LY-02. Usage of Brentuximab vedotin with chemotherapy as a “salvage” regimen before autologous stem cell transplantation in classical Hodgkin’s lymphoma patients

Summary

Introduction

Hodgkin’s lymphoma (cHL) is a subtype of lymphoid malignancies characterized by expression of CD30 on Reed-Stenberg cells. Brentuximab vedotin (BV) is an antibody-drug conjugate specific for CD30 consisting of chimeric IgG1 antibody against CD30 covalently attached to the microtubule-disrupting agent monomethyl auristatin E. BV was approved for patients (pts) with relapsed or refractory classical Hodgkin’s lymphoma (r/r cHL) who are not candidates for, or progressed after, autologous stem cell transplantation (ASCT). Bendamustine is a fusion hybrid molecule containing the purine analogue fludarabine and alkylating agent (cyclophosphan). They shown high efficacy and safety as monotherapy [1, 2], also combination of them showed a high activity and is not more toxic than the single agent alone [3]. DHAP (cisplatin, cytarabine, and dexamethasone) is the standard of platinum-based salvage chemotherapy regimens followed by ASCT. The success of ASCT may be predicted by achievement of complete remission (CR) by positron emission tomography (PET) following salvage chemotherapy [4]. Unfortunately, about half of these pts are unable to achieve CR with first salvage. We decided to combine these effective drugs for achievement complete response (CR) before ASCT, confirmed by PET-CT. Our results of ASCT in cHL we compared with historical data [5].

Patients and methods

Twenty-five pts with cHL were included into real data analysis. Median age at the diagnosis time was 24 years (range, 13-50). The first-line chemotherapy was ABVD or BEACOPP (standard; escalated; 14 days) in 23 pts. Two pts <18 years old were subjected to GPON-HD-2002 protocol. At the time of BV treatment, all the pts were >18 years old. The primary resistant pts comprised 60% of the group (15 of 25 cases). 24% of the pts had early relapse of cHL (n=6), and 16% (n=4) exhibited late relapses. BV was used as a “salvage” regimen to ASCT: BV-DHAP, in 15 pts (60%); BV-bendamustine, in 6 pts (24%), and BV as monotherapy was applied in 4 pts (16%). Median number of courses was 3 (range, 2-11). The BV dosage was 1.8 mg/kg in day 1 for all pts; bendamustine was used at 90 mg/kg in day 1 and 2; cisplatin, cytarabine and dexamethasone were also used at standard doses, and DHAP was started on the next day after BV. Stem cells for ASCT were collected by apheresis after a median of 3 cycles (range 1-6) BV- therapy, or after preceding standard chemotherapy. ASCT was planned for 25 pts, but it was performed in 17 cases. All seventeen transplanted pts received BeEAM conditioning. Median number of CD34+ cells was 3.9 (range, 1.0-15) ×10⁶/kg. Characteristics of patient group and complications are presented in Tables 1 and 2.

Table 1. The patient characteristics

Results

At the time of analysis, the median follow-up after BV therapy was 30.4 (8.4-75.5) months. Overall response rate was 96% (24 pts), with complete remission (CR) in 84% (21 pts), and partial remission (PR) in 12% (3 cases). At the moment of analysis, all the patients are alive, progression/relapse was observed in 40% (10 of 25). The median of progression-free survival (PFS) was not reached, and 2-year PFS for all patients was 56.0%. Seventeen pts who received a combination of BV-based therapy + ASCT had the 2-year PFS of 70.6% versus 25% for 8 pts who were not consolidated by ASCT (p=0.013). The therapy was well tolerated at the stage of second-line therapy and ASCT (Table 2).

Table 2. Characteristics of complications in BV- treatment and ASCT

Conclusions

ASCT after high-dose chemotherapy is the standard of care in the second-line treatment of cHL. Addition of BV to these regimens is a promising and safe option that may increase the efficacy of second-line treatment. Multicenter validation studies are required to confirm our preliminary results.

Keywords

Hodgkin lymphoma, autologous stem cell transplantation, brentuximab vedotin, bendamustine.

References

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2. Moskowitz AJ, Hamlin PA Jr, Perales MA, et al. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma.J Clin Oncol 2013; 31: 456-60.
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4. Craig H, Moskowitz AJ et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non–cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma Blood 2012; 7; 1665-1670.
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