High Intermittent Dose of Chlorambucil Associated with Rituximab Is a Promising Treatment of Elderly Patients with Indolent Lymphoma.

Indolent lymphoma cannot be cured in elderly patients. Applied treatments therefore aim at reaching the best response with as little as possible adverse effects to ensure the best survival. Because of their toxicities, multiagent cytotoxic chemotherapies are usually not applicable to elderly patients. The addition of rituximab to combination chemotherapy has improved treatment outcomes of indolent lymphomas. We used our experience of high intermittent dose of Chlorambucil in CLL¹ to control indolent lymphoma in combination with rituximab in elderly patients. The aim of this study was to evaluate, in a retrospective manner, the efficacy and toxicity of this strategy.

Patients aged over 65 years with an indolent lymphoma, at diagnosis or in relapse, were treated in our institution by the RCM regimen. They received as “induction” an association of Chlorambucil (12 mg/D for 4 weeks D1 to D28), Rituximab (375 mg/sqm D 1 and D8) and Methylprednisolone (24 mg/D for D1 to D28). Responders (Cheson criteria 1999) completed this schedule by five monthly maintenance cycles associating Chlorambucil (12 mg/D for 10 days) and Rituximab (375 mg/sqm on D1).

Between 2005 and 2009, twenty two patients, 12 males and 10 females were treated with the RCM regimen, 14 at diagnosis and 8 at relapse [median number of previous line = 1 (1-4)]. The median age was 77 years (66-89). The diagnosis of lymphoma was marginal zone for 10 patients (8 nodal forms and two Malt), follicular for 5, classic form of mantle-cell for 4, small lymphocytic for 3. Eighteen patients were at Ann Arbor stage III-IV (82%), 14/21 had high level LDH (65%), 9/22 had a PS of 2 or more (41%). Low, intermediate and high aaIPI scores were found in 8, 8 and 6 patients respectively. A high tumour burden was observed in 18/22 patients (82%).

Among the 22 patients, 16 finished the entire treatment plan, 4 stopped early in one case because of progression and in 3 cases for grade 3 toxic events (2 skin rashes related to Chlorambucil and 1 neutropenia). Two patients are still under treatment. Grade 3 toxicities were uncommon, involving 2 patients with neutropenia, 2 with skin rashes and 2 with infection (one septicaemia and 2 pneumonias). The overall response rate (ORR) was 90% (20/22) with 14 patients in CR (64%) and 6 in PR (27%). Two patients progressed during treatment.

The aaIPI appeared as the best prognostic factor of response:, 13/16 patients (81%) with score 1 or 2 reached CR versus only 2/6 patients (33%) with score 3. With a median follow-up of 9 months (4-49) all patients but one are alive and the 14 patients in CR have not relapsed after 6 to 49 months.

High intermittent dose of Chlorambucil associated with Rituximab offers a promising high ratio of efficacy/tolerance in elderly patients with indolent lymphoma.

1 Pegourié-Bandelier B, Cancer 1995, 75 (12), 2853-61

Gressin:celgene: Consultancy.