Choosing several abstracts to highlight among hundreds of interesting presentations on hematologic malignancies from the American Society of Hematology (ASH) annual meeting is a difficult task. Some that may be useful to the practicing clinician confronting the constant dilemmas of relapse and resistance will be referenced here. Typical of ASH, many large studies in lymphoma were presented in 2016.
Pembrolizumab, the immune checkpoint inhibitor of the PD-1/PD-L1 axis, continued to show efficacy in relapsed/refractory Hodgkin lymphoma in the international KEYNOTE-087 (ClinicalTrials.gov Identifier: NCT02453594) study of 210 patients.1 Complete remission was attained in 22% in all 3 treatment arms (2 after autologous stem cell transplantation [ASCT]), similar to experience in their earlier KEYNOTE-013 (ClinicalTrials.gov Identifier: NCT01953692) study. A multicenter study of pembrolizumab in 24 heavily pre-treated patients with mycosis fungoides or Sézary syndrome showed a 38% objective response rate, mostly partial responses.2 These results will lead to combination protocols with interferon gamma.
A French study of 299 adults under 65 years old with mantle cell lymphoma randomized post-auto transplant (after R-DHAP x 4) to rituximab maintenance every 2 months for 3 years versus none. Four-year event-free survival (EFS) was 78.9% vs 61.4%.3
Maintenance after R-CHOP for diffuse large B-cell lymphoma (DLBCL) with lenalidomide for 2 years compared to placebo was reported in 784 previously untreated patients ages 60 to 80.4 With median follow-up over 3 years, there appeared to be an increase in median PFS (not reached versus 68 months for placebo) but with no apparent increase in overall survival. They noted that toxicity of both study and placebo drugs led to stopping in 40-59% of cases.
CAR-T therapy in 14 heavily pre-treated patients with CD19+ follicular lymphoma was reported.5 Nine (64%) achieved a complete response (CR), with 77% progression-free at a median of nearly 1 year, after a single infusion of CTL019 cells.
The effectiveness of ibrutinib in 20 cases of relapsed/refractory central nervous system (CNS) lymphoma was updated, doubling the number reported at the American Society of Clinical Oncology (ASCO) 2016 meeting.6 With “meaningful” cerebrospinal fluid (CSF) concentrations achieved, there were 8 CRs and 7 partial responses (PRs) lasting up to 15 months (median 7.3).
A particularly interesting new agent for proteasome-inhibitor resistant myeloma was reported by a Swiss group based on pre-clinical experience with nelfinavir, an oral HIV protease inhibitor found to increase sensitivity to proteasome inhibitors.7 In combination with bortezomib and dexamethasone in 34 heavily pre-treated, refractory myeloma patients, objective response was seen in 65%.