Abbreviated, Dose Dense Fludarabine and Rituximab for Elderly Patients with Indolent B Cell Malignancies.

Therapy for indolent B cell malignancies is primarily palliative. Therefore limiting toxicities by reducing drug exposure is desirable, particularly in elderly individuals. The combination of fludarabine and rituximab has been extensively used in patients with these disorders. We sought to decrease the number of fludarabine cycles, attempting to maintain the high response rates of this combination by increasing the doses of rituximab and the dose density.

We designed an abbreviated, but dose dense regimen (addFR) consisting of fludarabine 25 mg/m2/d for 5 days on weeks 1, 6 and 11 plus rituximab at 375mg/m2 on weeks 2-5 and 7-10. Maintenance was offered to responding patients with rituximab for 4 weekly doses every 6 months (for 2 years). This schema represents a 50% decrease in the dosage on fludarabine with a 33% increase in the dosage of rituximab compared to the standard regimen. Twelve patients with a median age of 70 years, (range 43 to 85, 9 of the 12 patient are older than 65 years of age) have been treated. Nine patients had chronic lymphocytic leukemia (CLL, n= 5) or small lymphocytic lymphoma (SLL, n= 4). Three patients had marginal zone lymphoma (MZL). Three patients had received prior therapy. Responses were assessed by standard criteria 4 weeks after completion of the planned 11 weeks of therapy.

Two patients are still completing their 11 weeks of therapy. Ten patients have completed the 11 weeks of addFR. They are evaluable for toxicity and responses. Hematological toxicities included neutropenia Grade >III in 2 patients with a single episode of neutropenic fevers requiring hospitalization. One patient with refractory disease was shown to have histological transformation from SLL to a diffuse large B cell lymphoma. All of the remaining 9 patients achieved a complete clinical remission, including 8 patients with CLL/SLL and 1 patient with MZL. With a median follow up of 13 months (range 10 to 23 months); these 9 patients have remained free of disease progression.

addFR seems to be well tolerated and effective even in patients older than 65 years of age. Experience with a larger number of patients and longer follow up is needed.

No relevant conflicts of interest to declare.