The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can’t be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of “naked” or “conjugated” anti-CD20 monoclonal antibodies as a single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role in the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs, and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.
Background and objectives
The standard first-line therapy for patients with DLBCL includes R-CHOP or CHOP-like regimens; although these regimens are highly effective in the majority of DLBCL patients , elderly “unfit” patients do not tolerate these schedules and usually receive palliative therapy with a consequent dismal prognosis. Several polychemotherapy regimens combining low toxicity and a substantial anti-lymphoma activity have been tested in this clinical setting. In the pre-rituximab era, VEMP (etoposide, cyclophosphamide, mitoxantrone, prednisone) polychemotherapy was investigated initially in relapsed/refractory patients and subsequently as first line therapy and displayed fairly good outcomes. In this study, we present data from an Italian single-center experience evaluating the efficacy and tolerability of the association of Rituximab with VEMP (R-VEMP) in patients not eligible for standard R-CHOP therapy or its modifications (for example R-miniCHOP) because of age and/or comorbidities.
Design and Methods
From October 2006 to November 2012, 34 untreated patients aged 66 years and older (median age: 79) with DLBCL (26% GC, 48% non-GC, 26% ND) were treated with a combination chemotherapy including etoposide 150 mg/m2 day 1; cyclophosphamide 650 mg/m2 day 1; mitoxantrone 12 mg/m2 day 1; prednisone 60 mg/m2 day 1-5; rituximab 375 mg/m2 day 0). Sixty-eight percent of patients had high Charlson Comorbility Index; 62% had Ann Arbor stage III/IV disease; 47% had high or intermediate-high International Prognostic Index score.
Results
Twenty-six patients (76%) completed the scheduled treatment (4 or 6 cycles). The Overall Response Rate (ORR) was 71%: 19 patients (56%) obtained a Complete Response (CR), 5 (15%) achieved a Partial Response (PR); 3 patients (9%) were in stable disease and 7 (20%) had a progressive disease (among these latter, 6 patients were intermediate-high or high IPI score and had extranodal disease; all of these patients had high Charlson Comorbility Index). After a median follow-up of 20 months, 15 patients (44%) maintained a CR and only one patient relapsed within 14 months after achieving a CR. In this setting of patients the median Overall Survival (OS) was 20 months (range 1-78), the Event Free Survival (EFS) was 6 months (range 1-41). The treatment was well tolerated without therapy related mortality. Among the adverse events, the most common were: grade 3-4 temporary neutropenia (71%), grade 2 transitory anemia (29%) and febrile neutropenia (20%). G-CSF was administrated to 29 patients (85%) and erythropoiesis stimulating agents to 8 patients (24%).
Conclusions
These data suggest that R-VEMP is a well-tolerated and highly effective regimen in elderly “unfit” patients with DLBCL and could offer a valuable alternative choice for those patients not eligible for more toxic first line protocols. Considering the high rate of serious adverse events and the difficulty to completely administer the scheduled cycles, standard R-CHOP or CHOP-like therapy is applied with much less frequency to elderly unfit patients. R-VEMP could represent a reasonable regimen that warrants to be further explored, as an additional therapeutic option in order to overcome the low survival rate observed in this subgroup of patients.
Disclosures:
No relevant conflicts of interest to declare.
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