Rituximab: Sustained Remissions in Patients With Relapsed or Refractory Low-Grade or Follicular Non-Hodgkin’s Lymphoma
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
Treatment of low-grade or follicular non-Hodgkin’s lymphoma(NHL) is associated with a high rate of initial response, followed invariably byrelapse. Subsequent remissions occur at a progressively lower rate and withprogressively shorter durations. The median survival time for these patients isestimated at 6.2 years (Surveillance, Epidemiology, and End Results [SEER] andAmerican Cancer Society data). Although advanced-stage low-grade or follicularNHLs are invariably fatal, relapse-free survival can be increased by varioustherapeutic interventions.
However, increasing the intensity or duration of therapy has notbeen demonstrated to prolong survival. More than 50% of patients die within 5years of first relapse. Factors associated with longer survival after relapseinclude complete response (CR) or partial response (PR) following inductionchemotherapy, a duration of response (DR) of 1 year, and age less than 60, asdetermined in an analysis of 466 patients with low-grade or follicular NHLentered in Eastern Cooperative Oncology Group studies. Patients lacking thesefavorable characteristics have poorer prospects for survival, and are candidatesfor more aggressive or experimental salvage therapy for their relapsed disease.
Experience with rituximab (Rituxan) as a single agent or incombination with other therapies has shown that relapsed and refractory patientscan be salvaged, and that sustained remissions can be achieved. In asingle-agent trial (four infusions/wk at 375 mg/m2) of 166 patients, the DR was11.2 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 ongoingremissions in 5 of the 21 responders at 25.5+ to 51.3+ months. In a combinationphase II study, 38 patients received rituximab (375 mg/m2) every week for 4weeks (weeks 5-8) during concurrent treatment (3×/wk for 12 weeks) withsubcutaneous interferon alfa-2a (Roferon-A). The DR is 22.3+ months and the TTPis 25.2+ months, with ongoing remissions in 6 of the 17 responders at 30.5+ to42.8+ months.
In a study of rituximab in combination with CHOP(cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin],prednisone), 40 patients (31 naive, 9 previously treated) received CHOP atstandard doses every 3 weeks for six cycles along with six infusions ofrituximab (375 mg/m2/infusion). Two infusions of rituximab were given both atthe beginning and end of therapy, as well as a single infusion before the thirdand 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 38responders at 47.1+ to 71+ months.
CONCLUSION: Patients with relapsed or refractory low-grade orfollicular NHL who respond to therapy with rituximab can have prolongedunmaintained remissions, for as long as 4 or more years in some patients.
Click here to read Dr. Bruce Cheson's commentary on this abstract.
