55% complete response [CR], 40% partial response [PR]). In patients who completed all therapy the response rate was 100% (63% CR, 37% PR).

Prolonged Progression-Free Survival

"The median duration of response and progression-free survival have not been reached after 63.6+ and 65.1+ months of observation, respectively," Dr. Czuczman reported. "Twenty-one patients are still in remission at 46.8+ and up to 86.3+ months."

Of eight patients who were bcl-2 positive, seven had molecular complete remissions (converted to polymerase chain reaction [PCR] negativity in blood and marrow). Three of these patients remain PCR negative and in CR at 71+, 79+, and 84+ months. Four patients converted to negative and then reverted to positive. Three of these patients remain in CR at 68+, 81+, and 86+ months, and one developed progressive disease at 29 months.

Combination Therapy Is Safe

Adverse events were mostly grade 1 or 2. Seventeen percent of all events were grade 3 or 4 and consisted primarily of hematologic or infectious toxicities felt to be associated with CHOP chemotherapy. Human antimouse antibody/human anti-chimeric antibody responses were not seen.

The only prognostic factor significantly associated with achieving a CR vs a PR was lesion size.

"Rituximab plus CHOP results in a high response rate and a prolonged progression-free survival. Combination therapy is safe and does not cause significant added toxicity. Conversion of bcl-2 from positive to negative by PCR in blood and marrow indicates clearance of minimal residual disease. The prolonged progression-free survival seen in this study exceeds that reported in studies of CHOP alone. This study, by demonstrating safety and efficacy, enabled progression to other phase II and III studies of this combination," Dr. Czuczman said.