Long-Term Maintenance with Rituximab in Elderly Patients with Mantle-Cell Lymphoma
Bimonthly maintenance therapy with RTX prolongs the duration of remission and overall survival (OS) in elderly patients with mantel-cell lymphoma (MCL) after induction therapy. Moreover, the initial results in elderly patients with MCL who are treated with induction followed by bimonthly RTX maintenance for 2 years demonstrated a high ORR of 95% (Räty R, et al. Leuk Lymphoma. 2012;53:1920-1928). Räty and colleagues updated their results in a prospective study with completed maintenance therapy in all patients, with a median follow-up time of 6 years for surviving patients (Räty R, et al. ASH 2014. Abstract 1749).
The eligible patients were aged >65 years with histologically confirmed newly diagnosed and previously untreated stage II to stage IV MCL with adequate organ function and performance status. Induction therapy consisted of standard-dose R-CHOP (RTX, cyclophosphamide, doxorubicin, vincristine, and prednisone, cycles 1, 3, 5), RTX plus cytarabine (RTX 375 mg/m2 for 1 dose, cytarabine 1 g/m2 for 4 doses, cycles 2, 4), RTX plus cytarabine and fludarabine (fludarabine 25 mg/m2 for 2 doses, cycles 6-8), and CHOP (cycles 9 and 10). The maintenance treatment for patients in complete remission (CR)/PR included RTX 375 mg/m2 bimonthly for 12 doses. The median follow-up time at the time of this analysis was 70 months (range, 41-113 months) for living patients.
At the time of diagnosis, the median age of the 60 recruited patients was 74 years (range, 65-83 years), 62% were males, 97% had advanced disease (stage III-IV), and 77% had good performance status (0-1). Most (87%) patients had a history of some other notable illness, most typically cardiovascular disease. Another cancer had been diagnosed earlier in 9 patients (prostate, N = 3; breast, N = 3; other, N = 3).
The ORR was 95% (CR, 87%; PR, 8%). Transient grade 4 neutropenia was seen in 20 patients during maintenance with no serious infections. Herpes zoster or varicella zoster infections were recorded in 9 patients. At 6 years (intention to treat), the progression-free survival (PFS) was 64% (median, 97 months; 95% confidence interval [CI], 75-120 months), the event-free survival rate was 59% (median, 95 months; 95% CI, 75-114 months), and the OS rate was 62% (median not reached). The disease-free survival (DFS) rate was 72% at 6 years (median, 91 months; 95% CI, 89-93 months) for 52 patients who had a CR.
Thus, long PFS times and OS rates of >60% at 6 years with a median DFS of >7 years can be achieved with prolonged cytarabine-containing immunochemotherapy followed by 2 years of maintenance with RTX in elderly patients with MCL. Attention should be paid for the development of second malignancies, because myelodysplastic syndromes and acute myeloid leukemia developed in 2 patients, and 6 patients developed carcinomas during follow-up in this elderly patient population.