Brentuximab Vedotin (BV) an Effective Treatment for Autologous (ASCT) and/or Allogeneic (alloSCT) Transplant naïve Patients with Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) : A retrospective Single-Institution Study

Background: Patients with R/R HL, failing to achieve a complete remission (CR) or a good partial remission (PR) after conventional dose salvage chemotherapy as well as those having severe comorbidities or advanced age, are generally ineligible for a transplant procedure. Furthermore approximately 50% of the patients able to proceed to ASCT, will eventually relapse and will need effective treatment to proceed to alloSCT. BV is a safe and highly effective treatment in R/R HL after ASCT and 75% objective remissions have been reported . Limited data exist regarding BV in transplant naive R/R HL or in R/R HL after ASCT. The aim of our retrospective study was to assess the efficacy and tolerability of BV in R/R HL patients, treated at a single institution, the Istituto Nazionale Tumori of Milan Italy (INT-MI).

Methods: Patients with R/R CD30-positive HL, treated with BV between January 2011 and April 2014 for failure of at least two prior therapies, when ASCT was not considered a treatment option (Group A), or for failure following ASCT (Group B), were included in this retrospective analysis. BV was given at the standard dose of 1.8 mg/kg iv every 21 days. The study protocol was approved by the ethical committee of INT-MI. The primary endpoint of this study was to evaluate efficacy of BV in obtaining FDG-PET remission and in enabling patients to proceed to ASCT or alloSCT. Secondary endpoints included BV toxicity, Progression-free Survival (PFS) and Overall Survival (OS).

Results: Sixteen R/R HL patients for Group A (ASCT-ineligible) and 10 patients for Group B (ASCT failures) were identified. Main characteristics at start of BV were as follows:

Median time from HL diagnosis to BV therapy start was 19 months (range, 8-330) in Group A and 24 months (range, 16 to 254)in Group B, respectively. A median of 6 BV cycles (range, 3 to 19) were administered. Overall response rate in Group A and B was 87.5% and 60%, respectively; CR was documented in 8 patients (50%) in Group A and 2 patients (20%) in Group B. Best response was reported after a median of 3 cycles (range, 2-9). Three patients in Group A and 1 in group B, achieving a negative PET scan, by continuing BV therapy, had PD and were considered transplant ineligible. BV enabled 3 patients in Group A and 1 patient in Group B, achieving CR , to receive a transplant procedure. Moreover two complete responders in Group A underwent ASCT, although PET scan before transplant documented the reappearance of FDG-avid lesions; they are both alive in CR after 14 and 7 months from ASCT, respectively. Two pts in Group B, achieving a PR, underwent alloSCT and relapsed 6 and 11 months after transplant, respectively. Six patients (23%) had grade 3 or higher adverse events (1 sensory peripheral neuropathy, 5 hematological toxicities), no patient discontinued treatment due to toxicity. After a median follow-up of 15 months (range, 3 to 36) since the first BV cycle, median PFS was 5 months and median OS was still not reached.

Conclusions: These data confirm that BV is highly effective in R/R transplant ineligible HL patients, who have generally limited conventional treatment options and a low median OS. BV may overcome chemorefractoriness and enable patients to receive ASCT or allo-SCT, while omitting the significant toxicity of multiagent chemotherapy regimens.