ASH 2016 News in Hematology: Lymphoma

ASH 2016 Abstract 1105. Preliminary Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma

Alex F Herrera et al.

Results: Twenty-five pts (60% female) with a median age of 32 years (range, 18-69) have been enrolled to date.  Sixty percent of pts have relapsed disease, 36% have primary refractory disease (failure to achieve CR with frontline therapy, or relapse within 3 months of completing frontline therapy), and 1 pt (4%) has unknown status.  At the time of enrollment, 32% of pts presented with extranodal disease and 16% with bulky disease. 

At the time of the data extract, 23 pts had received treatment.  An increased incidence of infusion-related reactions (IRRs) was observed at the start of combination treatment in Cycle 2 during the BV infusion leading to 1 dose delay.  Premedication with corticosteroids (hydrocortisone 100 mg or equivalent) and antihistamines at Cycles 2-4 was instituted through a protocol amendment.  

Six pts have completed combination treatment, and all have achieved an objective response (ORR, 100%), with 3 of 6 achieving a complete metabolic response (CmR, 50%).  All 6 pts have proceeded directly to ASCT.  Median number of CD34+ cells collected was 12.9 x106 cells/kg (range, 5-26) in a mean number of 1.7 apheresis sessions (range, 1-2).

Adverse events (AEs) for all pts are summarized prior to ASCT.  Eighteen of the 23 treated pts (78%) experienced adverse events (AEs).  Fifteen pts (65%) had AEs ≤ Grade 2 in severity and 3 pts (13%) experienced Grade 3 AEs.  No pts experienced Grade 4 AEs pre-ASCT.  Fatigue was the most common AE occurring in 35% of pts, followed by nausea (26%), rash (22%), dyspnea, myalgia, and pruritus (17% each).  One pt experienced a treatment-related serious adverse event (SAE) of dehydration, hypercalcemia, and acute kidney injury.  Immune-related adverse events (IrAEs) were experienced by 3 pts; 2 pts who experienced Grade 1 rash treated with topical steroids, and 1 pt who experienced Grade 1 hypothyroidism.  No pts have discontinued treatment prematurely.

In addition to Reed-Sternberg cells, CD30 is expressed on activated T cells.  Preliminary biomarker data indicate a BV-induced decrease in the percentage of CD4+ T regulatory (Treg) cells at C1D8, with no decrease in proliferating CD8+ T cells, and no significant decrease observed in the percentage of CD4+ Th1 cells compared to baseline for 5 of 6 pts (83%).  Nivolumab induced a robust expansion of T cells at C1D15. 

Conclusions: Early data suggest the combination of BV and nivolumab is an active and well-tolerated salvage therapy in pts with R/R HL.  While an elevated incidence of IRRs has been observed, toxicities with this regimen appear to be tolerable overall.  The preliminary antitumor activity suggests this combination may be a promising option for R/R HL pts.  Updated results were shared at the time of presentation. 


ASH 2016 Abstract 1108. Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b
Keynote-013 Study

Philippe Armand et al.

Results: At the time of data cutoff on September 27th, 2016, 31 patients were enrolled, and all were evaluable for analysis. Median follow-up duration was 29 months. The median number of prior lines of therapy was 5 (range, 2-15), 74% of patients had failed prior ASCT, and by design 100% had failed prior BV.

Best Overall Response:

Per BICR, median progression-free survival (PFS) was 11.4 months; 6-month and 12-month PFS rates were 66% and 48%, respectively. Median overall survival (OS) was not reached; 6-month and 12-month OS rates were 100% and 87%, respectively.

Conclusions: With nearly 2.5 years of median follow-up, the present results demonstrate that a subset of heavily pretreated patients who failed BV therapy can achieve a long-term response with single-agent pembrolizumab, without consolidative therapy. PD-1 blockade may offer a new treatment paradigm for patients with relapsed/refractory cHL, supporting the hypothesis that this tumor has a genetic dependence on the PD-1 pathway.


CARE Faculty Perspective: PD-1 is a type 1 trans-membrane protein that is encoded by the PDCD1 gene. It is a member of the extended CD28/CTLA-4 immunoglobulin family and represents one of the most important inhibitory co-receptors expressed by T-cells. The checkpoint inhibitors, pembrolizumab and nivolumab, that target PD-1 have shown significant activity in HL (and other lymphomas) with favourable toxicity profiles. These agents represent a new standard of care in patients with relapsed/refractory Hodgkin’s Lymphoma

                       Related PD-1 inhibitor abstracts of interest in HL: 1107. Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase                       2 Keynote-087 Study 1110. Checkmate 205 Update with Minimum 12-Month Follow up: A Phase 2 Study of Nivolumab in Patients with Relapsed/Refractory Classical                               Hodgkin Lymphoma