ABSTRACT
Five-year overall survival for high-risk Follicular Lymphoma International Prognostic Index follicular lymphoma is only approximately 50% compared with 90% for low risk. To evaluate an approach to improve upon this poor outcome, we completed an exploratory phase II trial of intensified treatment for patients with intermediate and high-risk follicular lymphoma. Front-line treatment with chemo-immunotherapy consisting of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone was followed by radio- immunotherapy with 90-Yttrium ibritumomab tiuxetan consolidation, and 2 years of rituximab maintenance. The 5-year overall survival for intermediate and high-risk patients was 88% and 83%, respectively. Of 33 enrolled patients, 3 were off study before receiving radio-immunotherapy. Three months post radio-immunotherapy, 28/33 (85%) patients had achieved complete response including 6 patients who had only a partial response to chemo-immunotherapy and converted to complete response after radio-immunotherapy. The 5-year progression-free survival for intermediate and high risk was 79% and 58%, respectively. Nine of 19 patients with molecular markers patients remain in molecular and clinical complete remission with a median follow-up of 48 months (range 3-84 months). Post radio-immunotherapy, hematologic toxicities were mostly grade 1 and 2. However, asymptomatic grade 3 or 4 thrombocytopenia and neutropenia occurred in 11%-36% and 10%-24% of patients, respectively. Myelodysplastic syndrome occurred in 1 patient 4 years post treatment. Whereas many patients had prolonged B-cell reduction and low immunoglobulin levels post treatment, previous immunities to rubella were maintained. More aggressive upfront approaches such as this may benefit higher risk follicular lymphoma, but confirmatory trials are required. http://www.clinicaltrials.gov: NCT01446562.
ABSTRACT
Metronomic, low dose chemotherapy may have anti-angiogenic effects and augment the effects of lenalidomide in MDS and CMML. We evaluated the clinical efficacy, tolerability and anti-angiogenic effects of melphalan 2mg and lenalidomide 10mg for 21 days/28 in CMML (n=12) and higher risk MDS (n=8) patients in a prospective phase II study. The primary endpoint was overall response and secondary endpoints included survival, progression-free survival, toxicity and biomarkers of angiogenesis. The median age was 73 years, 55% were pretreated and transfusion dependent. The overall response rate was 3(15%) of 19 evaluable patients but 25% in CMML and 33% in pCMML. Dose reductions and/or delays were common due to myelosuppression. Transient spikes in circulating endothelial cells that declined below baseline were seen in responders and patients with CMML, suggesting anti-angiogenic activity. In conclusion, lenalidomide and metronomic low dose melphalan demonstrate signals of clinical and possible anti-angiogenic activity in patients with pCMML that require future validation. This trial was registered at clinicaltrial.gov under # NCT00744536.
