Treatment of low-grade or follicular non-Hodgkin’s lymphoma (NHL) is associated with a high rate of initial response, followed invariably by relapse. Subsequent remissions occur at a progressively lower rate and with progressively shorter durations. The median survival time for these patients is estimated at 6.2 years (Surveillance, Epidemiology, and End Results [SEER] and American Cancer Society data). Although advanced-stage low-grade or follicular NHLs are invariably fatal, relapse-free survival can be increased by various therapeutic interventions.
However, increasing the intensity or duration of therapy has not been demonstrated to prolong survival. More than 50% of patients die within 5 years of first relapse. Factors associated with longer survival after relapse include complete response (CR) or partial response (PR) following induction chemotherapy, a duration of response (DR) of 1 year, and age less than 60, as determined in an analysis of 466 patients with low-grade or follicular NHL entered in Eastern Cooperative Oncology Group studies. Patients lacking these favorable characteristics have poorer prospects for survival, and are candidates for more aggressive or experimental salvage therapy for their relapsed disease.
Experience with rituximab(Drug information on rituximab) (Rituxan) as a single agent or in combination with other therapies has shown that relapsed and refractory patients can be salvaged, and that sustained remissions can be achieved. In a single-agent trial (four infusions/wk at 375 mg/m2) of 166 patients, the DR was 11.2 months and the time to progression (TTP) in responders was 13.1 months, with ongoing remissions in 16 of the 76 responders at 20.9+ to 58.2+ months.
In another single-agent trial (eight infusions/wk at 375 mg/m2) of 37 patients, the DR is 13.4+ months and the TTP is 19.4+ months, with ongoing remissions in 5 of the 21 responders at 25.5+ to 51.3+ months. In a combination phase II study, 38 patients received rituximab (375 mg/m2) every week for 4 weeks (weeks 5-8) during concurrent treatment (3×/wk for 12 weeks) with subcutaneous interferon alfa-2a(Drug information on interferon alfa-2a) (Roferon-A). The DR is 22.3+ months and the TTP is 25.2+ months, with ongoing remissions in 6 of the 17 responders at 30.5+ to 42.8+ months.
In a study of rituximab in combination with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin(Drug information on doxorubicin) HCl, vincristine [Oncovin], prednisone(Drug information on prednisone)), 40 patients (31 naive, 9 previously treated) received CHOP at standard doses every 3 weeks for six cycles along with six infusions of rituximab (375 mg/m2/infusion). Two infusions of rituximab were given both at the beginning and end of therapy, as well as a single infusion before the third and fifth cycles of CHOP. The DR is 50.4+ months and the TTP is 52.1+ months; medians have not been reached, with ongoing remissions in 23 of the 38 responders at 47.1+ to 71+ months.
CONCLUSION: Patients with relapsed or refractory low-grade or follicular NHL who respond to therapy with rituximab can have prolonged unmaintained remissions, for as long as 4 or more years in some patients.