Although the majority of patients with Classical Hodgkin lymphoma (HL) are cured with first-line combined chemotherapeutic regimens, up to 15-30% of patients have relapse or refractory disease. Brentixumab vedotin (BV) is an anti-CD30 monoclonal antibody conjugated to the monomethyl auristatin E, which is a disrupting agent for microtubule function. BV monotherapy has 27% -35% CR rates in the second line setting prior to ASCT. Bendamustine is a fusion hybrid analogue and an alkylating agent containing purine analog; it can be used in relapsed non-HL, was also evaluated in relapsed/refractory HL in the post-ASCT setting; the overall response and CR rates were reported 53% and 33%. In a phase 1-2 study, the complete response was achieved 72.6% and 92.5% with the combination of brentuximab vedotin plus bendamustine as the first salvage treatment for relapse refractory HL.
In our study, we aimed to evaluate the response rates of brentuximab vedotin plus bendamustine combination experience in patients with relapsed or refractory HL.
In this a single center retrospective study, between May 2018 and February 2019, we evaluated 17 patients for the treatment. The eligible patients were aged 18 years or older, had histologically confirmed relapsed or refractory Hodgkin's lymphoma. They received a dose of 1.8 mg/kg of brentuximab vedotin intravenously on day 1 of a 21 day cycle, plus one dose of 90 mg/m2 bendamustine intravenously on each of days 1 and 2 of a 21 day cycle Response evaluation was performed after at least 2 cycles of combination treatment.PET-CT scans were done 4 to 6 weeks after the treatment for response assessment.
Seventeen patients were enrolled and the median age was 39 (19-77). 61.6% of the patients were nodular sclerosing histologic subtype. At the time of diagnosis 71 % of the patients had advanced stage, 18% of the patients had bulky (> 7 cm) disease. 60 % of the patients were primary refractory. The Brentixumab and bendamustin combination treatment was given as median 3rd line treatment (at least 2; maximum 7 lines). The objective response rate was 86.6% and complete response rate was 60 % as a result of the combination treatment. Refractory disease was observed 13.3% of the patients. Two patients experienced grade 3 pneumonia, two patients had neutropenia, one patient had anemia, one patient had severe motor neuropathy, two patients had diffuse hyperemic rash. No severe anaphylactic reaction was observed.
Various salvage regimens are preferred for relapsed refractory (R/R) Hodgkin lymphoma patients, the CR rates varies between %20-60. BV monotherapy was achieved 68% of total response rate and 35% of complete response rate before ASCT in R/R group. Considering the depth of response before ASCT and PET negativity as a predictive factor, the combination of BV and bendamustine as a salvage therapy for patients with R/R HL was achived high CR rates (72.6%) and overall response rates (92.5%). In general, the combination was well tolerated. In our study, 86.6 % overall response rates and 60% CR rate were achieved. In conclusion, the combination of BV and bendamustine therapy in relapsed/refractory HL is highly effective and has a manageable toxicity profile and it requires outpatient administration and reduce hospitalization. This combination can be evaluated in the patients who are not candidate for standard salvage treatment regimens due to comorbidity. It can be used as a bridge therapy especially proceeding ASCT associated with high response rates.