V. V. Pavlov, N. A. Falaleeva, T. I. Bogatyreva, S. S. Shklyaev, A. Yu. Terekhova, O. M. Volodina
A.F. Tsyb Medical Radiological Research Centre - branch of the NMRC of Radiology of the Ministry of Health of the RF, Obninsk, Russia
Background: Patients with primary refractory or relapsed Hodgkin lymphoma (HL) are expected to have poor outcomes after failure of second-line therapy followed by autologous stem-cell transplantation (ASCT) as well as those who were ineligible for toxic regimens. Bendamustine was only recently approved for the treatment of HL in Russia.
Aims: To identify multiple relapsed patients who may benefit most from bendamustine treatment.
Methods: In this prospective observational study, 47 patients (pts) with relapsed HL lymphoma were enrolled between April 2011 and September 2017; the median age was 36 years and the median number of prior therapies was 3 (range, 1–6); 87% pts had R-stage III-IV, 32% B-symptoms; 55% were not eligible for ASCT (age, multiple relapses, post-RT lung fibrosis), 36% had failed conditioning regimen and 9% relapsed after auto-transplant. Bendamustine (BM) was administered 120 mg/m(2) for two consecutive days with dexamethasone 20 mg i.v. days 1–4, every 21 day, a maximum of 8 cycles. Dose was reduced to 90 mg/m(2) in cases of treatment delays due to neutropenia or thrombocytopenia. Freedom from next failure (FFNF) and overall survival (OS2) were calculated from the start of BM treatment.
Results: A total 196 BM cycles (median 4) were fulfilled in 47 pts, of them 10 pts received BM repeatedly after new relapse (additional 47 cycles). BM treatment was well tolerated. AEs reported were thrombosis, enteropathy, pneumonia, and lockjaw; 7 patients had either delays or reductions in treatment due to thrombocytopenia or neutropenia. Two patients died early due to bleeding from tumor and stroke (OS2 1 and 3 months). A total 27 patients (57%) responded to BM treatment (13 CR/14 PR). In univariate analysis ORR was better in patients with mixed cellularity histology (82%, p = 0.097). Failure rate was higher for nodular sclerosis II (p = 0.001) and B-symptoms (p = 0.064). With a median follow-up of 21 mo. (1–61), OS2 at 2-years for all pts was 57,8% (95% CI 41,8–73,9); for B-pts OS2 was 39,7% vs. 70,8% in A-pts (p = 0.042). FFNF at 2-years was 20,4 (95% CI 7,2–33,6); for B-pts FFNF was 10,0% vs. 29,0% in A-pts (p = 0.076). Median OS2 for all pts was 29 mo. (B-pts 16 mo., A-pts 38 mo.); median FFNF was 11 mo. (B-pts 2 mo., A-pts 15 mo.).
Conclusions: Bendamustine monotherapy is relatively mild treatment demonstrating efficacy and a potential for life prolongation in heavily pre-treated HL patients without B-symptoms at relapse.