HL

Benefit seen in brentuximab vedotin therapy in relapsed, refractory cHL prior to stem cell transplantation

A recent study by Toby Eyre, from the Department of Haematology, Oxford University Hospitals NHS Foundation Trust, and colleagues, evaluated the efficacy of brentuximab vedotin (BV) in Relapsed/Refractory (R/R) classical Hodgkin Lymphoma (cHL) in transplant naïve patients. The results for this UK-wide multicenter retrospective analysis were published in the British Journal of Haematology on 31st August 2017.

The study aimed to investigate the use of BV monotherapy on patient outcomes before Stem Cell Transplantation (SCT). The study included 99 patients who were transplant naïve with R/R cHL, all of whom had received two prior lines of therapy and were treated with BV monotherapy before intending to receive consolidating SCT. The analysis took place between May 2011 and July 2016.

Key Findings:
  • Median age = 32 years (range, 13-70)
  • Treatment: BV monotherapy 1.8 mg/kg once every three weeks until SCT consolidation, progression, toxicity or death
Efficacy:
  • Median 12-month follow-up (0.4–56.7)
  • Median PFS = 5.6 months (95% CI, 4.4–12.2)
  • Median OS = 37.2 months (95% CI, 18.3–not reached (NR))
  • ORR = 56% (29% CR and 27% PR)
  • Thirty-four patients (34%) had consolidation SCT after successful BV therapy
  • Twenty-seven patients (27%) received deferred SCT therapy
  • Thirty-eight patients (38%) did not receive SCT therapy (due to inadequate treatment response)
  • No SCT
    • Median PFS = 3.0 months (95% CI, 2.5–4.4)
    • Median OS = 12.2 months (95% CI, 8.1–18.3)
  • Autologous SCT
    • Median PFS = NR (95% CI, 17.0 months–NR)
    • Median OS = NR (95% CI, 27.0 months–NR)
  • Allogenic SCT
    • Median PFS = NR (95% CI, 5.6 months–NR)
    • Median OS = NR (95% CI, 37.2 months–NR)
Safety:
  • No Adverse Events (AEs) reported in 63 patients (64%)
  • The most common grade 3 or grade 4 AEs were neutropenia (n=6), non-neutropenic infection (n=4), and sensory peripheral neuropathy (n=2)
  • One death was reported following non-neutropenic infection

 

Conclusion

This retrospective analysis provided insight as to the benefits of BV monotherapy for patients with R/R cHL before consolidative SCT. Improved PFS and OS were seen with patients who went on to receive SCT compared with those not receiving SCT therapy, although the differences in outcomes between allogenic and autologous SCT were not clear. The safety profile of BV was favourable with low incidence of AEs, supporting the non-toxic use of BV prior to SCT, although one death was reported in this cohort. The authors concluded that because patients who did not go on to receive SCT had very poor outcomes, there is an unmet clinical need to investigate further therapies for this subgroup.

Abstract

Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT. We performed a UK-wide retrospective study of 99 SCT-naïve relapsed/refractory cHL. All had received 2 prior lines and were deemed fit for transplant but had an insufficient remission to proceed. The median age was 32 years. Most had nodular sclerosis subtype, Eastern Cooperative Oncology Group performance status 0-1 and advanced stage disease. The median progression-free survival (PFS) was 5·6 months and median overall survival (OS) was 37·2 months. The overall response rate was 56% (29% complete response; 27% partial response). 61% reached SCT: 34% immediately post-BV and 27% following an inadequate BV response but were salvaged and underwent deferred SCT. Patients consolidated with SCT had a superior PFS and OS to those not receiving SCT (P < 0·001). BV is an effective, non-toxic bridge to immediate SCT in 34% and deferred SCT in 27%. 39% never reached SCT with a PFS of 3·0 months, demonstrating the unmet need to improve outcomes in those unsuitable for SCT post-BV.

References
  1. Eyre TA. et al. Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naïve setting. British Journal of Haematology. 2017 Aug 31. DOI: 10.1111/bjh.14898. [Epub ahead of print]