Lenalidomide plus CHOP: Acceptable toxicity in elderly with angioimmunoblastic T-cell lymphoma
Lenalidomide, given for 14 days in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), has demonstrated acceptable toxicity in the REVAIL study in elderly patients with angioimmunoblastic T-cell lymphoma (AITL), with efficacy results similar to reports from previous studies.
The multicentre, open-label, phase II study included 80 elderly patients (median age, 69 years) with AITL or peripheral T-cell lymphoma derived from T-follicular helper cells who had received no prior treatment except steroids within 15 days. The patients were treated with eight cycles of lenalidomide (25 mg/day on days 1–14) in addition to the CHOP 21 regimen, with intrathecal methotrexate for central nervous system prophylaxis, low-molecular-weight heparin for thromboprophylaxis, as well as filgrastim on day 6. [Lemonnier F, et al, ASH 2018, abstract 999]
“Forty-five patients [58 percent] completed the planned eight cycles of therapy. The median dose of lenalidomide was 2,275/2,800 mg, or 81 percent of the planned dose. Doxorubicin and cyclophosphamide were administered at 98 percent and 97 percent of the planned dose, respectively,” reported investigator Dr Francois Lemonnier of the Hôpital Henri Mondor & Université Paris Est Créteil, Créteil, France. “The mean interval between cycles was 22.4 days.”
“Toxicity was within the expected range, with grade 4 neutropenia occurring in 70.5 percent of patients and grade 4 thrombocytopenia occurring in 30.8 percent of patients,” he noted. “Thrombosis occurred in 10 percent of the patients. Four secondary primary malignancies were reported, including one case of myelodysplastic syndrome occurring during therapy, and one case each of acute myeloid leukaemia, marginal zone lymphoma and neuroendocrine tumour occurring at 16–36 months.”
The primary endpoint of complete metabolic response was observed in 34 patients (43.6 percent), while partial metabolic response was observed in three patients (3.8 percent). “The overall response rate [ORR] was 47.4 percent,” said Lemonnier. “Twenty-two patients [28 percent] had stable or progressive disease.”
After a median follow-up of 31.5 months, median progression-free survival (PFS) was 13.7 months (95 percent confidence interval [CI], 9.8 to 32.3), while median overall survival (OS) was 50.6 months (95 percent CI, 22.8 to not available). The 2-year PFS rate and OS rate were 42 percent and 60.1 percent, respectively.
“DNMT3A mutations were found to be associated with refractoriness to therapy,” said Lemonnier. “The ORR for patients with mutated DNMT3A was 30 percent, compared with 60 percent in patients without such mutation [odds ratio (OR), 0.297; 95 percent CI, 0.090 to 0.887; p=0.035]. Patients with DNMT3A mutations also had significantly shorter PFS [p=0.04] and a trend towards a shorter OS [p=0.032].”“Patients with a combination of TET2, IDH2 and DNMT3A mutations had significantly shorter OS than those without such mutations [p=0.0163],” he continued.