Manali K. Kamdar

PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: High response rate but frequent GVHD

Given the limited treatment options for relapsed lymphoma post-allogeneic hematopoietic cell transplantation (post-allo-HCT) and the success of programmed death 1 (PD-1) blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label after allo-HCT. To characterize the safety and efficacy of PD-1 blockade in this setting, we conducted a multicenter retrospective analysis of 31 lymphoma patients receiving anti-PD-1 mAbs for relapse post-allo-HCT. Twenty-nine (94%) patients had cHL and 27 had ≥1 salvage therapy post-allo-HCT and prior to anti-PD-1 treatment. Median follow-up was 428 days (range, 133-833) after the first dose of anti-PD-1. Overall response rate was 77% (15 complete responses and 8 partial responses) in 30 evaluable patients. At last follow-up, 11 of 31 patients progressed and 21 of 31 (68%) remain alive, with 8 (26%) deaths related to new-onset graft-versus-host disease (GVHD) after anti-PD-1. Seventeen (55%) patients developed treatment-emergent GVHD after initiation of anti-PD-1 (6 acute, 4 overlap, and 7 chronic), with onset after a median of 1, 2, and 2 doses, respectively. GVHD severity was grade III-IV acute or severe chronic in 9 patients. Only 2 of these 17 patients achieved complete response to GVHD treatment, and 14 of 17 required ≥2 systemic therapies. In conclusion, PD-1 blockade in relapsed cHL allo-HCT patients appears to be highly efficacious but frequently complicated by rapid onset of severe and treatment-refractory GVHD. PD-1 blockade post-allo-HCT should be studied further but cannot be recommended for routine use outside of a clinical trial.

POLATUZUMAB VEDOTIN PLUS BENDAMUSTINE AND RITUXIMAB OR OBINUTUZUMAB IN RELAPSED/REFRACTORY FL OR DLBCL: UPDATED RESULTS OF A PHASE 1B/2 STUDY

NHL. Interim data are reported here. Methods: Relapsed/refractory HL or NHL pts who have no available established therapies known to provide clinical benefit at their current disease state are being recruited to a dose escalation (part 1) and dose expansion (part 2) phase I study. The primary objectives of part 1 are to assess the safety and tolerability and define a maximum tolerated dose (MTD) of ADCT‐301 to recommend for part 2. The primary objective of part 2 will be to evaluate the safety and tolerability of ADCT‐301 at this recommended dose. Efficacy (overall response rate, duration of response, progression‐free survival, subtype‐specific responses, and overall survival), pharmacokinetics, pharmacodynamics, and anti‐ drug antibody activity are also being assessed. Patients receive IV infusions of ADCT‐301 every 3 weeks (1 cycle) from a starting dose cohort at 3 μg/kg with subsequent cohorts enrolled at escalating doses according to a continual reassessment method. No intra‐patient dose escalation is allowed. Results: As of 8 Feb 2017, 18 pts (11 male, 7 female; median age: 44 yrs [range 23–79]; median number of previous therapies: 4 [range 1–10]) with HL (n = 10) or NHL (n = 8) have been treated with ADCT‐301 doses ranging from 3 to 45 μg/kg (median number of cycles: 2 [range 1–12]; median duration of treatment: 43 days [range 21–251]). A total of 4 pts have reported DLTs: 1 with maculopapular rash at 8 μg/kg; 1 with oral mucositis and small bowel enteritis at 20 μg/kg; 1 with elevated creatine phosphokinase at 30 μg/kg; and 1 with maculopapular rash and pruritus at 30 μg/kg. Treatment‐emergent adverse events have been reported in 16 (88.9%) pts, including anemia (4 [22.2%] pts), pruritus (4 [22.2%] pts), and maculopapular rash (4 [22.2%] pts). The first disease responses were seen at 30 μg/kg: 1 HL pt achieved a complete response, and 1 HL pt achieved a partial response. A total of 6 pts achieved stable disease as their best response including 1 HL pt at 13 μg/kg who has remained progression‐free for >30 weeks (>10 cycles). Conclusions: This dose escalation and expansion study will identify the MTD of ADCT‐301 and provide a preliminary assessment of its single‐ agent anti‐tumor activity and toxicity profile in R/R HL and NHL. Dose escalation (part 1) is continuing. Further initial safety, tolerability, and efficacy results are expected later this year. http://clinicaltrials.gov/ show/NCT02432235